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

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ClinicalTrials.gov Identifier: NCT02065557
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : October 5, 2020
Last Update Posted : October 5, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Tracking Information
First Submitted Date  ICMJE February 17, 2014
First Posted Date  ICMJE February 19, 2014
Results First Submitted Date  ICMJE September 10, 2020
Results First Posted Date  ICMJE October 5, 2020
Last Update Posted Date October 5, 2020
Actual Study Start Date  ICMJE October 13, 2014
Actual Primary Completion Date February 7, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 10, 2020)
  • Co-Primary Endpoint 1: Percentage of Participants Who Achieved Clinical Remission as Measured by Partial Mayo Score (PMS) at Week 8 - Induction Period [ Time Frame: 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.
  • 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 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • Proportion of subjects who achieve clinical remission [ Time Frame: Week 8 ]
    Measured by Partial Mayo Score (PMS)
  • Proportion of subjects who responded at Week 8 per PMS and achieve clinical remission [ Time Frame: Week 52 ]
    Measured by Mayo score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 10, 2020)
  • Ranked Secondary Endpoint 1: Percentage of Participants With Clinical Response Per FMS at Week 52 in Week 8 Responders Per PMS - Maintenance Period [ Time Frame: 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 [ Time Frame: 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 3: Percentage of Participants With Clinical Remission Per FMS at Week 52 in Week 8 Remitters Per PMS - Maintenance Period [ Time Frame: 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.
  • 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 [ Time Frame: 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).
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2014)
  • Proportion of subjects who achieve mucosal healing [ Time Frame: Week 52 ]
    Measured by Mayo endoscopy subscore (defined as ≤ 1) in Week 8 responders per PMS
  • Proportion of subjects in Pediatric Ulcerative Colitis Activity Index (PUCAI) remission [ Time Frame: Week 52 ]
    Measured by PUCAI remission (defined as < 10) in Week 8 responders per PMS
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis
Official Title  ICMJE A Multicenter, Randomized, Double-Blind Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Ulcerative Colitis
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Ulcerative Colitis
Intervention  ICMJE
  • Biological: Adalimumab
    Subcutaneous (SC) injection
    Other Name: Humira
  • Biological: Placebo
    Subcutaneous (SC) injection
Study Arms  ICMJE
  • Experimental: Adalimumab Induction Standard Dose
    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.
    Interventions:
    • Biological: Adalimumab
    • Biological: Placebo
  • Experimental: Adalimumab Induction High Dose
    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.
    Intervention: Biological: Adalimumab
  • Experimental: Adalimumab Induction High Dose - Open Label
    (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.
    Intervention: Biological: Adalimumab
  • Placebo Comparator: Maintenance 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.
    Interventions:
    • Biological: Adalimumab
    • Biological: Placebo
  • Experimental: Adalimumab Maintenance Standard Dose
    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.
    Intervention: Biological: Adalimumab
  • Experimental: Adalimumab Maintenance High Dose
    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.
    Intervention: Biological: Adalimumab
Publications * Croft NM, Faubion WA Jr, Kugathasan S, Kierkus J, Ruemmele FM, Shimizu T, Mostafa NM, Venetucci M, Finney-Hayward T, Sanchez Gonzalez Y, Bereswill M, Lazar A, Turner D. Efficacy and safety of adalimumab in paediatric patients with moderate-to-severe ulcerative colitis (ENVISION I): a randomised, controlled, phase 3 study. Lancet Gastroenterol Hepatol. 2021 Aug;6(8):616-627. doi: 10.1016/S2468-1253(21)00142-4. Epub 2021 Jun 19.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 14, 2020)
101
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2014)
225
Actual Study Completion Date  ICMJE February 7, 2020
Actual Primary Completion Date February 7, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Austria,   Belgium,   Canada,   Czechia,   Hungary,   Israel,   Japan,   New Zealand,   Poland,   Slovakia,   Spain,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Italy,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT02065557
Other Study ID Numbers  ICMJE M11-290
2013-003032-77 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html
Responsible Party AbbVie
Study Sponsor  ICMJE AbbVie
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: AbbVie Inc. AbbVie
PRS Account AbbVie
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP