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Trial record 11 of 29 for:    LY2439821

A Phase 3 Study in Participants With Moderate to Severe Psoriasis (UNCOVER-2) (UNCOVER-2)

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: NCT01597245
Recruitment Status : Active, not recruiting
First Posted : May 14, 2012
Results First Posted : October 20, 2016
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Psoriasis
Interventions Drug: 80 mg ixekizumab Dosing Regimen
Drug: 50 mg etanercept
Drug: Placebo
Enrollment 1224
Recruitment Details  
Pre-assignment Details Participants who received ixekizumab (ixe) and classified as responder (Resp, sPGA 0/1) in Induction (IND) re-randomized to receive 80 mg ixe Q4W, Q12W or placebo (PBO) in Maintenance (MAIN) (Primary Population [Pop]). Non-responders (Non-Resp, sPGA >1) in IND received 80 mg ixe Q4W, PBO Resp, ETN Resp received PBO in MAIN (Secondary Pop).
Arm/Group Title Placebo- Induction Period 50 mg Etanercept (ETN) - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period Ixe/Placebo- Maintenance Period Primary Pop Ixe/Ixe Q12W - Maintenance Period Primary Pop Ixe/Ixe Q4W - Maintenance Period Primary Pop Placebo Resp/Placebo - Maintenance Period Secondary Pop Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop ETN Resp/Placebo Maintenance Period Secondary Pop ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop Ixe Q2W Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop
Hide Arm/Group Description Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12. 50 milligrams (mg) ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10). 160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W:Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12. 160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12 Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56. To maintain blinding with Q4W dose regimen, Placebo for ixe given as 1 SC injection at every 4 weeks from Week 16 through Week 56. Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received placebo during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received placebo in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received ETN during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received ETN in Induction Period (Weeks 0 to 12) and classified as non-responders were administered 2 SC injections of placebo at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q4W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q2W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.
Period Title: Induction Period (Week 0 - Week 12)
Started 168 358 347 351 0 0 0 0 0 0 0 0 0
Received at Least 1 Dose of Study Drug 167 357 347 350 0 0 0 0 0 0 0 0 0
Completed 158 333 [1] 328 342 [2] 0 0 0 0 0 0 0 0 0
Not Completed 10 25 19 9 0 0 0 0 0 0 0 0 0
Reason Not Completed
Adverse Event             1             5             5             4             0             0             0             0             0             0             0             0             0
Withdrawal by Subject             2             8             6             2             0             0             0             0             0             0             0             0             0
Protocol Violation             2             4             5             2             0             0             0             0             0             0             0             0             0
Lost to Follow-up             1             5             2             0             0             0             0             0             0             0             0             0             0
Physician Decision             1             0             0             1             0             0             0             0             0             0             0             0             0
Lack of Efficacy             3             3             1             0             0             0             0             0             0             0             0             0             0
[1]
1 participant randomized to maintenance period but did not receive a dose in the maintenance period.
[2]
2 participants discontinued after IND completion and prior to randomizing into maintenance period.
Period Title: Maintenance Period (Week 12 to Week 60)
Started 0 0 0 0 176 181 187 3 155 132 200 75 49
Participants Received One Dose 0 0 0 0 176 181 187 3 155 132 200 75 49
Completed 0 0 0 0 17 92 150 0 135 14 178 56 37
Not Completed 0 0 0 0 159 89 37 3 20 118 22 19 12
Reason Not Completed
On study treatment             0             0             0             0             0             1             1             0             0             0             0             0             0
Relapsed             0             0             0             0             148             80             21             2             0             111             0             0             0
Lack of Efficacy             0             0             0             0             0             0             1             0             3             0             2             10             4
Adverse Event             0             0             0             0             4             6             6             1             8             2             8             1             2
Withdrawal by Subject             0             0             0             0             3             1             3             0             4             1             6             5             4
