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The Efficacy of Cobitolimod in Patients With Moderate to Severe Active Ulcerative Colitis (CONDUCT)

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: NCT03178669
Recruitment Status : Completed
First Posted : June 7, 2017
Results First Posted : February 1, 2021
Last Update Posted : February 1, 2021
Sponsor:
Information provided by (Responsible Party):
InDex Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Interventions Drug: cobitolimod
Drug: Placebo
Enrollment 213
Recruitment Details  
Pre-assignment Details 1 patient in the 2x31 mg and one patient in the 4x125 mg was never treated with study drug and excluded from analysis.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Period Title: Overall Study
Started 40 43 42 42 44
Completed Week 6 [1] 35 42 36 38 42
Completed [2] 35 42 35 38 40
Not Completed 5 1 7 4 4
Reason Not Completed
Adverse Event             4             1             4             2             2
Lack of Efficacy             0             0             2             0             1
Physician Decision             0             0             0             0             1
Withdrawal by Subject             1             0             1             1             0
Lost to Follow-up             0             0             0             1             0
[1]
Completed Week 6
[2]
Completed Week 10
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo Total
Hide Arm/Group Description

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Total of all reporting groups
Overall Number of Baseline Participants 40 43 42 42 44 211
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
47.4  (16.4) 47.0  (16.9) 46.2  (14.0) 47.2  (14.9) 45.5  (15.2) 46.6  (15.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
Female
14
  35.0%
23
  53.5%
16
  38.1%
18
  42.9%
11
  25.0%
82
  38.9%
Male
26
  65.0%
20
  46.5%
26
  61.9%
24
  57.1%
33
  75.0%
129
  61.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnicity : Asian Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
0
   0.0%
1
   2.3%
1
   2.4%
2
   4.8%
2
   4.5%
6
   2.8%
Ethnicity : White Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
39
  97.5%
42
  97.7%
40
  95.2%
39
  92.9%
42
  95.5%
202
  95.7%
Ethnicity : Other Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
1
   2.5%
0
   0.0%
1
   2.4%
1
   2.4%
0
   0.0%
3
   1.4%
Body weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
75.5  (16.70) 71.5  (14.85) 73.3  (13.15) 73.1  (17.53) 78.1  (12.89) 74.3  (15.14)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
25.1  (4.54) 24.7  (4.65) 24.5  (3.70) 24.7  (5.06) 25.9  (4.80) 25.0  (4.56)
Tobacco use at screening  
Measure Type: Count of Participants
Unit of measure:  Participants
Never smoked Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
30
  75.0%
28
  65.1%
30
  71.4%
30
  71.4%
31
  70.5%
149
  70.6%
Current smoker Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
1
   2.5%
2
   4.7%
2
   4.8%
1
   2.4%
2
   4.5%
8
   3.8%
Former smoker Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
9
  22.5%
13
  30.2%
10
  23.8%
11
  26.2%
11
  25.0%
54
  25.6%
Total inflammatory Bowel Disease Questionnaire score (IBDQ)   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
131.9  (28.11) 140.1  (32.46) 131.5  (36.64) 120.9  (34.81) 133.9  (28.58) 131.7  (32.59)
[1]
Measure Description: The IBDQ is an instrument used to assess quality of life in participants. It includes 32 questions on 4 domains : Bowel Systems (10 items), Emotional Function (12 items), Social Function (5 items), and Systemic Function (5 items). A total IBDQ score is calculated by summing the scores from each domain; the total IBDQ score ranges from 32 to 224, with lower scores reflecting worse health.
Duration of Ulcerative Colitis (UC)  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
7.88  (6.480) 8.46  (7.431) 7.89  (6.830) 8.14  (6.772) 7.36  (7.277) 7.94  (6.920)
Stool frequency per day  
Mean (Standard Deviation)
Unit of measure:  Stools per day
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
6.3  (2.93) 5.0  (1.83) 5.7  (2.73) 5.7  (2.56) 5.9  (3.04) 5.7  (2.62)
Mayo score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
8.5  (1.2) 8.0  (1.8) 8.5  (1.3) 8.3  (1.7) 8.3  (1.6) 8.3  (1.5)
[1]
Measure Description: The Mayo score is sum of 4 sub-scores (i.e., stool frequency, rectal bleeding, endoscopic findings (excluding friability at grade 1), and physician's global assessment); each rated on a scale from 0 to 3, with higher scores indicating more severe disease. The total Mayo score value ranges from 0 to 12. Higher values represent worse disease.
Mayo stool frequency subscore   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
0 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
2
   5.0%
8
  18.6%
3
   7.1%
2
   4.8%
4
   9.1%
19
   9.0%
1 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
7
  17.5%
11
  25.6%
8
  19.0%
8
  19.0%
10
  22.7%
44
  20.9%
2 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
17
  42.5%
10
  23.3%
17
  40.5%
16
  38.1%
10
  22.7%
70
  33.2%
3 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
14
  35.0%
14
  32.6%
14
  33.3%
16
  38.1%
20
  45.5%
78
  37.0%
[1]
Measure Description: Mayo stool frequency subscore: 0=normal, 1=one to two stools per day more than normal, 2=three to four stools per day more than normal, 3=more than four stools per day more than normal.
Mayo rectal bleeding subscore   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
0 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
0
   0.0%
4
   9.3%
0
   0.0%
1
   2.4%
4
   9.1%
9
   4.3%
1 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
11
  27.5%
9
  20.9%
16
  38.1%
17
  40.5%
15
  34.1%
68
  32.2%
2 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
27
  67.5%
26
  60.5%
21
  50.0%
21
  50.0%
22
  50.0%
117
  55.5%
3 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
2
   5.0%
4
   9.3%
5
  11.9%
3
   7.1%
3
   6.8%
17
   8.1%
[1]
Measure Description: Mayo rectal bleeding sub-score: 0=none, 1=visible blood with stool less than half the time, 2=visible blood with stool half the time or more, 3=passing blood alone.
Mayo endoscopic subscore   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
2 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
18
  45.0%
17
  39.5%
17
  40.5%
19
  45.2%
20
  45.5%
91
  43.1%
3 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
22
  55.0%
26
  60.5%
25
  59.5%
23
  54.8%
24
  54.5%
120
  56.9%
[1]
Measure Description: Mayo endoscopic subscore: 2=moderate disease (marked erythema, absent vascular pattern, friability, erosions), 3=severe disease (spontaneous bleeding, ulceration).
Mayo Physicians Global Assessment (PGA) subscore   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
1 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
2
   5.0%
4
   9.3%
3
   7.1%
4
   9.5%
3
   6.8%
16
   7.6%
2 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
32
  80.0%
34
  79.1%
32
  76.2%
31
  73.8%
31
  70.5%
160
  75.8%
3 Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
6
  15.0%
5
  11.6%
7
  16.7%
7
  16.7%
10
  22.7%
35
  16.6%
[1]
Measure Description: Mayo PGA subscore:1=mild disease, 2=moderate disease, 3=severe disease.
Disease extent  
Measure Type: Count of Participants
Unit of measure:  Participants
Rectosigmoid Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
23
  57.5%
22
  51.2%
19
  45.2%
23
  54.8%
21
  47.7%
108
  51.2%
Descending colon Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
17
  42.5%
21
  48.8%
23
  54.8%
19
  45.2%
23
  52.3%
103
  48.8%
Nancy Histological Index (NHI) score   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
0 Number Analyzed 40 participants 43 participants 40 participants 42 participants 44 participants 209 participants
0
   0.0%
0
   0.0%
2
   5.0%
0
   0.0%
1
   2.3%
3
   1.4%
1 Number Analyzed 40 participants 43 participants 40 participants 42 participants 44 participants 209 participants
0
   0.0%
2
   4.7%
0
   0.0%
1
   2.4%
2
   4.5%
5
   2.4%
2 Number Analyzed 40 participants 43 participants 40 participants 42 participants 44 participants 209 participants
4
  10.0%
4
   9.3%
3
   7.5%
6
  14.3%
3
   6.8%
20
   9.6%
3 Number Analyzed 40 participants 43 participants 40 participants 42 participants 44 participants 209 participants
14
  35.0%
18
  41.9%
17
  42.5%
14
  33.3%
13
  29.5%
76
  36.4%
4 Number Analyzed 40 participants 43 participants 40 participants 42 participants 44 participants 209 participants
22
  55.0%
19
  44.2%
18
  45.0%
21
  50.0%
25
  56.8%
105
  50.2%
[1]
Measure Description: Nancy Histological Index (NHI) classifies histologic status, a score from 0 to 4. Grade 0= no histological findings, grade 1= no acute acute inflammatory infiltrate, grade 2= acute inflammatory cells infiltrate and no ulceration 3= acute inflammatory cells infiltrate and no ulceration 4= ulceration. The most severe observation across all segments is used for the final NHI score. A higher score indicates more severe disease.
