Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis

Study Overview
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Brief Summary
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The purpose of the study is to demonstrate the efficacy and safety, and to assess the pharmacokinetics of adalimumab administered subcutaneously (SC) in pediatric subjects with moderate to severe ulcerative colitis (UC).

Official Title
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A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Biological: Adalimumab
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of UC for at least 12 weeks prior to screening, confirmed by endoscopy with biopsy. Active ulcerative colitis with a Mayo Score of 6 - 12 points and endoscopy subscore of 2 - 3 despite concurrent treatment with oral corticosteroids or immunosuppressants or both. Exclusion Criteria: Subject with Crohn's disease (CD) or indeterminate colitis (IC). Current diagnosis of fulminant colitis and/or toxic megacolon. Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy. Chronic recurring infections or active tuberculosis (TB).

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adalimumab Induction Standard Dose<br>Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and matching placebo at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;Biological: Placebo<br>* Subcutaneous (SC) injection<br>|
| Experimental: Adalimumab Induction High Dose<br>Participants randomized to receive adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;|
| Experimental: Adalimumab Induction High Dose - Open Label<br>(After Amendment 4) participants assigned to open-label adalimumab 2.4 mg/kg (maximum dose of 160 mg) at Baseline and at Week 1, 1.2 mg/kg (maximum dose of 80 mg) at Week 2, followed by 0.6 mg/kg (maximum dose of 40 mg) at Week 4 and Week 6. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;|
| Placebo Comparator: Maintenance Placebo<br>(Prior to Amendment 4) participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to maintenance placebo. Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after the second flare. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;Biological: Placebo<br>* Subcutaneous (SC) injection<br>|
| Experimental: Adalimumab Maintenance Standard Dose<br>Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance standard dose (0.6 mg/kg [maximum dose of 40 mg] every other week). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after second flare. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;|
| Experimental: Adalimumab Maintenance High Dose<br>Participants demonstrating a clinical response per PMS (defined as a decrease in PMS ≥ 2 points and ≥ 30% from Baseline) at Week 8 randomized to adalimumab maintenance high dose (0.6 mg/kg [maximum dose of 40 mg] every week). Participants were to continue their blinded treatment during the maintenance period until Week 52 unless they had ≥ 2 flares and got open label rescue therapy after second flare. | Biological: Adalimumab<br>* Subcutaneous (SC) injection<br>* Other names: Humira;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Co-Primary Endpoint 1: Percentage of Participants Who Achieved Clinical Remission as Measured by Partial Mayo Score (PMS) at Week 8 - Induction Period | The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 sub scores (stool frequency, rectal bleeding and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). A negative change in PMS indicates improvement. Clinical remission was defined as a PMS ≤ 2 and no individual subscore > 1. | Week 8 | 
| Co-Primary Endpoint 2: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 52 in Week 8 Responders Per PMS - Maintenance Period | The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ranked Secondary Endpoint 1: Percentage of Participants With Clinical Response Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period | The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Clinical response per FMS is defined as a decrease in FMS ≥ 3 points and ≥ 30% from Baseline. | Week 52 | 
| Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period | The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those participants with a decrease in PMS ≥ 2 points and ≥ 30% from Baseline. Mucosal healing per Mayo endoscopy subscore is defined as a subscore of ≤ 1. | Week 52 | 
| Ranked Secondary Endpoint 3: Percentage of Participants With Clinical Remission Per FMS at Week 52 in Week 8 Remitters Per PMS - Maintenance Period | The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS remitters are defined as those participants with a PMS ≤ 2 and no individual subscore > 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1. | Week 52 | 
| Ranked Secondary Endpoint 4: Percentage of Participants With Corticosteroid-Free Clinical Remission Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period | The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). The PMS (Mayo score without endoscopy) ranges from 0 (normal or inactive disease) to 9 (severe disease) and is calculated as the sum of 3 subscores (stool frequency, rectal bleeding and physician's global assessment). Negative changes indicate improvement. PMS responders are defined as those with a decrease in PMS ≥ 2 points and ≥ 30% from baseline. Among participants receiving systemic corticosteroids at Baseline, corticosteroid-free clinical remission per FMS at Week 52 is defined as having discontinued systemic corticosteroids prior to Week 52 and being in FMS clinical remission at Week 52 (defined as Mayo Score ≤ 2 and no individual subscore > 1). | Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ulcerative Colitis, adalimumab