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Phase 2b Study to Evaluate the Efficacy and Safety of ISB 830 in Adults With Moderate to Severe Atopic Dermatitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03568162
Recruitment Status : Completed
First Posted : June 26, 2018
Results First Posted : June 28, 2022
Last Update Posted : August 23, 2022
Sponsor:
Collaborator:
Glenmark Pharmaceuticals S.A.
Information provided by (Responsible Party):
Ichnos Sciences SA

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Moderate to Severe Atopic Dermatitis
Interventions Drug: ISB 830 - Part 1 Group 1
Drug: ISB 830 - Part 1 Group 2
Drug: ISB 830 - Part 1 Group 3
Drug: Placebo - Part 1 Group 4
Drug: ISB 830 - Part 2 Group 5
Drug: Placebo - Part 2 Group 6
Enrollment 462
Recruitment Details The study was conducted in 4 phases: a Screening phase (28 days before randomization), a Blinded Treatment Phase (up to Week 16), an Open-label Treatment Phase (Week 16 to Week 54), and a Follow-up Phase (Week 54 to Week 66)
Pre-assignment Details During Blinded Treatment Phase, participants received placebo-controlled treatment with ISB 830 administered subcutaneously (SC) for 16 weeks at different dose levels. During the Open-label Treatment Phase, participants received treatment with ISB 830 administered SC every other week (q2w) for 38 weeks.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Period Title: Overall Study
Started 76 80 77 80 75 74
Completed 54 57 42 50 61 60
Not Completed 22 23 35 30 14 14
Reason Not Completed
Adverse Event             0             1             2             0             0             1
Death             0             0             0             0             1             0
Lost to Follow-up             3             2             4             2             3             2
Physician Decision             0             1             1             0             1             0
Pregnancy             0             0             0             1             0             0
Protocol Violation             1             0             1             1             1             1
Withdrawal by Subject             15             15             26             22             6             9
Others             3             4             1             4             2             1
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2 Total
Hide Arm/Group Description

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Total of all reporting groups
Overall Number of Baseline Participants 76 78 77 80 75 74 460
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Two participants randomized to ISB 830 300 mg q4w group discontinued study without receiving any study drug and were excluded from FAS.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
40.2  (13.10) 36.6  (14.77) 38.4  (16.87) 36.3  (13.05) 37.9  (13.31) 36.0  (13.75) 37.55  (14.21)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
Female
32
  42.1%
44
  56.4%
41
  53.2%
44
  55.0%
37
  49.3%
47
  63.5%
245
  53.3%
Male
44
  57.9%
34
  43.6%
36
  46.8%
36
  45.0%
38
  50.7%
27
  36.5%
215
  46.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
Hispanic or Latino
5
   6.6%
3
   3.8%
2
   2.6%
2
   2.5%
3
   4.0%
0
   0.0%
15
   3.3%
Not Hispanic or Latino
71
  93.4%
75
  96.2%
75
  97.4%
78
  97.5%
72
  96.0%
73
  98.6%
444
  96.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
5
   6.6%
4
   5.1%
4
   5.2%
7
   8.8%
2
   2.7%
1
   1.4%
23
   5.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
13
  17.1%
14
  17.9%
6
   7.8%
15
  18.8%
6
   8.0%
4
   5.4%
58
  12.6%
White
58
  76.3%
59
  75.6%
65
  84.4%
58
  72.5%
66
  88.0%
69
  93.2%
375
  81.5%
More than one race
0
   0.0%
1
   1.3%
2
   2.6%
0
   0.0%
0
   0.0%
0
   0.0%
3
   0.7%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
0
   0.0%
1
   0.2%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
28.72  (7.538) 27.49  (6.167) 26.32  (6.199) 27.20  (6.608) 26.03  (5.167) 26.50  (5.434) 27.05  (6.27)
Baseline Eczema Area and Severity Index (EASI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
30.42  (14.110) 33.84  (14.910) 28.42  (11.602) 30.65  (13.173) 29.86  (13.223) 31.81  (14.340) 30.84  (13.630)
[1]
Measure Description: In EASI, four disease characteristics of atopic dermatitis (AD) (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity. The EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Baseline Severity scoring of Atopic Dermatitis (SCORAD) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants 460 participants
67.50  (14.325) 69.09  (14.284) 66.22  (12.408) 66.12  (12.658) 66.40  (12.300) 67.66  (13.560) 67.16  (13.250)
[1]
Measure Description: SCORAD is a composite severity index score. A SCORAD score ranges from 0 (no AD present) to 103 (severe).