Protocol Violation             0             0             0             0             1             0             0             0             3             1             2             0             1
Lost to Follow-up             0             0             0             0             3             1             4             0             1             2             2             2             1
Physician Decision             0             0             0             0             0             0             1             0             1             1             1             1             0
Sponsor Decision             0             0             0             0             0             0             0             0             0             0             1             0             0
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period Total
Hide Arm/Group Description Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12. 50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10). 160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W: Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12. 160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12. Total of all reporting groups
Overall Number of Baseline Participants 168 358 347 351 1224
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
45.3  (12.13) 45.3  (12.79) 45  (13.53) 44.5  (13.27) 45.0  (13.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
Female
48
  28.6%
122
  34.1%
103
  29.7%
130
  37.0%
403
  32.9%
Male
120
  71.4%
236
  65.9%
244
  70.3%
221
  63.0%
821
  67.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
Hispanic or Latino
11
   6.5%
26
   7.3%
24
   6.9%
19
   5.4%
80
   6.5%
Not Hispanic or Latino
130
  77.4%
279
  77.9%
271
  78.1%
274
  78.1%
954
  77.9%
Unknown or Not Reported
27
  16.1%
53
  14.8%
52
  15.0%
58
  16.5%
190
  15.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
American Indian or Alaska Native
2
   1.2%
0
   0.0%
2
   0.6%
2
   0.6%
6
   0.5%
Asian
6
   3.6%
8
   2.2%
11
   3.2%
12
   3.4%
37
   3.0%
Native Hawaiian or Other Pacific Islander
1
   0.6%
1
   0.3%
1
   0.3%
0
   0.0%
3
   0.2%
Black or African American
10
   6.0%
13
   3.6%
11
   3.2%
5
   1.4%
39
   3.2%
White
149
  88.7%
331
  92.5%
315
  90.8%
330
  94.0%
1125
  91.9%
More than one race
0
   0.0%
1
   0.3%
3
   0.9%
1
   0.3%
5
   0.4%
Unknown or Not Reported
0
   0.0%
4
   1.1%
4
   1.2%
1
   0.3%
9
   0.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
Canada 40 82 82 84 288
Austria 2 10 6 5 23
Netherlands 1 2 2 1 6
Czech Republic 3 6 3 6 18
Romania 6 9 8 12 35
United States 49 111 105 104 369
Poland 14 30 28 30 102
United Kingdom 4 9 9 11 33
Australia 7 13 15 16 51
France 7 18 21 19 65
Germany 28 53 51 47 179
Spain 7 15 17 16 55
Baseline in Static Physician Global Assessment (sPGA)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
sPGA = 3 86 186 166 178 616
sPGA = 4,5 82 172 181 173 608
[1]
Measure Description: The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. The sPGA is recommended as an endpoint to use to assess efficacy in the treatment of Ps (EMEA 2004). Overall lesions are categorized by descriptions for induration, erythema, and scaling. For the analysis of responses, the participant's Ps is assessed at a given time point on a 6-point scale in which 0 = cleared, 1 = minimal, 2 = mild, 3 = moderate; 4 = severe, 5 = very severe.
Baseline in Participants Achieving Psoriasis Area and Severity Index (PASI) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
20.57  (8.366) 19.07  (6.701) 20.04  (6.962) 19.35  (7.339) 19.63  (7.216)
[1]
Measure Description: PASI is another accepted primary efficacy measurement for this phase of development of Ps treatments. The PASI combines assessments of the extent of body-surface involvement in 4 anatomical regions (head, trunk, arms, and legs) and the severity of desquamation, erythema, and plaque induration/infiltration (thickness) in each region, yielding an overall score of 0 or no Ps to 72 for the most severe disease.
Baseline Dermatology-Specific Quality of Life Index (DLQI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
12.8  (7.24) 12.7  (7.03) 11.6  (6.65) 12.4  (6.86) 12.3  (6.91)
[1]
Measure Description: DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much) and unanswered ("not relevant") responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life impairment.
Baseline in Nail Psoriasis Severity Index (NAPSI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
27.62  (20.937) 30.44  (20.648) 23.70  (18.696) 26.27  (20.388) 26.97  (20.211)
[1]
Measure Description: The NAPSI scale evaluates Ps severity in the fingernail bed and fingernail matrix with each divided into quadrants. Scores range from 0 (none) to 4 (Ps in all 4 quadrants), depending on the presence (score of 1) or absence (score of 0) of Ps in each quadrant of the fingernail bed or matrix. NAPSI score of a fingernail is the sum of scores from each quadrant of the fingernail bed and fingernail matrix (maximum of 8). The total NAPSI score equals the sum of all fingernails and ranges from 0 to 80. Higher scores indicate more severe Ps.
Baseline in Psoriasis Scalp Severity Index (PSSI) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
21.0  (15.24) 20.0  (15.19) 20.8  (15.63) 19.5  (14.85) 20.2  (15.22)
[1]
Measure Description: The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total score ranging from 0 (less severity) to 72 (more severity).
Baseline in Body Surface Area (BSA) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
27.2  (18.12) 25.3  (15.50) 27.0  (17.23) 25.1  (15.82) 26.0  (16.47)
[1]
Measure Description: BSA is a physician rating of the percentage of involvement of Ps for each participant. BSA is assessed on a continuous scale from 0% (no involvement) to 100% (full involvement), where 1% corresponds to the size of the participant's hand (includes the palm, fingers and thumb). Total BSA is the sum of handprints from the affected areas.
Baseline in Quick Inventory of Depressive Symptomatology Self Report 16 items (QIDS-SR16) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
4.7  (4.14) 4.5  (4.07) 4.4  (4.04) 4.6  (3.84) 4.5  (4.00)
[1]
Measure Description: QIDS-SR16 is a participant-administered, 16-item instrument assesses the existence and severity of symptoms of depression. A participant is asked a statement relating to the way they have felt for the past 7 days and rate on a 4-point scale: 0 (best) to 3 (worst). The sum of the domains [sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite/weight, and psychomotor agitation/retardation] to give a single total scores range from 0 to 27, with higher scores indicating greater symptom severity.
Baseline in Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
Absenteeism Score (n=106, 227, 232, 238, 803) 4.3  (16.61) 3.7  (15.24) 4.6  (17.65) 7.3  (22.15) 5.1  (18.40)
Active Impairment Score (n=166,356,346,347,1215) 30.2  (28.87) 31.3  (29.04) 29.4  (29.28) 31.7  (29.64) 30.7  (29.24)
Presenteeism Score (n=109, 239, 243,248, 839) 24.3  (26.19) 21.2  (25.42) 22.3  (24.77) 24.2  (25.80) 22.8  (25.44)
Work Productivity Loss (n=105,227,231,237,800) 26.1  (28.11) 22.3  (26.52) 24.6  (27.41) 27.7  (29.19) 25.0  (27.82)
[1]
Measure Description: The (WPAI-PSO) is a 6-item instrument to assess the impact of psoriasis on productivity impairment within the past 7 days and has four domains: absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as each score * 100 and ranges from 0-100; greater scores indicate greater impairment.
Baseline in Short form (36 Items) Health Survey SF-36 Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
Physical Summary Score (n=166,354,345,350,1215) 47.7094  (9.5043) 47.5268  (9.0729) 47.6231  (8.9693) 47.6996  (9.0332) 47.6289  (9.0814)
Mental Summary Score (n=166, 354, 345, 350, 1215) 47.7889  (10.6183) 48.7097  (10.6546) 49.0131  (10.9087) 47.7140  (11.6686) 48.3832  (11.0234)
[1]
Measure Description: The SF-36 is a self-reported instrument that measures the participant's health status during the previous 7 days. It comprises 36-items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped in the Physical Component Score (PCS) and Mental Component Score (MCS) scores. Scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.
Baseline in Patient's Global Assessment (PatGA) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 168 participants 358 participants 347 participants 351 participants 1224 participants
4.0  (0.92) 4.0  (0.96) 4.1  (0.90) 4.1  (0.91) 4.0  (0.92)
[1]
Measure Description: The PatGA is a single-item self-reported instrument asking the participant to rate the severity of their psoriasis "today" by circling a number on the numeric rating scale from 0 (Clear = no psoriasis) to 5 (Severe = the worst their psoriasis has ever been).
