Clinical Trial Results:
A Phase 3 Randomized, Double-blind, Placebo controlled, Parallel group Efficacy and Safety Study of SHP647 as Induction Therapy in Subjects With Moderate to Severe Crohn’s Disease (CARMEN CD 306)
Summary
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EudraCT number |
2017-000576-29 |
Trial protocol |
IE BE HU SK ES PT EE BG GR |
Global end of trial date |
18 Aug 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
03 May 2021
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First version publication date |
03 May 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SHP647-306
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03566823 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Shire
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Sponsor organisation address |
300 Shire Way, Lexington, United States, MA 02421
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Public contact |
Study Director, Shire, ClinicalTransparency@takeda.com
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Scientific contact |
Study Director, Shire, ClinicalTransparency@takeda.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Aug 2020
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Aug 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of this study was to evaluate the efficacy of ontamalimab in subjects with moderate to severe Crohn's disease (CD) in inducing clinical remission based on 2-item patient-reported outcome (PRO) (abdominal pain severity and very soft stool/liquid stool frequency) and inducing endoscopic response based on centrally read colonoscopy.
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Protection of trial subjects |
This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 (1996), the principles of the Declaration of Helsinki, as well as other applicable local ethical and legal requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Jul 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety | ||
Long term follow-up duration |
4 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bosnia and Herzegovina: 1
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Country: Number of subjects enrolled |
Colombia: 1
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Country: Number of subjects enrolled |
Japan: 1
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Mexico: 2
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Country: Number of subjects enrolled |
Ukraine: 8
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Country: Number of subjects enrolled |
United States: 5
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Country: Number of subjects enrolled |
Belgium: 2
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Slovakia: 5
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Country: Number of subjects enrolled |
Spain: 5
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Worldwide total number of subjects |
34
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EEA total number of subjects |
15
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
34
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 25 sites in the Unites States, Belgium, Bosnia and Herzegovina, Colombia, Hungary, Japan, Mexico, Slovakia, Republic of Korea, Spain and Ukraine between 17 July 2018 (first subject first visit) and 18 August 2020 (last subject last visit). | ||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 34 subjects were enrolled into the study, of which 27 subjects completed the study. Other secondary endpoints were not analyzed due to early discontinuation of the study for reasons unrelated to safety. | ||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||
Arm description |
Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Ontamalimab
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Investigational medicinal product code |
SHP647
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received placebo matched to ontamalimab SC injection, using a PFS.
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Arm title
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Ontamalimab 25 mg | ||||||||||||||||||||||||||||
Arm description |
Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Ontamalimab
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Investigational medicinal product code |
SHP647
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received 25 mg of ontamalimab SC injection, using a PFS.
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Arm title
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Ontamalimab 75 mg | ||||||||||||||||||||||||||||
Arm description |
Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Ontamalimab
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Investigational medicinal product code |
SHP647
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Other name |
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Pharmaceutical forms |
Solution for injection in pre-filled syringe
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Subjects received 75 mg of ontamalimab SC injection, using a PFS.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ontamalimab 25 mg
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Reporting group description |
Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ontamalimab 75 mg
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Reporting group description |
Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||
Reporting group title |
Ontamalimab 25 mg
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Reporting group description |
Subjects received ontamalimab 25 milligram (mg), injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||
Reporting group title |
Ontamalimab 75 mg
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Reporting group description |
Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. |
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End point title |
Number of Subjects With Clinical Remission Based on 2-item Patient-reported Outcome (PRO) at Week 16 [1] | ||||||||||||
End point description |
Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain less than or equal to (<=) 3 (based on 11 point numerical rating scale [NRS] ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency <=2 of type 6/7 (very soft stools/liquid stools) as per the Bristol Stool Form Scale (BSFS) over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Subjects with missing data at Week 16 or discontinuation before Week 16 were considered failures. Number of subjects with clinical remission were reported. The full analysis set (FAS) consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Primary
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End point timeframe |
At Week 16
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Endoscopic Response at Week 16 [2] | ||||||||||||
End point description |
Endoscopic response was defined as a decrease in Simple Endoscopic Score for Crohn’s disease (SES-CD) of at least 25 percent (%) from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of subjects with endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Primary
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End point timeframe |
At Week 16
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Remission Based on Crohn's Disease Activity Index (CDAI) Score at Week 16 | ||||||||||||
End point description |
Clinical remission was defined as a CDAI score of <150. CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Number of subjects with clinical remission as measured by CDAI were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Enhanced Endoscopic Response at Week 16 | ||||||||||||
End point description |
Enhanced endoscopic response was defined as a decrease in SES-CD by matching segments of at least 50% from baseline. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data at Week 16 or who discontinued before Week 16 were considered non-responders. Number of subjects with enhanced endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Remission Based on 2-item PRO With 4-point Scale for Abdominal Pain at Week 16 | ||||||||||||
End point description |
Clinical remission was defined by 2-item PRO subs-cores of average daily abdominal pain <=1 (based on the 4 point scale, with scores ranging from 0 [none] to 3 [severe]) over the 7 most recent days and average daily stool frequency <=3 of type 6/7 (very soft stools/liquid stools) as per the BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Subjects with missing data at Week 16 or who discontinued before Week 16 were considered failures. Number of subjects with enhanced endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Response Based on 2-item PRO With 2 Criteria at Week 16 | ||||||||||||
End point description |
Clinical response was measured by 2-item PRO; defined as meeting at least 1 of the 2 criteria: 1)A decrease of >=30%and at least 2points from baseline in the average daily worst abdominal pain over the 7most recent days, with the average daily stool frequency of type 6/7(very soft/liquid stools)either a)not worsening from baseline and/or b)average daily stool frequency <=2 of type 6/7 as per the BSFS over the 7most recent days; 2)A decrease of >=30%from baseline in average daily stool frequency of type 6/7(very soft/liquid stools)as per the BSFS over the 7most recent days, with the average daily worst abdominal pain either a)not worsening from baseline and/or b)worst daily abdominal pain <=3(based on 11-point NRS)over the 7most recent days. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with clinical response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Remission Based on 2-Item PRO With Endoscopic Response at Week 16 | ||||||||||||
End point description |
Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3(based on 11point NRS ranging from 0[no pain] to 10[worst imaginable pain])and average daily stool frequency <=2 of type 6/7(very soft stools/liquid stools)as perBSFS ranging from type1(separate hard lumps-like stools)to type7(entirely liquid stools)over the 7most recent days. Endoscopic response was defined as a decrease in SES-CDof at least 25%from baseline. SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from0-3. Scale ranges from0-56 with a higher score indicating greater severity of disease. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with clinical remission with endoscopic response were reported. The FAS consisted of all subjects in the randomized set who had received at least 1dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Complete Endoscopic Healing at Week 16 | ||||||||||||
End point description |
Clinical remission was defined by 2-item PRO subs-cores of average worst daily abdominal pain <=3(based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]) and average daily stool frequency <=2of type 6/7 (very soft stools/liquid stools)as per BSFS ranging from type1 (separate hard lumps-like stools) to type7 (entirely liquid stools) over the 7 most recent days. Endoscopic response was defined as a decrease in SES-CD of at least 25% from baseline. SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Subjects with missing data or who discontinued at/before Week16 were considered failures. Number of subjects with complete endoscopic healing were reported. The FAS consisted of all subjects in the randomized set who had received at least 1 dose of IP.