1.Primary Outcome
Title Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16
Hide Description In EASI, four disease characteristics of atopic dermatitis (AD) (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 51 45 39 42 53 51
Mean (Standard Deviation)
Unit of Measure: percentage change
-57.589  (36.2014) -56.734  (32.5395) -38.099  (39.6857) -42.142  (38.1945) -59.737  (27.1176) -43.252  (41.2404)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ISB 830 300 mg q2w, Placebo - 1
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The analysis was conducted using a mixed model for repeated measures (MMRM) model for percent change from baseline in EASI with the corresponding baseline value as covariate, and treatment group, region, disease severity, visit as fixed effect factors, and interactions of treatment-by-visit, baseline-by-visit
Statistical Test of Hypothesis P-Value = 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -20.192
Confidence Interval (2-Sided) 95%
-34.944 to 5.439
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.4781
Estimation Comments A linear contrast was used to estimate the treatment difference
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection ISB 830 300 mg q4w, Placebo - 1
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The analysis was conducted using a MMRM model for percent change from baseline in EASI with the corresponding baseline value as covariate, and treatment group, region, disease severity, visit as fixed effect factors, and interactions of treatment-by-visit, baseline-by-visit.
Statistical Test of Hypothesis P-Value = 0.061
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -14.439
Confidence Interval (2-Sided) 95%
-29.552 to 0.674
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.6622
Estimation Comments A linear contrast was used to estimate the treatment difference
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection ISB 830 75 mg q4w, Placebo - 1
Comments [Not Specified]
Type of Statistical Test Superiority
Comments The analysis was conducted using a mixed MMRM model for percent change from baseline in EASI with the corresponding baseline value as covariate, and treatment group, region, disease severity, visit as fixed effect factors, and interactions of treatment-by-visit, baseline-by-visit.
Statistical Test of Hypothesis P-Value = 0.691
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 3.144
Confidence Interval (2-Sided) 95%
-12.410 to 18.698
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.8864
Estimation Comments A linear contrast was used to estimate the treatment difference.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection ISB 830 600 mg q2w, Placebo - 2
Comments The analysis was conducted using a MMRM model for percent change from baseline in EASI with the corresponding baseline value as covariate, and treatment group, region, disease severity, visit as fixed effect factors, and interactions of treatment-by-visit, baseline-by-visit.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.008
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -17.199
Confidence Interval (2-Sided) 95%
-29.895 to -4.503
Parameter Dispersion
Type: Standard Error of the Mean
Value: 6.4090
Estimation Comments A linear contrast was used to estimate the treatment difference.
2.Secondary Outcome
Title Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16
Hide Description In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment, or withdrew before Week 16 was considered Non-responder.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Measure Type: Number
Unit of Measure: percentage of participants
23.7 20.5 11.7 11.3 25.3 18.9
3.Secondary Outcome
Title Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16
Hide Description The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment, or withdrew before Week 16 was considered Non-responder.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Measure Type: Number
Unit of Measure: percentage of participants
13.2 10.3 6.5 5.0 12.0 5.4
4.Secondary Outcome
Title Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16
Hide Description Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment or withdrew before Week 16 was considered Non-responder.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Measure Type: Number
Unit of Measure: percentage of participants
7.9 11.5 5.2 10.0 13.3 9.5
5.Secondary Outcome
Title Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16
Hide Description In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missing Week 16 assessment, or withdrew before Week 16 was considered Nonresponder
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Measure Type: Number
Unit of Measure: percentage of participants
48.7 34.6 27.3 27.5 44.0 33.8
6.Secondary Outcome
Title Percent Change From Baseline in SCORAD Score at Week 16
Hide Description SCORAD (Severity scoring of Atopic Dermatitis) is composite severity index comprising a) the amount/extent of BSA affected; b) subjective symptom visual analog assessments for pruritis ( 0 [no itching] to 3 [severe itching]) and sleep disturbance (0 [no sleep disturbance] to 3 [severe sleep disturbance]); and c) 6 disease intensity assessments [dryness/scaling, erythema, induration/papulation, excoriation, lichenification and oozing/weeping/crusting, each graded from 0 to (none) to 3 (severe). A SCORAD score ranges from 0 (no AD present) to 103 (severe).