1.Primary Outcome
Title Percentage of Participants With a Static Physician Global Assessment (sPGA) of (0,1) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: Static Physician Global Assessment [sPGA])
Hide Description The sPGA is the physician's determination of the participant's Psoriasis (Ps) lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe). An sPGA responder was defined as having a post-baseline sPGA score of “0” or “1” with at least a 2-point improvement from baseline.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Arm/Group Title Placebo - Induction Period 50 mg Etanercept (ETN) - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections Q2W up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W: Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 168 358 347 351
Measure Type: Number
Unit of Measure: percentage of participants
2.4 36.0 72.9 83.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg Etanercept (ETN) - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants Achieving Psoriasis Area and Severity Index (PASI) ≥75% (PASI75) Improvement (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: Psoriasis Area and Severity Index [PASI])
Hide Description The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored separately and the scores then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI75 were defined as having an improvement of ≥75% in the PASI score compared to baseline.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 168 358 347 351
Measure Type: Number
Unit of Measure: percentage of participants
2.4 41.6 77.5 89.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants Achieving an sPGA (0) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [sPGA])
Hide Description The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant’s Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections Q2W up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W: Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 168 358 347 351
Measure Type: Number
Unit of Measure: percentage of participants
0.6 5.9 32.3 41.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants Achieving PASI 90% (PASI90) (Efficacy of Ixekizumab in Participants With Moderate to Severe Chronic Plaque Psoriasis. Measure: [PASI])
Hide Description The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI90 were defined as having an improvement of ≥90% in the PASI score compared to baseline.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they were assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 168 358 347 351
Measure Type: Number
Unit of Measure: percentage of participants
0.6 18.7 59.7 70.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants Achieving PASI 100% (PASI100)
Hide Description The PASI combines the extent of body surface involvement in 4 anatomical regions (head, trunk, arms, and legs). For each region the percent area of skin involved was estimated from 0 (0%) to 6 (90%-100%) and severity was estimated by clinical signs of erythema, induration and scaling with a scores range from 0 (no involvement) to 4 (severe involvement). Each area is scored by itself and the scores were then combined for the final PASI. Final PASI calculated as: sum of severity parameters for each region * area score * weighing factor (head [0.1], upper limbs [0.2], trunk [0.3], lower limbs [0.4]). Overall scores range from 0 (no Ps) to 72 (the most severe disease). Participants achieving PASI100 were defined as having an improvement of 100% in the PASI score compared to baseline.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 168 358 347 351
Measure Type: Number
Unit of Measure: percentage of participants
0.6 5.3 30.8 40.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Maintaining an sPGA (0,1) From Week 12 After Re-randomization at Start of Maintenance Dosing Period to Week 60
Hide Description The sPGA is the physician's determination of the participant's Ps lesions overall at a given time point. Lesions were categorized by descriptions for induration, erythema, and scaling. Participant's Ps was assessed as 0 (clear), 1 (minimal), 2 (mild), 3 (moderate), 4 (severe), or 5 (very severe).
Time Frame Week 60
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who had sPGA score of (0,1) at Week 12, were re-randomized at Week 12 and received at least 1 dose of study treatment in the Maintenance Dosing Period. Participants who did not meet the clinical response criteria or had missing data at Week 60 were considered non-responders for Non-Responder Imputation (NRI) analysis.
Arm/Group Title Ixe/Placebo- Maintenance Period Primary Pop Ixe/Ixe Q12W - Maintenance Period Primary Pop Ixe/Ixe Q4W - Maintenance Period Primary Pop
Hide Arm/Group Description:
Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56.
Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56. To maintain blinding with Q4W dose regimen, placebo for ixe given as 1 SC injection at every 4 weeks from Week 16 through Week 56 .
Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56.
Overall Number of Participants Analyzed 176 181 187
Measure Type: Number
Unit of Measure: Percentage of participants
6.3 40.9 74.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ixe/Placebo- Maintenance Period Primary Pop, Ixe/Ixe Q12W - Maintenance Period Primary Pop
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ixe/Placebo- Maintenance Period Primary Pop, Ixe/Ixe Q4W - Maintenance Period Primary Pop
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
7.Secondary Outcome
Title Percentage of Participants With Itching Severity (Itch Numeric Rating Scale [NRI]) Score ≥4 Point Reduction From Baseline
Hide Description The Itch Numeric Rating Scale (NRS) is a participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no itch" and 10 representing "worst itch imaginable". The number and percentage of participants achieving an Itch NRS ≥4 point reduction from baseline were presented by treatment group for participants who had a baseline Itch NRS ≥4. Describes worst level of itching in past 24 hours.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned and had Itch NRS ≥4 at baseline. Participants who did not meet the clinical response criteria or had missing data at Week 12 were considered non-responders for NRI analysis.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 135 306 293 303
Measure Type: Number
Unit of Measure: percentage of participants
14.1 57.8 76.8 85.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Dermatology-Specific Quality of Life Index (DLQI) Total Score (Quality of Life and Outcome Assessments. Measures: Participant Reported Outcomes [PRO])
Hide Description DLQI is a participant-administered, 10-question, validated, quality-of-life questionnaire that covers 6 domains, including symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Response categories include 0 (not at all), 1 (a little), 2 (a lot), and 3 (very much); and "not relevant" and unanswered responses were scored as "0." Total scores range from 0 to 30, with higher score indicating greater quality of life impairment. A 5-point change from baseline is considered clinically relevant. Least Squares (LS) Mean change from baseline was calculated using mixed model repeated measures (MMRM) with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned and who had baseline and at least 1 post-baseline DLQI measurement.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 160 346 338 343
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-2.0  (0.36) -7.7  (0.25) -9.4  (0.25) -10.4  (0.25)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline in Nail Psoriasis Severity Index (NAPSI)
Hide Description The NAPSI scale is used to evaluate the severity of fingernail bed Ps and fingernail matrix Ps. The fingernail bed and fingernail matrix are each divided into quadrants. Each fingernail is given a score for fingernail bed Ps and fingernail matrix Ps, each with scores of 0 (none) to 4 (Ps in all 4 quadrants), depending on the presence (score of 1) or absence (score of 0) of Ps in each quadrant of the fingernail bed or matrix. The NAPSI score of a fingernail is the sum of scores from each quadrant of the fingernail bed and fingernail matrix (maximum of 8). The total NAPSI score equals the sum of all fingernails and ranges from 0 to 80 with higher scores indicating more severe Ps. LS mean change from baseline in NAPSI score was calculated using MMRM with baseline score as covariate, treatment, pooled center, visit and treatment-by-visit interaction as fixed effects.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned; and had fingernail Ps involvement at baseline and at least 1 post-baseline NAPSI measurement.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 111 219 215 206
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.82  (1.162) -5.34  (0.835) -7.39  (0.843) -8.60  (0.853)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline Psoriasis Scalp Severity Index (PSSI) Score
Hide Description The PSSI is a physician assessment of erythema, induration and desquamation and percent of scalp that is covered with a scores range from 0 (none) to 4 (very severe). The composite score is derived from the sum of scores for erythema, induration, and desquamation multiplied by the score recorded for the extent of the scalp area involved, 1 (<10%) to 6 (90%-100%) with a total scores range from 0 (less severity) to 72 (more severity), with lower scores indicating less severity. LS mean change from baseline in PSSI score was calculated using MMRM with baseline score as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned; and had scalp Ps involvement at baseline and at least 1 post-baseline PSSI measurement. Missing data was imputed by last observation carried forward (LOCF).
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 150 316 307 318
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.8  (0.73) -14.8  (0.50) -18.5  (0.51) -18.7  (0.50)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in Percent of Body Surface Area (BSA) Involvement of Psoriasis
Hide Description The percentage involvement of psoriasis on each participant's body surface area was assessed by the investigator on a continuous scale from 0% (no involvement) to 100% (full involvement), in which 1% corresponds to the size of the participant's hand including palm, fingers and thumb. LS mean change from baseline in BSA was calculated using MMRM with baseline BSA as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned; and had at least 1 post-baseline BSA measurement.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 166 350 342 348
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.5  (1.05) -12.4  (0.72) -20.3  (0.72) -20.6  (0.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
12.Secondary Outcome
Title Change From Baseline in Quick Inventory of Depressive Symptomatology-Self Report 16 Items (QIDS-SR16) Total Score
Hide Description The QIDS-SR16 is a self-administered, 16-item instrument in which a participant is asked to consider each statement as it relates to the way they have felt for the past 7 days. There is a 4-point scale for each item ranging from 0 (best) to 3 (worst). The 16 items are scored to give 9 individual depression domains (sad mood, concentration, self-criticism, suicidal ideation, interest, energy/fatigue, sleep disturbance [initial, middle and late insomnia or hypersomnia], decrease/increase in appetite/weight, and psychomotor agitation/retardation), which are summed to give a single score ranging from 0 to 27, with higher scores denoting greater symptom severity. LS mean change from baseline in total QIDS-SR16 score was calculated using the analysis of covariance (ANCOVA) model with treatment, pooled center and baseline QIDS total score.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned, and had baseline and at least 1 post baseline QIDS-SR16 measurement. Missing data was imputed by last observation carried forward (LOCF).
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 162 342 334 347
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.1  (0.21) -0.3  (0.15) -0.7  (0.15) -0.9  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.150
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
13.Secondary Outcome
Title Change From Baseline in All Scores of the Work Productivity Activity Impairment Questionnaire-Psoriasis (WPAI-PSO)
Hide Description The (WPAI-PSO) is a 6-item instrument used to assess the impact of psoriasis on productivity impairment within the past 7 days and has four domains, namely, absenteeism, presenteeism (reduced productivity while at work), an overall work impairment score, and impairment in daily activities performed outside of work. Four scores are derived as percentages: absenteeism, presenteeism, overall work impairment (absenteeism and presenteeism), and impairment in activities performed outside of work. Percentage is calculated as each score * 100 and ranges from 0 to 100; greater scores indicate greater impairment. LS mean change from baseline in each WPAI-PSO score was calculated using the (ANCOVA) model with treatment, pooled center and baseline WPAI value.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned, and had baseline and at least 1 post baseline WPAI-PSO measurement. Missing data was imputed by last observation carried forward ( LOCF ).