[2]
Measure Analysis Population Description: Missing NHI score for 2 patients
Faecal calprotectin  
Mean (Standard Deviation)
Unit of measure:  Mg/kg
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
3563  (6256) 3389  (5669) 2654  (4294) 3730  (4954) 3263  (5379) 3313  (5292)
C-reactive protein (CRP)  
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
7.6  (16.2) 4.9  (5.0) 7.1  (9.5) 9.7  (16.9) 8.1  (12.1) 7.5  (11.9)
Concomitant Ulcerative Colitis(UC) medication  
Measure Type: Count of Participants
Unit of measure:  Participants
5-aminosalicylic acid (5-ASA) Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
35
  87.5%
38
  88.4%
33
  78.6%
33
  78.6%
39
  88.6%
178
  84.4%
Corticosteroids Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
18
  45.0%
13
  30.2%
17
  40.5%
14
  33.3%
17
  38.6%
79
  37.4%
Thiopurines Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
9
  22.5%
6
  14.0%
9
  21.4%
10
  23.8%
7
  15.9%
41
  19.4%
Previous UC therapy  
Measure Type: Count of Participants
Unit of measure:  Participants
Thiopurines Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
39
  97.5%
40
  93.0%
42
 100.0%
40
  95.2%
42
  95.5%
203
  96.2%
Anti-TNF Therapy Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
9
  22.5%
10
  23.3%
9
  21.4%
12
  28.6%
8
  18.2%
48
  22.7%
Vedolizumab Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
4
  10.0%
3
   7.0%
5
  11.9%
3
   7.1%
0
   0.0%
15
   7.1%
Tofacitinib Number Analyzed 40 participants 43 participants 42 participants 42 participants 44 participants 211 participants
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.5%
1.Primary Outcome
Title Clinical Remission
Hide Description Patients with clinical remission at Week 6 (yes=1, no=0), defined by Modified Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), and iii) endoscopy score of 0 or 1 (excluding friability).
Time Frame 6 weeks after first treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Non Responder Imputation (NRI). Number of observed data is presented.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 40 43 42 42 44
Measure Type: Count of Participants
Unit of Measure: Participants
5
  12.5%
2
   4.7%
9
  21.4%
4
   9.5%
3
   6.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1806
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.0
Confidence Interval (2-Sided) 80%
0.75 to 5.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6649
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.7
Confidence Interval (2-Sided) 80%
0.20 to 2.24
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0247
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 3.8
Confidence Interval (2-Sided) 80%
1.53 to 9.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3279
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 80%
0.52 to 3.88
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Modified Clinical Remission
Hide Description Patients with modified clinical remission at Week 6 (yes=1, no=0), defined by the Modified Mayo score ≤ 2 and sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), iii) endoscopy score of 0 or 1 (excluding friability ) and iiii) physician´s global assessment (PGA) of 0 or 1
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Placebo Multiple Imputation (PMI). Number of observed data is presented in the table.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 33 41 35 39 39
Measure Type: Count of Participants
Unit of Measure: Participants
5
  15.2%
1
   2.4%
7
  20.0%
3
   7.7%
3
   7.7%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2115
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.9
Confidence Interval (2-Sided) 80%
0.69 to 4.99
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8498
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.3
Confidence Interval (2-Sided) 80%
0.06 to 1.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0977
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.6
Confidence Interval (2-Sided) 80%
1.01 to 6.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5220
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.0
Confidence Interval (2-Sided) 80%
0.32 to 2.84
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Symptomatic Remission
Hide Description Patients with symptomatic remission at Week 6 (yes=1, no=0), defined by the Mayo sub scores, i) rectal bleeding of 0, ii) stool frequency of 0 or 1 (with at least one point decrease from Baseline, Week 0), (patient reported outcome)
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Placebo Multiple Imputation (PMI). Number of observed data is presented.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 37 42 37 40 43
Measure Type: Count of Participants
Unit of Measure: Participants
10
  27.0%
11
  26.2%
13
  35.1%
10
  25.0%
9
  20.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2335
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.5
Confidence Interval (2-Sided) 80%
0.74 to 2.94
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2511
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.4
Confidence Interval (2-Sided) 80%
0.73 to 2.69
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1162
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.8
Confidence Interval (2-Sided) 80%
0.96 to 3.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3467
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.2
Confidence Interval (2-Sided) 80%
0.63 to 2.40
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Response
Hide Description Patients with clinical response at Week 6 (yes=1, no=0), defined as clinical remission or a three point and ≥30 % decrease from Baseline, Week 0 in the sum of the Modified Mayo score, i) rectal bleeding, ii) stool frequency and iii) endoscopy score (excluding friability), iiii) physicians global assessment (PGA)
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Placebo Multiple Imputation (PMI). Number of observed data is presented.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 33 41 35 39 39
Measure Type: Count of Participants
Unit of Measure: Participants
17
  51.5%
18
  43.9%
20
  57.1%
15
  38.5%
20
  51.3%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6326
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.9
Confidence Interval (2-Sided) 80%
0.50 to 1.50
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7127
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval (2-Sided) 80%
0.45 to 1.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2658
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.3
Confidence Interval (2-Sided) 80%
0.75 to 2.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8301
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6
Confidence Interval (2-Sided) 80%
0.36 to 1.16
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Endoscopic Remission
Hide Description Patients with endoscopic remission at Week 6 (yes=1, no=0), defined by the Modified Mayo endoscopic sub score of 0 or 1 (excluding friability)
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Placebo Multiple Imputation (PMI). Number of observed data is presented.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 34 41 37 39 40
Measure Type: Count of Participants
Unit of Measure: Participants
7
  20.6%
5
  12.2%
15
  40.5%
10
  25.6%
12
  30.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7994
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.6
Confidence Interval (2-Sided) 80%
0.32 to 1.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9665
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.3
Confidence Interval (2-Sided) 80%
0.16 to 0.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2049
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.5
Confidence Interval (2-Sided) 80%
0.80 to 2.82
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6504
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval (2-Sided) 80%
0.42 to 1.60
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Histological Remission
Hide Description Patients with histological remission at Week 6 (yes=1, no=0), defined by the Nancy histological index of grade 0 or 1
Time Frame Week 6
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS), was based on the intention-to-treat (ITT) principles, which consists of all randomised patients who meet the inclusion criteria (as assessed by the investigator on the inclusion/exclusion criteria form), and receive at least one dose of the study drug (active or placebo). Missing data was replaced using Placebo Multiple Imputation (PMI). Number of observed data is presented.
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description:

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

Overall Number of Participants Analyzed 35 41 37 39 41
Measure Type: Count of Participants
Unit of Measure: Participants
4
  11.4%
5
  12.2%
8
  21.6%
7
  17.9%
10
  24.4%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x31 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9207
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.4
Confidence Interval (2-Sided) 80%
0.18 to 0.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9228
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.4
Confidence Interval (2-Sided) 80%
0.19 to 0.92
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 2x250 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6636
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.8
Confidence Interval (2-Sided) 80%
0.39 to 1.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Cobitolimod Dose 4x125 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7449
Comments one-sided and adjusted for stratification factors, p values of less than 0.10 were regarded as statistically significant.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.7
Confidence Interval (2-Sided) 80%
0.34 to 1.41
Estimation Comments [Not Specified]
Time Frame Adverse Event (AE) was collected from the date of signed informed consent. During the screening period up to first treatment only AEs related to a study specific procedures should be reported. AEs were reported up to follow up visit at Week 10 (from first treatment)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Hide Arm/Group Description

Dose 31 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 250 mg of cobitolimod at 2 occasions, placebo at 2 occasions

cobitolimod: Rectal administration

Dose 125 mg of cobitolimod, at 4 occasions

cobitolimod: Rectal administration

Placebo at four occasions

Placebo: Solution manufactured to mimic cobitolimod

All-Cause Mortality
Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/40 (0.00%)      0/43 (0.00%)      0/42 (0.00%)      0/42 (0.00%)      1/44 (2.27%)    
Hide Serious Adverse Events
Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/40 (5.00%)      0/43 (0.00%)      4/42 (9.52%)      2/42 (4.76%)      2/44 (4.55%)    
Gastrointestinal disorders           
Ulcerative colitis * 1  2/40 (5.00%)  2 0/43 (0.00%)  0 3/42 (7.14%)  3 1/42 (2.38%)  1 2/44 (4.55%)  2
Abdominal hernia * 1  0/40 (0.00%)  0 0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/44 (0.00%)  0
Injury, poisoning and procedural complications           
Wound Dehiscence * 1  0/40 (0.00%)  0 0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/44 (0.00%)  0
Skin and subcutaneous tissue disorders           
Pruritus * 1  0/40 (0.00%)  0 0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/44 (0.00%)  0
Rash erythematous * 1  0/40 (0.00%)  0 0/43 (0.00%)  0 0/42 (0.00%)  0 1/42 (2.38%)  1 0/44 (0.00%)  0
Vascular disorders           
Deep vein thrombosis * 1  0/40 (0.00%)  0 0/43 (0.00%)  0 1/42 (2.38%)  1 0/42 (0.00%)  0 0/44 (0.00%)  0
1
Term from vocabulary, MedDRA (20.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cobitolimod Dose 2x31 mg Cobitolimod Dose 2x125 mg Cobitolimod Dose 2x250 mg Cobitolimod Dose 4x125 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/40 (12.50%)      12/43 (27.91%)      8/42 (19.05%)      10/42 (23.81%)      11/44 (25.00%)    
Gastrointestinal disorders           
Ulcerative colitis * 1  2/40 (5.00%)  3 5/43 (11.63%)  5 4/42 (9.52%)  5 2/42 (4.76%)  3 3/44 (6.82%)  4
General disorders           
Pyrexia * 1  1/40 (2.50%)  1 1/43 (2.33%)  1 0/42 (0.00%)  0 2/42 (4.76%)  2 3/44 (6.82%)  4
Infections and infestations           
Viral upper respiratory infection * 1  0/40 (0.00%)  0 1/43 (2.33%)  1 2/42 (4.76%)  2 2/42 (4.76%)  2 4/44 (9.09%)  4
Investigations           
Faecal calprotectin increased * 1  2/40 (5.00%)  2 0/43 (0.00%)  0 0/42 (0.00%)  2/42 (4.76%)  2 1/44 (2.27%)  1
Nervous system disorders           
Headache * 1  0/40 (0.00%)  0 5/43 (11.63%)  5 2/42 (4.76%)  2 2/42 (4.76%)  4 0/44 (0.00%)  0
1
Term from vocabulary, MedDRA (20.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Karin Arnesson, Clinical Trial Manager
Organization: InDex Pharmaceuticals
Phone: +46 8 122 038 57
EMail: karin.arnesson@indexpharma.com
Layout table for additonal information
Responsible Party: InDex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03178669    
Other Study ID Numbers: CSUC-01/16
2016-004217-26 ( EudraCT Number )
First Submitted: June 5, 2017
First Posted: June 7, 2017
Results First Submitted: November 13, 2020
Results First Posted: February 1, 2021
Last Update Posted: February 1, 2021