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 51 45 39 42 53 51
Mean (Standard Deviation)
Unit of Measure: percentage change
-26.519  (18.1662) -26.108  (21.4476) -18.405  (15.8756) -19.440  (17.4296) -27.401  (14.4471) -18.847  (14.4472)
7.Secondary Outcome
Title Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Hide Description The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed at specified time point.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
15.2  (6.80) 15.4  (7.14) 14.3  (7.18) 14.3  (6.77) 14.1  (6.02) 14.7  (6.78)
Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
-7.3  (7.58) -6.7  (6.16) -4.1  (6.13) -4.7  (7.00) -6.6  (6.19) -5.5  (5.10)
8.Secondary Outcome
Title Change From Baseline in Global Individual Signs Score (GISS) at Week 16
Hide Description GISS assesses AD lesions for erythema, excoriations, lichenification and infiltration/papulation. Each component is rated on a global basis (over the entire body surface rather than region) using a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe) according to the EASI grading severity. Total score ranges from 0 to 12 (no disease to most severe disease, respectively).
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed at specified time point.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
9.1  (1.81) 9.4  (1.71) 9.1  (1.71) 8.9  (1.77) 9.0  (1.66) 8.9  (1.63)
Change at Week 16 Number Analyzed 51 participants 45 participants 39 participants 42 participants 53 participants 51 participants
-3.4  (2.52) -3.2  (2.81) -2.4  (2.52) -2.2  (2.49) -3.5  (2.52) -2.3  (2.21)
9.Secondary Outcome
Title Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16
Hide Description The HADS is a 14-item questionnaire, with 7 items related to anxiety (HADS-A) and 7 items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each subscale, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified category.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
HADS-A Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
6.1  (4.47) 6.1  (4.82) 6.1  (4.15) 6.2  (3.74) 6.0  (4.41) 6.7  (4.12)
HADS-D Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
4.3  (3.90) 4.8  (4.38) 4.9  (4.19) 4.2  (3.16) 4.7  (3.81) 5.0  (4.26)
HADS-A Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
-1.8  (3.34) -0.9  (3.54) -1.0  (3.16) -0.8  (3.39) -1.8  (3.80) -1.9  (3.85)
HADS-D Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
-1.1  (2.62) -1.0  (4.05) -0.6  (2.58) -0.1  (2.62) -0.9  (3.60) -1.2  (2.97)
10.Secondary Outcome
Title Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16
Hide Description The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema).
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified time point.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
20.2  (5.78) 20.9  (5.56) 19.8  (5.27) 21.2  (5.40) 20.7  (4.63) 21.1  (4.79)
Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
-7.1  (6.44) -4.8  (8.79) -3.8  (6.51) -5.0  (6.94) -7.0  (7.37) -5.5  (7.33)
11.Secondary Outcome
Title Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16
Hide Description For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: "Considering all the ways in which your disease affects you, indicate how well you are doing." Response choices were: "Poor"; "Fair"; "Good"; "Very Good"; "Excellent." For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: "How would you rate the way your disease responded to the study medication?" Response choices were: "Poor"; "Fair"; "Good"; "Very Good"; "Excellent".
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified category.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 76 78 77 80 75 74
Mean (Standard Deviation)
Unit of Measure: units on a scale
PGA of Disease Baseline Number Analyzed 76 participants 78 participants 77 participants 80 participants 75 participants 74 participants
2.0  (0.89) 1.9  (0.84) 2.1  (0.97) 1.9  (0.79) 2.0  (0.76) 2.1  (0.92)
PGA of Treatment Baseline Number Analyzed 70 participants 63 participants 65 participants 69 participants 67 participants 67 participants
2.1  (0.98) 2.0  (1.07) 2.1  (0.98) 2.0  (1.05) 2.2  (1.02) 1.9  (1.03)
PGA of Disease Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
1.1  (0.98) 1.2  (1.17) 0.8  (0.80) 1.1  (0.97) 1.1  (0.88) 0.8  (0.83)
PGA of Treatment Change at Week 16 Number Analyzed 50 participants 41 participants 37 participants 41 participants 52 participants 49 participants
0.9  (0.87) 1.1  (0.98) 0.7  (0.75) 0.7  (0.84) 1.0  (0.88) 0.7  (0.92)
12.Secondary Outcome
Title Percentage Change From Baseline in PGA of Disease and Treatment at Week 16
Hide Description For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: "Considering all the ways in which your disease affects you, indicate how well you are doing." Response choices were: "Poor"; "Fair"; "Good"; "Very Good"; "Excellent." For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: "How would you rate the way your disease responded to the study medication?" Response choices were: "Poor"; "Fair"; "Good"; "Very Good"; "Excellent".