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 160 342 332 340
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Absenteeism (n=87, 199, 204, 213) -1.5  (0.83) -3.7  (0.55) -3.2  (0.54) -3.9  (0.54)
Activity Impairment Score (n=160, 342, 332, 340) -0.4  (1.46) -16.6  (1.00) -22.6  (1.02) -25.8  (1.01)
Presenteeism Score (n=94, 217, 226, 232) -2.4  (1.59) -12.4  (1.05) -18.5  (1.03) -18.2  (1.03)
Work Productivity Loss Score (n=86, 199, 203, 211) -2.0  (1.80) -13.7  (1.18) -19.3  (1.18) -19.5  (1.18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Absenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Absenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Absenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.016
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Activity Impairment Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Activity Impairment Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Activity Impairment Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Presenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Presenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Presenteeism Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Work Productivity Loss Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Work Productivity Loss Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Work Productivity Loss Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
14.Secondary Outcome
Title Change From Baseline in Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores
Hide Description The SF-36 is a participant-reported outcome measure evaluating participant's health status. It comprises 36 items covering 8 domains: physical functioning, role physical, role emotional, bodily pain, vitality, social functioning, mental health, and general health. Items are answered on Likert scales of varying lengths. The 8 domains are regrouped into the PCS and MCS scores. The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health. In this study, the SF-36 acute version was used, which has a 1 week recall period. LS mean change from baseline in SF-36 score was calculated using the ANCOVA model with treatment, pooled center and baseline SF-36 score.
Time Frame Baseline, Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned, and had baseline and at least 1 post baseline SF-36 measurement. Missing data was imputed by last observation carried forward ( LOCF ).
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 158 336 333 344
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Physical Summary Score (n=158, 336, 333, 344) -0.4495  (0.5226) 2.5498  (0.3610) 4.5726  (0.3628) 3.7964  (0.3575)
Mental Summary Score (n=158, 336, 333, 344) -0.0955  (0.5886) 2.3221  (0.4065) 2.8504  (0.4090) 4.5142  (0.4026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Physical Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Physical Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Physical Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments Mental Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments Mental Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments Mental Summary Score
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Patient's Global Assessment (PatGA) of Disease Severity
Hide Description The Patient's Global Assessment of Disease Severity is a single-item patient reported outcome measure on which participants are asked to rate by circling a number on a 0 to 5 NRS the severity of their psoriasis "today" from 0 (Clear) = no psoriasis to 5 (Severe) = the worst their psoriasis has ever been. LS mean change from baseline in patient's global assessment of disease severity score was calculated using (MMRM) with baseline score as a covariate, treatment, pooled center, visit, and treatment-by-visit interaction as fixed effects.
Time Frame Baseline, 12 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned, and had baseline and at least 1 post baseline PatGA measurement.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 164 348 339 343
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.4  (0.09) -2.1  (0.06) -3.0  (0.06) -3.2  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
16.Secondary Outcome
Title Percentage of Participants Achieving Palmoplantar PASI (PPASI) of ≥50% (PPASI50), ≥75% (PPASI75) or 100% (PPASI100) Improvement
Hide Description The Palmoplantar PASI is a composite score derived from the sum scores for erythema, induration, and desquamation multiplied by a score for the extent of palm and sole area involvement, ranging from 0 to 72. The PPASI was only assessed if participants have palmoplantar psoriasis at baseline. Participants achieving PPASI50, PPASI75 or PASI100 were defined as having an improvement of at least 50%, 75%, or of 100%, respectively, in the PPASI scores compared to baseline.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants analyzed according to the treatment to which they are assigned; and who had palmoplantar Ps involvement at baseline. Participants who did not meet clinical response criteria or have missing data will be considered non-responders.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 55 95 102 104
Measure Type: Number
Unit of Measure: percentage of participants
PPASI 50 43.6 71.6 85.3 88.5
PPASI 75 30.9 61.1 80.4 79.8
PPASI 100 25.5 50.5 69.6 71.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments PPASI 50
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments PPASI 50
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments PPASI 50
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments PPASI 75
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments PPASI 75
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments PPASI 75
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, 50 mg ETN - Induction Period
Comments PPASI 100
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q4W - Induction Period
Comments PPASI 100
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Placebo - Induction Period, Ixe Q2W - Induction Period
Comments PPASI 100
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
17.Secondary Outcome
Title Percentage of Participants With Anti-Ixekizumab Antibodies
Hide Description Percentage of participants with treatment-emergent positive anti-ixekizumab antibodies was summarized by treatment group. Percentage was calculated based on the # of evaluable participants and was calculated by number of participants with treatment-emergent positive anti-ixekizumab antibodies / number of evaluable participants * 100%.
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized participants who received at least 1 dose of study treatment and had evaluable data.
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period
Hide Arm/Group Description:
Placebo was administered as 2 subcutaneous (SC) injections every 2 weeks (Q2W) up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12.
50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10).
160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W; Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12.
Overall Number of Participants Analyzed 165 347 340 346
Measure Type: Number
Unit of Measure: percentage of participants
0 2.9 14.1 10.4
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events were summarized based on all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period Ixe/Placebo- Maintenance Period Primary Pop Ixe/Ixe Q12W - Maintenance Period Primary Pop Ixe/Ixe Q4W - Maintenance Period Primary Pop Placebo Resp/Placebo - Maintenance Period Secondary Pop Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop ETN Resp/Placebo Maintenance Period Secondary Pop ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop Ixe Q2W NonResp/Ixe Q4W Maintenance Period Secondary Pop Ixe Q4W Maintenance Period Relapsed Pop
Hide Arm/Group Description Placebo was administered as 2 subcutaneous (SC) injections Q2W up through Week 10. Placebo for ETN (1 SC injection) administered twice weekly (every 3 to 4 days) starting at Week 0 up to Week 12. 50 mg ETN was administered by 1 SC injection twice weekly (every 3-4 days) up to Week 12. Placebo for ixe was administered as 2 SC injections at Week 0 followed by Placebo for ixe administered as 1 SC injection Q2W (Weeks 2, 4, 6, 8, and 10). 160 mg ixe was administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection every 4 weeks (Q4W): (Weeks 4 and 8). Placebo was administered as 1 SC injection at Weeks 2, 6, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12. 160 mg ixe administered as 2 SC injections at Week 0 followed by 80 mg ixe as 1 SC injection Q2W at Weeks 2, 4, 6, 8, and 10. Placebo for ETN (1 SC injection) was administered twice weekly starting at Week 0 up to Week 12. Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection every 12 weeks (Q12W) up to and including Week 56. To maintain blinding with Q4W dose regimen, Placebo for ixe given as 1 SC injection at every 4 weeks from Week 16 through Week 56. Participants who received 80 mg ixe Q2W or Q4W in Induction Period (Weeks 0 to 10) and classified as responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received placebo during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received placebo in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received ETN during the Induction Period (Weeks 0 to 10) and classified as responders and were administered placebo as 2 SC injections at Week 12 followed by placebo as 1 SC injection Q4W up to and including Week 56. Participants who received ETN in Induction Period (Weeks 0 to 12) and classified as non-responders were administered 2 SC injections of placebo at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q4W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who received 80 mg ixe Q2W in Induction Period (Weeks 0 to 10) and classified as non-responders were administered 80 mg ixe as 1 SC injection and a Placebo for ixe injection at Week 12 followed by 80 mg ixe as 1 SC injection Q4W up to and including Week 56. Participants who relapsed (loss of response, sPGA ≥3 during Maintenance Period) were administered 80 mg ixe as 1 SC injection Q4W up to and including Week 56.
All-Cause Mortality
Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period Ixe/Placebo- Maintenance Period Primary Pop Ixe/Ixe Q12W - Maintenance Period Primary Pop Ixe/Ixe Q4W - Maintenance Period Primary Pop Placebo Resp/Placebo - Maintenance Period Secondary Pop Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop ETN Resp/Placebo Maintenance Period Secondary Pop ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop Ixe Q2W NonResp/Ixe Q4W Maintenance Period Secondary Pop Ixe Q4W Maintenance Period Relapsed Pop
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) 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   --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo - Induction Period 50 mg ETN - Induction Period Ixe Q4W - Induction Period Ixe Q2W - Induction Period Ixe/Placebo- Maintenance Period Primary Pop Ixe/Ixe Q12W - Maintenance Period Primary Pop Ixe/Ixe Q4W - Maintenance Period Primary Pop Placebo Resp/Placebo - Maintenance Period Secondary Pop Placebo Non-Resp/Ixe Q4W - Maintenance Period Secondary Pop ETN Resp/Placebo Maintenance Period Secondary Pop ETN NonResp/Ixe Q4W - Maintenance Period Secondary Pop Ixe Q4W Non-Resp/Ixe Q4W- Maintenance Period Secondary Pop Ixe Q2W NonResp/Ixe Q4W Maintenance Period Secondary Pop Ixe Q4W Maintenance Period Relapsed Pop
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/167 (1.20%)      8/357 (2.24%)      8/347 (2.31%)      5/350 (1.43%)      8/176 (4.55%)      14/181 (7.73%)      11/187 (5.88%)      0/3 (0.00%)      12/155 (7.74%)      2/132 (1.52%)      9/200 (4.50%)      4/75 (5.33%)      2/49 (4.08%)      14/362 (3.87%)    
Cardiac disorders                             
Angina unstable  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Atrial fibrillation  1  0/167 (0.00%)  0 0/357 (0.00%)  0 1/347 (0.29%)  1 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Coronary artery disease  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  2 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Myocardial infarction  1  0/167 (0.00%)  0 1/357 (0.28%)  1 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Pericardial effusion  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  2
Sick sinus syndrome  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 1/200 (0.50%)  1 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Eye disorders                             
Optic ischaemic neuropathy  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 1/200 (0.50%)  1 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Gastrointestinal disorders                             
Abdominal discomfort  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  1
Abdominal pain  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  2 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Abdominal pain upper  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Anal fissure  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  1 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Anal fistula  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  1 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Colitis ulcerative  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Crohn's disease  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 1/176 (0.57%)  1 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Duodenitis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 1/350 (0.29%)  1 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Gastritis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 1/350 (0.29%)  1 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Inguinal hernia  1  0/167 (0.00%)  0 0/357 (0.00%)  0 1/347 (0.29%)  1 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Oesophagitis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 1/350 (0.29%)  1 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Stomatitis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 1/75 (1.33%)  1 0/49 (0.00%)  0 0/362 (0.00%)  0
General disorders                             
Injection site reaction  1  0/167 (0.00%)  0 1/357 (0.28%)  1 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Non-cardiac chest pain  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  1 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Pyrexia  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  2
Hepatobiliary disorders                             
Bile duct obstruction  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  2 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Bile duct stone  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  2 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Cholangitis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  1 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  1
Cholecystitis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 1/132 (0.76%)  1 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Cholestasis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Hepatic mass  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 1/176 (0.57%)  1 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Immune system disorders                             
Anaphylactic reaction  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Hypersensitivity  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Infections and infestations                             
Abscess intestinal  1  0/167 (0.00%)  0 1/357 (0.28%)  1 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Abscess limb  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  1
Abscess oral  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 1/350 (0.29%)  1 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Bartholin's abscess  1  0/48 (0.00%)  0 0/122 (0.00%)  0 0/103 (0.00%)  0 0/129 (0.00%)  0 0/66 (0.00%)  0 0/61 (0.00%)  0 0/56 (0.00%)  0 0/2 (0.00%)  0 0/43 (0.00%)  0 0/43 (0.00%)  0 0/74 (0.00%)  0 0/22 (0.00%)  0 0/19 (0.00%)  0 1/129 (0.78%)  1
Bronchopneumonia  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 1/75 (1.33%)  1 0/49 (0.00%)  0 0/362 (0.00%)  0
Cellulitis  1  0/167 (0.00%)  0 1/357 (0.28%)  1 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  1 0/3 (0.00%)  0 1/155 (0.65%)  1 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 1/362 (0.28%)  1
Cellulitis staphylococcal  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 1/132 (0.76%)  1 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Cholecystitis infective  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 1/187 (0.53%)  6 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Clostridium difficile infection  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 1/176 (0.57%)  1 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Ear infection  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 1/200 (0.50%)  2 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Erysipelas  1  0/167 (0.00%)  0 0/357 (0.00%)  0 1/347 (0.29%)  1 0/350 (0.00%)  0 0/176 (0.00%)  0 0/181 (0.00%)  0 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0 0/132 (0.00%)  0 0/200 (0.00%)  0 0/75 (0.00%)  0 0/49 (0.00%)  0 0/362 (0.00%)  0
Infectious mononucleosis  1  0/167 (0.00%)  0 0/357 (0.00%)  0 0/347 (0.00%)  0 0/350 (0.00%)  0 0/176 (0.00%)  0 1/181 (0.55%)  1 0/187 (0.00%)  0 0/3 (0.00%)  0 0/155 (0.00%)  0