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

Phase 3

Completed

Conditions: Ulcerative Colitis

Interventions: Biological: Adalimumab
Biological: Placebo

Registration Number: NCT02065557

Lead Sponsor: AbbVie

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 101

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Adalimumab Induction Standard Dose	Adalimumab	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.
Maintenance Placebo	Adalimumab	(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.
Adalimumab Induction Standard Dose	Placebo	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.
Adalimumab Induction High Dose	Adalimumab	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.
Adalimumab Induction High Dose - Open Label	Adalimumab	(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.
Adalimumab Maintenance High Dose	Adalimumab	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.
Maintenance Placebo	Placebo	(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.
Adalimumab Maintenance Standard Dose	Adalimumab	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.

Primary Outcome Measures

Name	Time	Method
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	Week 52	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.
Co-Primary Endpoint 1: Percentage of Participants Who Achieved Clinical Remission as Measured by Partial Mayo Score (PMS) at Week 8 - Induction Period	Week 8	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.

Secondary Outcome Measures

Name	Time	Method
Ranked Secondary Endpoint 1: Percentage of Participants With Clinical Response Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period	Week 52	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.
Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period	Week 52	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.
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	Week 52	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).
Ranked Secondary Endpoint 3: Percentage of Participants With Clinical Remission Per FMS at Week 52 in Week 8 Remitters Per PMS - Maintenance Period	Week 52	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.

Trial Locations

Locations (60): Womens and Childrens Hospital /ID# 127538
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Adelaide, South Australia, Australia
Children's Ctr Digestive, US /ID# 121855
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Atlanta, Georgia, United States
University of Chicago /ID# 120904
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Chicago, Illinois, United States
Gunma University Hospital /ID# 126345
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Maebashi-shi, Gunma, Japan
FN s poliklinikou F.D. Rooseve /ID# 120847
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Banska Bystrica, Slovakia
Massachusetts General Hospital /ID# 124551
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Boston, Massachusetts, United States
Univ Rochester Med Ctr /ID# 127776
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Rochester, New York, United States
Multicare Institute for Research and Innovation /ID# 147716
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Tacoma, Washington, United States
Loyola University Medical Ctr /ID# 120900
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Maywood, Illinois, United States
Indiana University /ID# 120908
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Indianapolis, Indiana, United States
Minnesota Gastroenterology P.A /ID# 120895
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Saint Paul, Minnesota, United States
Balassa Janos County Hospital /ID# 128474
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Szekszard, Hungary
Kurume University Hospital /ID# 125476
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Kurume-shi, Fukuoka, Japan
The Hospital of Hyogo College of Medicine /ID# 131665
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Nishinomiya-shi, Hyogo, Japan
Boston Childrens Hospital /ID# 147714
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Boston, Massachusetts, United States
UZ Brussel /ID# 120798
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Jette, Bruxelles-Capitale, Belgium
Cliniques Universitaires Saint Luc /ID# 120797
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Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Yokohama City Univ Medical Ctr /ID# 147763
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Yokohama, Kanagawa, Japan
Saitama Children's Medical Center /ID# 124485
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Saitama-shi, Saitama, Japan
Juntendo University Hospital /ID# 124536
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Bunkyo-ku, Tokyo, Japan
London Health Sciences Centre /ID# 127777
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London, Ontario, Canada
Medizinische Universitat Wien /ID# 120802
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Vienna, Wien, Austria
LKH Salzburg and Paracelsus /ID# 123457
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Salzburg, Austria
Hosp Univ Enfants Reine Fabiol /ID# 120795
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Brussels, Belgium
Assaf Harofeh Medical Center /ID# 147791
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Be'er Ya'akov, Israel
Centrum Zdrowia MDM /ID# 120910
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Warsaw, Mazowieckie, Poland
Univerzitna Nemocnica Bratislava /ID# 120842
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Bratislava, Slovakia
Schneider Childrens Med Ctr /ID# 120821
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Petah Tikva, Israel
Kaplan Medical Center /ID# 150245
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Rehovot, Israel
Miyagi Children's Hospital /ID# 125475
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Sendai-shi, Miyagi, Japan
Osaka General Medical Center /ID# 124535
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Osaka, Japan
Polish Mothers Memorial Hosp /ID# 148497
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Lodz, Lodzkie, Poland
Gabinet Lekarski Bartosz Korcz /ID# 120916
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Rzeszow, Poland
Univerzitna nemocnica Martin /ID# 120844
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Martin, Zilinsky Kraj, Slovakia
Univ California, San Francisco /ID# 120901
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San Francisco, California, United States
Mayo Clinic - Rochester /ID# 121056
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Rochester, Minnesota, United States
Childrens Hospital LA /ID# 147452
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Los Angeles, California, United States
Arnold Palmer Hosp Children /ID# 120898
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Orlando, Florida, United States
Emory University Hospital /ID# 121858
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Atlanta, Georgia, United States
Goryeb Chidlren's Hospital /ID# 121860
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Morristown, New Jersey, United States
Palacky University /ID# 131388
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Olomouc, Czechia
Petz Aladar Megyei Oktato Korh /ID# 124323
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Gyor, Hungary
Soroka Medical Ctr /ID# 147338
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Be'er Sheva, Israel
Rambam Health Care Campus /ID# 120827
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Haifa, Israel
Shaare Zedek Medical Center /ID# 120830
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Jerusalem, Israel
Sheba Medical Center /ID# 124324
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Ramat Gan, Israel
Univ Hosp, Plzen, CZ /ID# 120813
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Plzen, Czechia
Saiseikai Yokohamashi Tobu /ID# 124486
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Yokohama-shi, Kanagawa, Japan
Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 124482
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Sapporo-shi, Hokkaido, Japan
Canterbury District Health Boa /ID# 120837
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Christchurch, New Zealand
Uni Szpital Dzieciecy w Krakowie /ID# 120915
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Cracow, Malopolskie, Poland
Samodzielny Publiczny Szpital /ID# 120839
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Wroclaw, Poland
Hospital Infantil Universitario Nino Jesus /ID# 121862
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Madrid, Spain
The Royal Free Hospital /ID# 123142
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London, London, City Of, United Kingdom
Hospital Univ Vall d'Hebron /ID# 120856
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Barcelona, Spain
The Royal London Hospital /ID# 120861
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London, London, City Of, United Kingdom
Royal Hosp for Sick Children /ID# 120864
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Glasgow, United Kingdom
Manchester Royal Infirmary, Ma /ID# 120862
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Manchester, United Kingdom
North Shore University Hospital /ID# 120905
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New Hyde Park, New York, United States
National Center for Child Health and Development /ID# 125203
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Setagaya-ku, Tokyo, Japan