Time Frame Baseline, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable for specified category.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 51 44 39 42 52 51
Mean (Standard Deviation)
Unit of Measure: percentage change
PGA of Disease: Percent Change at Week 16 Number Analyzed 51 participants 44 participants 39 participants 42 participants 52 participants 51 participants
72.2  (93.51) 73.3  (114.18) 33.3  (87.25) 76.2  (101.89) 69.2  (92.85) 40.4  (76.89)
PGA of Treatment: Percent Change at Week 16 Number Analyzed 50 participants 41 participants 37 participants 41 participants 52 participants 49 participants
42.3  (75.61) 50.6  (97.24) 16.0  (64.62) 21.3  (56.76) 55.0  (93.81) 15.2  (61.29)
13.Secondary Outcome
Title Number of Missed Work or School Days at Week 16
Hide Description Participants who were employed or enrolled in school were asked to report the number of sick leave and/or missed school days due to AD (eg, versus due to an accident) in the last 4 weeks.
Time Frame Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 44 35 31 32 34 38
Mean (Standard Deviation)
Unit of Measure: days
1.2  (3.73) 0.5  (0.92) 0.5  (1.26) 0.5  (1.29) 4.9  (14.92) 1.4  (5.31)
14.Secondary Outcome
Title Maximum Observed Serum Concentration (Cmax) of ISB 830
Hide Description Cmax is the maximum concentration of ISB 830 observed in serum
Time Frame Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), 4, 24, 96, 120, and 168 hours postdose on Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PKAS) included all participants who received at least 1 dose of ISB 830, did not had any major protocol deviation affecting pharmacokinetic (PK), and for whom at least 1 sample with detectable plasma concentration with known time of dosing and the time of sampling was available. 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w ISB 830 600 mg q2w
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 12 14 14 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliters (µg/mL)
Day 1 Number Analyzed 12 participants 14 participants 14 participants 3 participants
46.98
(46.5%)
49.95
(33.1%)
16.62
(32.6%)
92.84
(12.3%)
Day 85 Number Analyzed 11 participants 13 participants 10 participants 2 participants
52.33
(45.8%)
31.20
(60.4%)
8.8
(73.6%)
144.80
(6.8%)
15.Secondary Outcome
Title Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau)
Hide Description AUC0-tau is the area under the curve from time zero to the end of the dosing interval of ISB 830.
Time Frame Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), and at 4, 24, 96, 120, 168 hours postdose on Day 85
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Analysis Set (PKAS) included all participants who received at least 1 dose of ISB 830, did not had any major protocol deviation affecting pharmacokinetic (PK), and for whom at least 1 sample with detectable plasma concentration with known time of dosing and the time of sampling was available. 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w ISB 830 600 mg q2w
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 12 14 13 2
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*µg/mL
Day 1 Number Analyzed 12 participants 14 participants 13 participants 1 participants
12170
(49.9%)
20340
(34.1%)
6671
(40.2%)
26930
Day 85 Number Analyzed 10 participants 13 participants 7 participants 2 participants
12990
(40.3%)
13120
(49.5%)
3448
(97.8%)
39420
(2.6%)
16.Secondary Outcome
Title Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16
Hide Description Participants with ADA were those with at least 1 treatment-induced or treatment-boosted ADA-positive sample at any time during the treatment or follow-up observation period (up to Week 16). Treatment-emergent ADA referred to percentage of the total number of evaluable participants who were ADA-negative at baseline but developed ADA following biologic drug administration. Treatment-boosted ADA referred to percentage of the total number of evaluable participants who were ADA positive at baseline with at least 4-fold increase in ADA titer after biologic drug administration.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set (SAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment they received. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 ISB 830 600 mg q2w Placebo - 2
Hide Arm/Group Description:

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Overall Number of Participants Analyzed 75 77 77 79 75 74
Measure Type: Number
Unit of Measure: percentage of participants
13.3 29.9 50.6 5.1 10.7 6.8
Time Frame Up to Week 54
Adverse Event Reporting Description An adverse event (AE) is defined as any untoward medical occurrence and does not necessarily have to have causal relationship with the study medication. An AE can therefore be an unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease, which is a change from baseline and is temporally associated with the use of the study medication, whether or not it is considered related to the study medication
 
Arm/Group Title ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 (Blinded) Placebo - 1 (Open Label) ISB 830 600 mg q2w Placebo - 2 (Blinded) Placebo - 2 (Open Label)
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Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.

Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.

Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14. Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66.
All-Cause Mortality
ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 (Blinded) Placebo - 1 (Open Label) ISB 830 600 mg q2w Placebo - 2 (Blinded) Placebo - 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/76 (0.00%)   0/78 (0.00%)   0/77 (0.00%)   0/80 (0.00%)   0/60 (0.00%)   1/75 (1.33%)   0/74 (0.00%)   0/67 (0.00%) 
Hide Serious Adverse Events
ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 (Blinded) Placebo - 1 (Open Label) ISB 830 600 mg q2w Placebo - 2 (Blinded) Placebo - 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   4/76 (5.26%)   6/78 (7.69%)   4/77 (5.19%)   1/80 (1.25%)   2/60 (3.33%)   1/75 (1.33%)   0/74 (0.00%)   2/67 (2.99%) 
Blood and lymphatic system disorders                 
Pernicious anaemia  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Cardiac disorders                 
Atrial fibrillation  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eye disorders                 
Chorioretinopathy  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
General disorders                 
Eye complication associated with device  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Pyrexia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Infections and infestations                 
Viral infection  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Injury, poisoning and procedural complications                 
Gun shot wound  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Ligament rupture  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Femur fracture  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Metabolism and nutrition disorders                 
Metabolic acidosis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Keratoacanthoma  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Uterine leiomyoma  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Adenocarcinoma of colon  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Pregnancy, puerperium and perinatal conditions                 
Abortion spontaneous complete  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Skin and subcutaneous tissue disorders                 
Dermatitis atopic  1  2/76 (2.63%)  2/78 (2.56%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Vascular disorders                 
Hypertension  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
ISB 830 300 mg q2w ISB 830 300 mg q4w ISB 830 75 mg q4w Placebo - 1 (Blinded) Placebo - 1 (Open Label) ISB 830 600 mg q2w Placebo - 2 (Blinded) Placebo - 2 (Open Label)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   68/76 (89.47%)   56/78 (71.79%)   64/77 (83.12%)   57/80 (71.25%)   43/60 (71.67%)   65/75 (86.67%)   37/74 (50.00%)   38/67 (56.72%) 
Blood and lymphatic system disorders                 
Anaemia  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Blood loss anaemia  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Lymphadenopathy  1  0/76 (0.00%)  2/78 (2.56%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Lymphopenia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  2/80 (2.50%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Thrombocytosis  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Iron deficiency anaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Neutropenia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Cardiac disorders                 
Bradycardia  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tachycardia  1  0/76 (0.00%)  1/78 (1.28%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Ventricular extrasystoles  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Left ventricular hypertrophy  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Ear and labyrinth disorders                 
Deafness unilateral  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Ear pain  1  2/76 (2.63%)  0/78 (0.00%)  2/77 (2.60%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Ear swelling  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
External ear inflammation  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  2/80 (2.50%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Middle ear inflammation  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
External ear pain  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Endocrine disorders                 
Hypothyroidism  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Autoimmune thyroiditis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Eye disorders                 
Blepharitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Cataract  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Chalazion  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  2/80 (2.50%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Conjunctival hyperaemia  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Conjunctivitis allergic  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Eye haemorrhage  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eye irritation  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eyelid margin crusting  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eyelid oedema  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Keratitis  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Swelling of eyelid  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Photophobia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Visual impairment  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Gastrointestinal disorders                 
Diarrhoea  1  4/76 (5.26%)  2/78 (2.56%)  6/77 (7.79%)  1/80 (1.25%)  0/60 (0.00%)  3/75 (4.00%)  3/74 (4.05%)  1/67 (1.49%) 
Abdominal pain  1  1/76 (1.32%)  3/78 (3.85%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  4/75 (5.33%)  0/74 (0.00%)  0/67 (0.00%) 
Abdominal discomfort  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Abdominal pain upper  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Abdominal pain lower  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Aphthous ulcer  1  0/76 (0.00%)  2/78 (2.56%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Cheilitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Constipation  1  1/76 (1.32%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Dyspepsia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gastritis  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Gastrooesophageal reflux disease  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Haematochezia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Haemorrhoidal haemorrhage  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Haemorrhoids  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Nausea  1  3/76 (3.95%)  3/78 (3.85%)  2/77 (2.60%)  2/80 (2.50%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Odynophagia  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tooth impacted  1  2/76 (2.63%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Toothache  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Vomiting  1  1/76 (1.32%)  3/78 (3.85%)  1/77 (1.30%)  1/80 (1.25%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Dental caries  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Dry mouth  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Gastrointestinal inflammation  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Gastrooesophageal sphincter insufficiency  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Reflux gastritis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Stomatitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
