Efficacy and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease

NCT00409682 | Completed Phase 3 Results DMC

• 2 other identifiers: M06-8062006-004814-41
• Study Type: interventional
• Target: 192
• Locations: 8 countries
• Sites: 45

Brief Summary

The purpose of this study is to determine Efficacy, Pharmacokinetics, and Safety of Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease

Conditions

Crohn's Disease

Keywords

Crohn's Disease

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 26

  Pediatric Crohn's Disease Activity Index (PCDAI) is an index used to measure disease activity of pediatric patients with Crohn's Disease assessing abdominal pain, stool frequency, patient functioning, hematocrit, erythrocyte sedimentation rate, albumin, weight, height, abdomen, perirectal disease, and extraintestinal manifestations. It ranges from 0 to 100; higher scores indicate more active disease. The primary endpoint was clinical remission as defined by PCDAI score ≤ 10. The comparison was between High-Dose adalimumab versus Low-Dose adalimumab in the intent-to-treat population.

  Week 26

Secondary Outcomes (5)

• Percent of Participants With Clinical Remission as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score ≤ 10 at Week 52

  Week 52

• Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 26

  Week 26

• Percent of Participants With Clinical Response as Defined by Pediatric Crohn's Disease Activity Index (PCDAI) Score at Week 52

  Week 52

• Change From Baseline IMPACT III Scores at Week 26 (Observed Case)

  Baseline and Week 26

• Change From Baseline IMPACT III Scores at Week 52 (Observed Case)

  Baseline and Week 52

Study Arms (3)

Open-label adalimumab (Week 0 to Week 4)

ACTIVE COMPARATOR

All subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2.

Biological: Adalimumab

Low-Dose Adalimumab: 20 mg or 10 mg eow (Week 4 to Week 52)

ACTIVE COMPARATOR

Subjects randomized to the Low-Dose treatment group received either 20 mg adalimumab every other week (eow) (if Week 4 body weight \[BW\] was greater than or equal to 40 kg) or 10 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blind (DB) ew therapy they could be switched to open-label ew therapy.

Biological: Adalimumab

High-Dose Adalimumab: 40 mg or 20 mg eow (Week 4 to Week 52)

ACTIVE COMPARATOR

Subjects randomized to the High-Dose treatment group received either 40 mg adalimumab every other week (eow) (if Week 4 body weight \[BW\] was greater than or equal to 40 kg) or 20 mg adalimumab eow (if Week 4 BW less than 40 kg). Starting at the Week 12 study visit, subjects who experienced a disease flare or were non-responders could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. If a subject continued to experience a flare or met the definition of non-response following an 8-week course of double-blinded (DB) ew therapy they could be switched to open-label ew therapy.

Biological: Adalimumab

Interventions

Adalimumab BIOLOGICAL

All subjects received an open-label adalimumab induction regimen. Subjects weighing greater than or equal to 40 kg at Baseline received 160 mg at Week 0 and 80 mg at Week 2. Subjects weighing less than 40 kg at Baseline received 80 mg at Week 0 and 40mg at Week 2.

Also known as: ABT-D2E7, adalimumab, Humira

Open-label adalimumab (Week 0 to Week 4)

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects between the ages of 6 and 17, inclusive, prior to baseline dosing.
• Subjects with a diagnosis of Crohn's disease for greater than 12 weeks prior to screening, confirmed by endoscopy or radiologic evaluation.
• PCDAI \> 30 despite concurrent treatment with an oral corticosteroid, and/or azathioprine (AZA) or 6-mercaptopurine (6-MP) or methotrexate (MTX) as defined below:
• Oral corticosteroid - Prednisone of ≥ 10 mg/day or equivalent, but not exceeding 40 mg, with a stable dose for at least two weeks prior to Baseline.
• Azathioprine or 6-MP - AZA dose of ≥ 1.5 mg/kg/day or 6-MP dose of ≥ 1 mg/kg/day rounded to the nearest available tablet formulation, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
• MTX dose of ≥ 5 mg once weekly, either subcutaneously (SC), intramuscularly (IM), or orally for subjects whose body weight is ≥ 20 kg, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
• MTX dose of 0.2 mg/kg, up to 5 mg, once weekly, either SC, IM, or orally for subjects whose body weight is \< 20 kg, or a dose that is the highest tolerated for the subject, in the opinion of the investigator (for example due to leukopenia, elevated liver enzymes, nausea, etc.) for at least 8 weeks prior to Baseline with a stable dose for at least 4 weeks prior to Baseline.
• Concurrent therapy will not be required for subjects who within the past 2 years in the opinion of the Investigator have not responded to or could not tolerate systemic corticosteroids, AZA, 6-MP, or MTX as defined below:
• Corticosteroids:
• Failed to successfully respond to corticosteroids, or
• Medical complications and/or adverse events (AEs) from corticosteroids that in the judgment of their physician, precludes their use (e.g. psychosis, uncontrolled diabetes, osteoporosis, or osteonecrosis).
• Azathioprine, 6-MP or MTX: -
• Failed to successfully respond to these drugs or
• Medical complications and/or AEs that in the judgment of their physician, precludes their use (e.g. allergic reaction, pancreatitis, elevated liver enzymes, hepatitis or leukopenia).
• If female, subjects who were sexually active and were of child-bearing potential practicing an approved method of birth control throughout the study and for 150 days after study completion. Examples of approved methods of birth control included the following:

You may not qualify if:

• History of cancer or lymphoproliferative disease other than a successfully and completely treated cutaneous squamous cell or basal cell carcinoma or carcinoma-in-situ of the cervix.
• History of listeria, histoplasmosis, chronic or active hepatitis B infection, human immunodeficiency virus (HIV), an immunodeficiency syndrome, central nervous system (CNS) demyelinating disease, or active tuberculosis (TB) (receiving treatment or not receiving treatment), severe infections such as sepsis and opportunistic infections.
• Subject with infectious colitis, ulcerative colitis or indeterminate colitis as determined by the investigator and Abbott Medical Monitor.
• Subject with symptomatic known obstructive strictures.
• Subject who had surgical bowel resections within the past 24 weeks of the Baseline visit or planned any resection at any time point while enrolled in the study.
• Subject with an ostomy or ileo-anal pouch. (Subjects with a previous ileo-rectal anastomosis were not excluded).
• Subject who had short bowel syndrome as determined by the investigator.
• Subject who was currently receiving total parenteral nutrition (TPN).
• Females who were pregnant or were currently breast-feeding.
• Subject who had received any investigational chemical agent in the past 30 days or 5 half-lives prior to Baseline (whichever was longer).
• Subject who had received any investigational biological agent in the past 16 weeks or 5 half-lives prior to Baseline (whichever was longer).
• Subject who has had systemic antibiotic, antiviral or antifungal treatment(s) within 3 weeks prior to Baseline for any non-Crohn's related infections.
• Subject with a history of clinically significant drug or alcohol abuse in the last year.
• Subjects with a poorly controlled medical condition such as: uncontrolled diabetes, recurrent infections, unstable ischemic heart disease, moderate to severe heart failure, recent cerebrovascular accidents and any other condition which, in the opinion of the investigator or the Sponsor, would put the subject at risk by participation in the protocol.
• Subjects with positive C. difficile stool assay.

Sponsors & Collaborators

• Abbott: lead

Study Sites (45)

