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

NCT02065557 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: M11-2902013-003032-77
• Study Type: interventional
• Target: 101
• Locations: 13 countries
• Sites: 59

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).

Conditions

Ulcerative Colitis

Keywords

Ulcerative Colitis; adalimumab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

• Ranked Secondary Endpoint 2: Percentage of Participants With Mucosal Healing at Week 52 in Week 8 Responders Per PMS - Maintenance Period

  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

  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

  Week 52

Study Arms (6)

Adalimumab Induction Standard Dose

EXPERIMENTAL

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; Biological: Placebo

Adalimumab Induction High Dose

EXPERIMENTAL

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

Adalimumab Induction High Dose - Open Label

EXPERIMENTAL

(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

Maintenance Placebo

PLACEBO COMPARATOR

(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; Biological: Placebo

Adalimumab Maintenance Standard Dose

EXPERIMENTAL

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

Adalimumab Maintenance High Dose

EXPERIMENTAL

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

Interventions

Adalimumab BIOLOGICAL

Subcutaneous (SC) injection

Also known as: Humira

Adalimumab Induction High Dose; Adalimumab Induction High Dose - Open Label; Adalimumab Induction Standard Dose; Adalimumab Maintenance High Dose; Adalimumab Maintenance Standard Dose; Maintenance Placebo

Placebo BIOLOGICAL

Subcutaneous (SC) injection

Adalimumab Induction Standard Dose; Maintenance Placebo

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• AbbVie: lead

Study Sites (60)

Childrens Hospital LA /ID# 147452

Los Angeles, California, 90027, United States

Location

Univ California, San Francisco /ID# 120901

San Francisco, California, 94143-2204, United States

Location

Arnold Palmer Hosp Children /ID# 120898

Orlando, Florida, 32806, United States

Location

Emory University Hospital /ID# 121858

Atlanta, Georgia, 30322, United States

Location

Children's Ctr Digestive, US /ID# 121855

Atlanta, Georgia, 30342, United States

Location

University of Chicago /ID# 120904

Chicago, Illinois, 60637-1443, United States

Location

Loyola University Medical Ctr /ID# 120900

Maywood, Illinois, 60153, United States

Location

Indiana University /ID# 120908

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital /ID# 124551

Boston, Massachusetts, 02114, United States

Location

Boston Childrens Hospital /ID# 147714

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - Rochester /ID# 121056

Rochester, Minnesota, 55905-0001, United States

Location

Minnesota Gastroenterology P.A /ID# 120895

Saint Paul, Minnesota, 55114, United States

Location

Goryeb Chidlren's Hospital /ID# 121860

Morristown, New Jersey, 07960, United States

Location

North Shore University Hospital /ID# 120905

New Hyde Park, New York, 11040, United States

Location

Univ Rochester Med Ctr /ID# 127776

Rochester, New York, 14642, United States

Location

Multicare Institute for Research and Innovation /ID# 147716

Tacoma, Washington, 98405, United States

Location

Womens and Childrens Hospital /ID# 127538

Adelaide, South Australia, 5006, Australia

Location

Medizinische Universitat Wien /ID# 120802

Vienna, Vienna, 1090, Austria

Location

LKH Salzburg and Paracelsus /ID# 123457

Salzburg, 5020, Austria

Location

UZ Brussel /ID# 120798

Jette, Brussels Capital, 1090, Belgium

Location

Cliniques Universitaires Saint Luc /ID# 120797

Woluwe-Saint-Lambert, Brussels Capital, 1200, Belgium

Location

Hosp Univ Enfants Reine Fabiol /ID# 120795

Brussels, 1020, Belgium

Location

London Health Sciences Centre /ID# 127777

London, Ontario, N6A 5A5, Canada

Location

Palacky University /ID# 131388

Olomouc, 779 00, Czechia

Location

Univ Hosp, Plzen, CZ /ID# 120813

Pilsen, 305 99, Czechia

Location

Petz Aladar Megyei Oktato Korh /ID# 124323

Győr, 9023, Hungary

Location

Balassa Janos County Hospital /ID# 128474

Szekszárd, 7100, Hungary

Location

Soroka Medical Ctr /ID# 147338

Beersheba, 84101, Israel

Location

Assaf Harofeh Medical Center /ID# 147791

Be’er Ya‘aqov, 70300, Israel

Location

Rambam Health Care Campus /ID# 120827

Haifa, 3109601, Israel

Location

Shaare Zedek Medical Center /ID# 120830

Jerusalem, 91031, Israel

Location

Schneider Childrens Med Ctr /ID# 120821

Petah Tikva, 4920235, Israel

Location

Sheba Medical Center /ID# 124324

Ramat Gan, 5262100, Israel

Location

Kaplan Medical Center /ID# 150245

Rehovot, 76100, Israel

Location

Kurume University Hospital /ID# 125476

Kurume-shi, Fukuoka, 830-0011, Japan

Location

Gunma University Hospital /ID# 126345

Maebashi, Gunma, 371-8511, Japan

Location

Hokkaido P.W.F.A.C. Sapporo-Kosei General Hospital /ID# 124482

Sapporo, Hokkaido, 060-0033, Japan

Location

The Hospital of Hyogo College of Medicine /ID# 131665

Nishinomiya-shi, Hyōgo, 663-8501, Japan

Location

Saiseikai Yokohamashi Tobu /ID# 124486

Yokohama, Kanagawa, 230-0012, Japan

Location

Yokohama City Univ Medical Ctr /ID# 147763

Yokohama, Kanagawa, 232-0024, Japan

Location

Miyagi Children's Hospital /ID# 125475

Sendai, Miyagi, 989-3126, Japan

Location

Saitama Children's Medical Center /ID# 124485

Saitama-shi, Saitama, 330-8777, Japan

Location

Juntendo University Hospital /ID# 124536

Bunkyo-ku, Tokyo, 113-8431, Japan

Location

National Center for Child Health and Development /ID# 125203

Setagaya-ku, Tokyo, 157-8535, Japan

Location

Osaka General Medical Center /ID# 124535

Osaka, 558-8558, Japan

Location

Canterbury District Health Boa /ID# 120837

Christchurch, 8011, New Zealand

Location

Uni Szpital Dzieciecy w Krakowie /ID# 120915

Krakow, Lesser Poland Voivodeship, 30-663, Poland

Location

Centrum Zdrowia MDM /ID# 120910

Warsaw, Masovian Voivodeship, 00-635, Poland

Location

Gabinet Lekarski Bartosz Korcz /ID# 120916

Rzeszów, 35-210, Poland

Location

Samodzielny Publiczny Szpital /ID# 120839

Wroclaw, 50-369, Poland

Location

Polish Mothers Memorial Hosp /ID# 148497

Lodz, Łódź Voivodeship, 93-338, Poland

Location

FN s poliklinikou F.D. Rooseve /ID# 120847

Banská Bystrica, 974 09, Slovakia

Location

Univerzitna Nemocnica Bratislava /ID# 120842

Bratislava, 821 01, Slovakia

Location

Univerzitna nemocnica Martin /ID# 120844

Martin, Žilina Region, 036 01, Slovakia

Location

Hospital Univ Vall d'Hebron /ID# 120856

Barcelona, 08035, Spain

Location

Hospital Infantil Universitario Nino Jesus /ID# 121862

Madrid, 28009, Spain

Location

The Royal London Hospital /ID# 120861

London, London, City of, E1 1BB, United Kingdom

Location

The Royal Free Hospital /ID# 123142

London, London, City of, NW3 2QG, United Kingdom

Location

Royal Hosp for Sick Children /ID# 120864

Glasgow, G3 8SJ, United Kingdom

Location

Manchester Royal Infirmary, Ma /ID# 120862

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34153231 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• AbbVie Inc.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2014
• First Posted: February 19, 2014
• Study Start: October 13, 2014
• Primary Completion: February 7, 2020
• Study Completion: February 7, 2020
• Last Updated: October 5, 2020
• Results First Posted: October 5, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, 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.

Locations

CA (1); NZ (1); SL (3); AU (2); ES (2); JP (11); CZ (2); GB (4); IL (7); BE (3); HU (2); PL (5); US (16)