General disorders                 
Fatigue  1  2/76 (2.63%)  5/78 (6.41%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Application site reaction  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Asthenia  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Chest pain  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Face oedema  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Facial pain  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Feeling cold  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Influenza like illness  1  1/76 (1.32%)  3/78 (3.85%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site bruising  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site erythema  1  1/76 (1.32%)  3/78 (3.85%)  0/77 (0.00%)  0/80 (0.00%)  2/60 (3.33%)  2/75 (2.67%)  1/74 (1.35%)  1/67 (1.49%) 
Injection site haematoma  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site induration  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site oedema  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site pain  1  1/76 (1.32%)  2/78 (2.56%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site pruritus  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site rash  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site reaction  1  0/76 (0.00%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Injection site swelling  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Injection site urticaria  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Oedema peripheral  1  1/76 (1.32%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Pain  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Peripheral swelling  1  2/76 (2.63%)  2/78 (2.56%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Pyrexia  1  2/76 (2.63%)  1/78 (1.28%)  2/77 (2.60%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  2/74 (2.70%)  0/67 (0.00%) 
Chest discomfort  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Chills  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Feeling hot  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Malaise  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Therapeutic response unexpected  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Hepatobiliary disorders                 
Hepatic function abnormal  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hepatic steatosis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hypertransaminasaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Immune system disorders                 
Allergy to animal  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Allergy to arthropod sting  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Drug hypersensitivity  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Food allergy  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hypersensitivity  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Seasonal allergy  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Allergy to arthropod bite  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Infections and infestations                 
Influenza  1  4/76 (5.26%)  5/78 (6.41%)  1/77 (1.30%)  0/80 (0.00%)  2/60 (3.33%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Nasopharyngitis  1  16/76 (21.05%)  15/78 (19.23%)  10/77 (12.99%)  7/80 (8.75%)  9/60 (15.00%)  12/75 (16.00%)  7/74 (9.46%)  8/67 (11.94%) 
Oral herpes  1  2/76 (2.63%)  3/78 (3.85%)  6/77 (7.79%)  2/80 (2.50%)  4/60 (6.67%)  2/75 (2.67%)  2/74 (2.70%)  3/67 (4.48%) 
Sinusitis  1  0/76 (0.00%)  1/78 (1.28%)  2/77 (2.60%)  0/80 (0.00%)  3/60 (5.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Upper respiratory tract infection  1  12/76 (15.79%)  8/78 (10.26%)  13/77 (16.88%)  4/80 (5.00%)  8/60 (13.33%)  6/75 (8.00%)  5/74 (6.76%)  1/67 (1.49%) 
Urinary tract infection  1  3/76 (3.95%)  4/78 (5.13%)  4/77 (5.19%)  4/80 (5.00%)  4/60 (6.67%)  3/75 (4.00%)  2/74 (2.70%)  1/67 (1.49%) 
Bronchitis  1  1/76 (1.32%)  0/78 (0.00%)  3/77 (3.90%)  0/80 (0.00%)  1/60 (1.67%)  4/75 (5.33%)  0/74 (0.00%)  0/67 (0.00%) 
Abscess limb  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Abscess oral  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Acarodermatitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Asymptomatic bacteriuria  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Bacterial blepharitis  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Bacterial vaginosis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Cellulitis  1  1/76 (1.32%)  1/78 (1.28%)  1/77 (1.30%)  1/80 (1.25%)  1/60 (1.67%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Chest wall abscess  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Chronic sinusitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Conjunctivitis  1  2/76 (2.63%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  2/75 (2.67%)  1/74 (1.35%)  1/67 (1.49%) 
Conjunctivitis bacterial  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Ear infection  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Ear lobe infection  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eczema herpeticum  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eczema impetiginous  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Enteritis infectious  1  0/76 (0.00%)  2/78 (2.56%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Eyelid infection  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Folliculitis  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  2/80 (2.50%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Furuncle  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gastroenteritis  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  1/67 (1.49%) 
Gastroenteritis viral  1  0/76 (0.00%)  2/78 (2.56%)  1/77 (1.30%)  0/80 (0.00%)  2/60 (3.33%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gastrointestinal infection  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gastrointestinal viral infection  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  2/80 (2.50%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gingivitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Herpes ophthalmic  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Herpes simplex  1  0/76 (0.00%)  1/78 (1.28%)  3/77 (3.90%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Herpes zoster  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hordeolum  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Impetigo  1  2/76 (2.63%)  0/78 (0.00%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  3/75 (4.00%)  0/74 (0.00%)  0/67 (0.00%) 