Site Reference ID/Investigator# 10287

Los Angeles, California, 90095-1752, United States

Location

Site Reference ID/Investigator# 5223

Orange, California, 92868, United States

Location

Site Reference ID/Investigator# 4984

San Francisco, California, 94143, United States

Location

Site Reference ID/Investigator# 5222

Aurora, Colorado, 80045, United States

Location

Site Reference ID/Investigator# 5676

Hartford, Connecticut, 06106, United States

Location

Site Reference ID/Investigator# 4911

Orlando, Florida, 32801, United States

Location

Site Reference ID/Investigator# 7640

Orlando, Florida, 32806, United States

Location

Site Reference ID/Investigator# 5904

Atlanta, Georgia, 30342, United States

Location

Site Reference ID/Investigator# 4316

Chicago, Illinois, 60637, United States

Location

Site Reference ID/Investigator# 5901

Maywood, Illinois, 60153, United States

Location

Site Reference ID/Investigator# 4912

Indianapolis, Indiana, 46202, United States

Location

Site Reference ID/Investigator# 4317

Baltimore, Maryland, 21287, United States

Location

Site Reference ID/Investigator# 5102

Rochester, Minnesota, 55905, United States

Location

Site Reference ID/Investigator# 4285

Saint Paul, Minnesota, 55114, United States

Location

Site Reference ID/Investigator# 3826

Las Vegas, Nevada, 89109, United States

Location

Site Reference ID/Investigator# 6182

Morristown, New Jersey, 07962, United States

Location

Site Reference ID/Investigator# 8801

Buffalo, New York, 14222, United States

Location

Site Reference ID/Investigator# 3734

Mineola, New York, 11501, United States

Location

Site Reference ID/Investigator# 4913

New Hyde Park, New York, 11040, United States

Location

Site Reference ID/Investigator# 6257

Chapel Hill, North Carolina, 27599, United States

Location

Site Reference ID/Investigator# 4909

Cincinnati, Ohio, 45229, United States

Location

Site Reference ID/Investigator# 4914

Columbus, Ohio, 43205, United States

Location

Site Reference ID/Investigator# 5892

Philadelphia, Pennsylvania, 19104, United States

Location

Site Reference ID/Investigator# 6354

Nashville, Tennessee, 37232, United States

Location

Site Reference ID/Investigator# 4983

Seattle, Washington, 98105, United States

Location

Site Reference ID/Investigator# 4950

Milwaukee, Wisconsin, 53226, United States

Location

Site Reference ID/Investigator# 6700

Antwerp, 2020, Belgium

Location

Site Reference ID/Investigator# 7744

Brussels, 1020, Belgium

Location

Site Reference ID/Investigator# 6073

Brussels, 1200, Belgium

Location

Site Reference ID/Investigator# 5109

Calgary, T3B 6A8, Canada

Location

Site Reference ID/Investigator# 4916

Halifax, 83K 6R8, Canada

Location

Site Reference ID/Investigator# 10284

Hamilton, L8N 3Z5, Canada

Location

Site Reference ID/Investigator# 8391

London, N6A 5W9, Canada

Location

Site Reference ID/Investigator# 5169

Ottawa, K1H 8L1, Canada

Location

Site Reference ID/Investigator# 6798

Toronto, M5G 1X8, Canada

Location

Site Reference ID/Investigator# 5570

Vancouver, V6H 3V4, Canada

Location

Site Reference ID/Investigator# 6071

Prague, 15006, Czechia

Location

Site Reference ID/Investigator# 6065

Paris, 75015, France

Location

Site Reference ID/Investigator# 6072

Paris, 75019, France

Location

Site Reference ID/Investigator# 16501

Amsterdam, 1100 DD, Netherlands

Location

Site Reference ID/Investigator# 14750

Nijmegen, 6500HB, Netherlands

Location

Site Reference ID/Investigator# 13622

Rotterdam, 3015 GJ, Netherlands

Location

Site Reference ID/Investigator# 6428

Warsaw, 04-730, Poland

Location

Site Reference ID/Investigator# 6430

Wroclaw, 50-369, Poland

Location

Site Reference ID/Investigator# 7742

London, E1 1BB, United Kingdom

Location

Related Publications (3)

• Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.

  PMID: 30054164 DERIVED

• Ruemmele FM, Rosh J, Faubion WA, Dubinsky MC, Turner D, Lazar A, Eichner S, Maa JF, Alperovich G, Robinson AM, Hyams JS. Efficacy of Adalimumab for Treatment of Perianal Fistula in Children with Moderately to Severely Active Crohn's Disease: Results from IMAgINE 1 and IMAgINE 2. J Crohns Colitis. 2018 Nov 9;12(10):1249-1254. doi: 10.1093/ecco-jcc/jjy087.

  PMID: 29939254 DERIVED

• Hyams JS, Griffiths A, Markowitz J, Baldassano RN, Faubion WA Jr, Colletti RB, Dubinsky M, Kierkus J, Rosh J, Wang Y, Huang B, Bittle B, Marshall M, Lazar A. Safety and efficacy of adalimumab for moderate to severe Crohn's disease in children. Gastroenterology. 2012 Aug;143(2):365-74.e2. doi: 10.1053/j.gastro.2012.04.046. Epub 2012 May 2.

  PMID: 22562021 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Adalimumab

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System 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

Limitations and Caveats

Absence of placebo group comparative data.

Results Point of Contact

• Title: Global Medical Services
• Organization: Abbott

800-633-9110

Study Officials

• Roopal Thakkar

  Abbott

  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

Study Record Dates

• First Submitted: December 8, 2006
• First Posted: December 11, 2006
• Study Start: April 1, 2007
• Primary Completion: May 1, 2010
• Study Completion: May 1, 2010
• Last Updated: August 4, 2011
• Results First Posted: August 4, 2011

Record last verified: 2011-07

Locations

GB (1); US (26); BE (3); CA (7); PL (2); CZ (1); FR (2); NL (3)