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End point type |
Secondary
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End point timeframe |
At Week 16
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Response as Measured by CDAI-100 at Week 16 | ||||||||||||
End point description |
Clinical response is measured by at least a 100-point reduction in the CDAI from baseline (CDAI-100 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
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End point type |
Secondary
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End point timeframe |
At Week 16
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Notes [3] - Data collection and analysis for this endpoint was not performed due to study termination. [4] - Data collection and analysis for this endpoint was not performed due to study termination. [5] - Data collection and analysis for this endpoint was not performed due to study termination. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Response as Measured by CDAI-70 at Week 16 | ||||||||||||
End point description |
Clinical response is measured by at least a 70-point reduction in the CDAI from baseline (CDAI-70 response). CDAI assesses CD based on clinical signs/symptoms such as number of liquid stools, intensity of abdominal pain, general well-being (subjective), and presence of complications, use of antidiarrheal, presence of abdominal mass, physical examination and hematocrit (objective). CDAI score is equal to sum of weighted scores for subjective and objective items which range from 0-149 points: asymptomatic remission, 150-220 points: mild to moderate active CD, 221-450 points: moderate to severe active CD, >451 points: severely active to fulminant disease. Higher score indicating more severity. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
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End point type |
Secondary
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End point timeframe |
At Week 16
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Notes [6] - Data collection and analysis for this endpoint was not performed due to study termination. [7] - Data collection and analysis for this endpoint was not performed due to study termination. [8] - Data collection and analysis for this endpoint was not performed due to study termination. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Clinical Remission Over Time | ||||||||||||
End point description |
Clinical remission is defined by 2-item PRO subs-cores of average worst daily abdominal pain (based on 11 point NRS ranging from 0 [no pain] to 10 [worst imaginable pain]); and average daily stool frequency of type 6/7 (very soft stools/liquid stools) as per BSFS over the 7 most recent days. BSFS ranges from 1 (separate hard lumps, hard to pass), 2 (sausage-shaped, but lumpy), 3 (like a sausage but with cracks on the surface), 4 (like a sausage or snake, smooth and soft), 5 (soft blobs with clear-cut edges), 6 (fluffy pieces with ragged edges, a mushy stool), 7 (watery, no solid pieces, entirely liquid). Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
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End point type |
Secondary
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End point timeframe |
At Week 16
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Notes [9] - Data collection and analysis for this endpoint was not performed due to study termination. [10] - Data collection and analysis for this endpoint was not performed due to study termination. [11] - Data collection and analysis for this endpoint was not performed due to study termination. |
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No statistical analyses for this end point |
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End point title |
Change From Baseline in Individual and Total Sign/Symptom Score Based on Subjects Daily Electronic Diary (e-diary) Entries | ||||||||||||
End point description |
CD clinical signs and symptoms includes total stool frequency, rectal bleeding frequency, rectal urgency frequency, nausea severity, vomiting frequency, and rectal incontinence frequency. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
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End point type |
Secondary
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End point timeframe |
Baseline and at Week 16
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Notes [12] - Data collection and analysis for this endpoint was not performed due to study termination. [13] - Data collection and analysis for this endpoint was not performed due to study termination. [14] - Data collection and analysis for this endpoint was not performed due to study termination. |
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No statistical analyses for this end point |
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End point title |
Number of Subjects With Endoscopic Healing at Week 16 | ||||||||||||
End point description |
Endoscopic healing is measured by SES-CD <=4 and at least 2-point reduction versus baseline and no sub-score >1 in any individual variable. The SES-CD considers ileum, right colon, transverse colon, left colon, rectum in terms of: size of ulcers, ulcerated surface, affected surface and presence of narrowing. Each graded from 0-3. Scale ranges from 0-56 with a higher score indicating greater severity of disease. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
At Week 16
|
||||||||||||
|
|||||||||||||
Notes [15] - Data collection and analysis for this endpoint was not performed due to study termination. [16] - Data collection and analysis for this endpoint was not performed due to study termination. [17] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) Total (Absolute) Score at Weeks 8, 12 and 16 | ||||||||||||
End point description |
The IBDQ is a psychometrically validated PRO instrument for measuring the disease-specific health-related quality of life (HRQL) in subjects with IBD, including CD. The IBDQ consists of 32 items, which are grouped into 4 domains and scored as: bowel function (10 to 70), systemic symptoms (5 to 35), emotional status (12 to 84), and social function (5 to 35). The total IBDQ score ranges from 32 to 224. For the total score and each domain, a higher score indicates better HRQL. A score of at least 170 corresponds to clinical remission and an increase of at least 16 points is considered to indicate a clinically meaningful improvement. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Weeks 8, 12 and 16
|
||||||||||||
|
|||||||||||||
Notes [18] - Data collection and analysis for this endpoint was not performed due to study termination. [19] - Data collection and analysis for this endpoint was not performed due to study termination. [20] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Change From Baseline in Short Form-36 Health Survey (SF-36) Scores at Week 16 | ||||||||||||
End point description |
The SF-36, version 2 is a generic quality-of-life instrument that has been widely used to assess HRQL of subjects. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role – physical, bodily pain, general health, vitality, social functioning, role – emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQL. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, Week 16
|
||||||||||||
|
|||||||||||||
Notes [21] - Data collection and analysis for this endpoint was not performed due to study termination. [22] - Data collection and analysis for this endpoint was not performed due to study termination. [23] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Subjects Based on Incidence of All-cause Hospitalizations | ||||||||||||
End point description |
Incidence of all cause hospitalizations was planned to be assessed. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 32
|
||||||||||||
|
|||||||||||||
Notes [24] - Data collection and analysis for this endpoint was not performed due to study termination. [25] - Data collection and analysis for this endpoint was not performed due to study termination. [26] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Subjects Based on Total Inpatient Days | ||||||||||||
End point description |
Total inpatient days were planed to be assessed. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 32
|
||||||||||||
|
|||||||||||||
Notes [27] - Data collection and analysis for this endpoint was not performed due to study termination. [28] - Data collection and analysis for this endpoint was not performed due to study termination. [29] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Number of Subjects Based on Incidence of CD-related Surgeries and Other Surgical Procedures | ||||||||||||
End point description |
Incidence of CD-related surgeries and other surgical procedures were planned to be recorded. Study terminated early for reasons unrelated to safety. Hence, for this endpoint, the planned data collection and analysis was not performed.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline up to Week 32
|
||||||||||||
|
|||||||||||||
Notes [30] - Data collection and analysis for this endpoint was not performed due to study termination. [31] - Data collection and analysis for this endpoint was not performed due to study termination. [32] - Data collection and analysis for this endpoint was not performed due to study termination. |
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
From screening up to safety follow-up period (Week 32)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.1
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Reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Subjects received ontamalimab matching-placebo, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ontamalimab 25 mg
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Reporting group description |
Subjects received ontamalimab 25 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Ontamalimab 75 mg
|
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Reporting group description |
Subjects received ontamalimab 75 mg, injection, subcutaneously using a prefilled syringe on Week 0 (Day 1), Week 4, Week 8, and Week 12 in a 16-week treatment period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
21 Aug 2018 |
Protocol Amendment 1: Updated inclusion criteria to collect additional data for abdominal pain at study entry using the 0-3 CDAI severity scale. Updated exclusion criteria to exclude subjects with non steroidal anti-inflammatory drug-induced colitis, any history of positive tuberculosis (TB) and cirrhosis with or without decompensation; to clarify that subjects with positive hepatitis B core antibody (HBcAb), without hepatitis B virus (HBV) DNA and chronic hepatitis C virus (HCV), without HCV RNA may be eligible for the study. Added new new exclusion criterion to clarify that documentation of HIV status should be performed within 6 months of screening. Added text to clarify that concomitant antidiarrheal opiate drugs were permitted if taken at stable doses for the duration of the study, with dose reduction or discontinuation allowed only if required due to clinical improvement or adverse event. Added new section to provide appropriate guidance on subjects who have been enrolled with elevated liver function test or who have elevated liver function test(s) during the study. |
||
22 Nov 2019 |
Protocol Amendment 2: Revised exclusion criterion to clarify that subjects with obstructive colonic stricture were to be excluded if it was clinically significant. Revised text to clarify the allowed doses of steroids. Added text to address FDA recommendation to evaluate the risk of hypersensitivity reactions in the Phase 3 studies and aid in the collection of relevant safety data. Updated the sample volume needed for the serum chemistry test and for the pharmacokinetic assessment. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
The study was terminated as the sponsor discontinued the ontamalimab clinical trial program in ulcerative colitis and CD for reasons unrelated to safety. |