Laryngitis  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  2/60 (3.33%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Localised infection  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Ophthalmic herpes simplex  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Oral candidiasis  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Otitis externa  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Otitis externa bacterial  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Paronychia  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Peritonsillar abscess  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Pharyngitis  1  0/76 (0.00%)  2/78 (2.56%)  0/77 (0.00%)  2/80 (2.50%)  1/60 (1.67%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Pharyngitis streptococcal  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Pulpitis dental  1  3/76 (3.95%)  0/78 (0.00%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Pyuria  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Respiratory tract infection  1  2/76 (2.63%)  2/78 (2.56%)  1/77 (1.30%)  2/80 (2.50%)  1/60 (1.67%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Rhinitis  1  0/76 (0.00%)  2/78 (2.56%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Skin bacterial infection  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Skin candida  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Skin infection  1  2/76 (2.63%)  2/78 (2.56%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Staphylococcal infection  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Staphylococcal skin infection  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Subcutaneous abscess  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Superinfection  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Superinfection bacterial  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tinea pedis  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Tonsillitis  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  1/67 (1.49%) 
Tooth abscess  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Trichomoniasis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Varicella zoster virus infection  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Viral infection  1  1/76 (1.32%)  2/78 (2.56%)  0/77 (0.00%)  1/80 (1.25%)  2/60 (3.33%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Viral pharyngitis  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Viral upper respiratory tract infection  1  3/76 (3.95%)  1/78 (1.28%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Vulvovaginal candidiasis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Vulvovaginal mycotic infection  1  1/76 (1.32%)  1/78 (1.28%)  1/77 (1.30%)  2/80 (2.50%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Acne pustular  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Asymptomatic COVID-19  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Bacterial vulvovaginitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Bacteriuria  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
COVID-19  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  1/67 (1.49%) 
Cystitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Eczema infected  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Enterobiasis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Epiglottitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Erysipelas  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Genital herpes  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Genital infection female  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Infection  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Periodontitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Pneumonia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Rash pustular  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Testicular abscess  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Tooth infection  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Vaginal infection  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  2/67 (2.99%) 
Injury, poisoning and procedural complications                 
Accidental overdose  1  0/76 (0.00%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Alcohol poisoning  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Arthropod bite  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  3/75 (4.00%)  0/74 (0.00%)  0/67 (0.00%) 
Burns second degree  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Contusion  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Epicondylitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hand fracture  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Injection related reaction  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Ligament sprain  1  0/76 (0.00%)  1/78 (1.28%)  2/77 (2.60%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Limb injury  1  3/76 (3.95%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Meniscus injury  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Muscle strain  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Overdose  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Procedural pain  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Rib fracture  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Road traffic accident  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Skin abrasion  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Skin laceration  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tooth fracture  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Joint injury  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  3/67 (4.48%) 
Ligament injury  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Nail injury  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Transfusion related complication  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Vaccination complication  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Wrist fracture  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Investigations                 
Alanine aminotransferase increased  1  0/76 (0.00%)  2/78 (2.56%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Bacterial test positive  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Blood bicarbonate decreased  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Blood creatinine increased  1  1/76 (1.32%)  0/78 (0.00%)  2/77 (2.60%)  1/80 (1.25%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Blood glucose increased  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Blood pressure increased  1  2/76 (2.63%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Blood triglycerides increased  1  2/76 (2.63%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Blood urine present  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Body temperature increased  1  0/76 (0.00%)  2/78 (2.56%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
C-reactive protein increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Cardiac murmur  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Glucose urine present  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hepatic enzyme increased  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Lymphocyte count decreased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Neutrophil count decreased  1  0/76 (0.00%)  2/78 (2.56%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Red blood cells urine positive  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Streptococcus test positive  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Urinary casts present  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Urine leukocyte esterase positive  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Weight increased  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
White blood cell count increased  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  2/74 (2.70%)  0/67 (0.00%) 
Aspartate aminotransferase increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Blood bilirubin increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Blood iron decreased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Gamma-glutamyltransferase increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Haemoglobin decreased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Haemoglobin urine present  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Liver function test increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Platelet count increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Protein urine present  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Red blood cell count decreased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Transaminases increased  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Urine ketone body present  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
White blood cells urine positive  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Metabolism and nutrition disorders                 
Dehydration  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Diabetes mellitus  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Dyslipidaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Gout  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Histamine intolerance  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hyperglycaemia  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hyperlipidaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  1/60 (1.67%)  2/75 (2.67%)  0/74 (0.00%)  1/67 (1.49%) 
Hypertriglyceridaemia  1  2/76 (2.63%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Hypokalaemia  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Increased appetite  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Vitamin B12 deficiency  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Hypercholesterolaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Hyperkalaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Hyperuricaemia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Vitamin D deficiency  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Musculoskeletal and connective tissue disorders                 
Arthralgia  1  6/76 (7.89%)  2/78 (2.56%)  4/77 (5.19%)  0/80 (0.00%)  3/60 (5.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Back pain  1  3/76 (3.95%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  1/67 (1.49%) 
Groin pain  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Joint swelling  1  0/76 (0.00%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Ligamentitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Muscle spasms  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Musculoskeletal stiffness  1  2/76 (2.63%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Myalgia  1  1/76 (1.32%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  1/67 (1.49%) 
Pain in extremity  1  0/76 (0.00%)  0/78 (0.00%)  2/77 (2.60%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Pain in jaw  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Scleroderma  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Spinal pain  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  2/80 (2.50%)  1/60 (1.67%)  0/75 (0.00%)  1/74 (1.35%)  1/67 (1.49%) 
Synovitis  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tendonitis  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Arthritis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Bursitis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Muscle tightness  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Musculoskeletal discomfort  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Musculoskeletal pain  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Neck pain  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  2/75 (2.67%)  0/74 (0.00%)  0/67 (0.00%) 
Spinal osteoarthritis  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  1/74 (1.35%)  0/67 (0.00%) 
Tendon pain  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                 
Uterine leiomyoma  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Benign breast neoplasm  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  1/67 (1.49%) 
Skin papilloma  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  0/74 (0.00%)  0/67 (0.00%) 
Nervous system disorders                 
Headache  1  8/76 (10.53%)  7/78 (8.97%)  4/77 (5.19%)  8/80 (10.00%)  5/60 (8.33%)  6/75 (8.00%)  5/74 (6.76%)  7/67 (10.45%) 
Aphonia  1  0/76 (0.00%)  0/78 (0.00%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Dizziness  1  2/76 (2.63%)  2/78 (2.56%)  2/77 (2.60%)  0/80 (0.00%)  1/60 (1.67%)  0/75 (0.00%)  2/74 (2.70%)  1/67 (1.49%) 
Dysaesthesia  1  1/76 (1.32%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Loss of consciousness  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Migraine  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Nerve compression  1  0/76 (0.00%)  0/78 (0.00%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Paraesthesia  1  0/76 (0.00%)  0/78 (0.00%)  2/77 (2.60%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Presyncope  1  0/76 (0.00%)  1/78 (1.28%)  0/77 (0.00%)  1/80 (1.25%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Sciatica  1  0/76 (0.00%)  1/78 (1.28%)  1/77 (1.30%)  0/80 (0.00%)  0/60 (0.00%)  1/75 (1.33%)  1/74 (1.35%)  0/67 (0.00%) 
Sinus headache  1  1/76 (1.32%)  0/78 (0.00%)  0/77 (0.00%)  0/80 (0.00%)  0/60 (0.00%)  0/75 (0.00%)  0/74 (0.00%)  0/67 (0.00%) 
Tension headache  1