NCT00409682

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

A Multi-Center, Double-Blind Study to Evaluate the Safety, Efficacy and Pharmacokinetics of the Human Anti-TNF Monoclonal Antibody Adalimumab in Pediatric Subjects With Moderate to Severe Crohn's Disease

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 192 (actual)
• Sponsor: Abbott · Industry
• Sex: All
• Age: 6 Years – 17 Years
• Healthy volunteers: Not accepted

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

Detailed description

M06-806 (NCT # NCT00409682) was a Phase 3, multi-center, randomized, double-blind (DB), efficacy, safety, and pharmacokinetic (PK) study designed to evaluate the efficacy of 2 dose regimens for the induction and maintenance of clinical remission in pediatric subjects between the ages of 6 and 17 (inclusive) with moderate to severe Crohn's disease (CD) (defined by Pediatric Crohn's Disease Activity Index \[PCDAI \> 30\]). Subjects must have either failed conventional therapy for CD or have previously received infliximab and lost response/had intolerance to infliximab. Approximately 186 pediatric subjects between the ages of 6 and 17 were planned to be entered into the study at approximately 55 sites in the US, Canada, and Europe. At least 80 subjects were to be ≥ 13 years old at Baseline and one-third to one-half of the study population were to be subjects who had previously lost response or were intolerant to infliximab. The duration of the study was to be up to 65 weeks, which included a 1- to 3-week Screening period, an Induction period, a Maintenance period, and a 70-day follow-up phone call for all subjects that either terminated early from the study or did not rollover into the extension study (\[NCT # 00686374\], to evaluate the long-term maintenance of clinical response, safety, and tolerability of repeated administration of adalimumab). All subjects received an induction regimen administered at Baseline (Week 0) and Week 2. The open-label (OL) induction dose was based on the subject's Baseline body weight. Subjects weighing ≥ 40 kg were to receive 160 mg at Week 0 and 80 mg adalimumab at Week 2. Subjects weighing \< 40 kg were to receive 80 mg at Week 0 and 40 mg adalimumab at Week 2. At Week 4, subjects were to be randomized 1:1 to 1 of 2 DB maintenance treatment groups (Low-Dose or High-Dose), stratified by Week 4 clinical responder status (clinical response was defined as decrease in PCDAI of ≥ 15 points from the Baseline score), body weight at Week 4 and prior exposure to infliximab. Subjects randomized to the High-Dose treatment group were to receive either 40 mg adalimumab subcutaneous (SC) every other week (eow) (if Week 4 body weight ≥ 40 kg) or 20 mg adalimumab SC eow (if Week 4 body weight \< 40 kg). Subjects randomized to the Low-Dose treatment group were to receive either 20 mg adalimumab SC eow (if Week 4 body weight ≥ 40 kg) or 10 mg adalimumab SC eow (if Week 4 body weight \< 40 kg). Subject's body weight taken at Week 26 was to be used to readjust the maintenance dosing regimen for a subject whose body weight had increased from \< 40 kg to ≥ 40 kg during the study. Subjects were expected to remain on blinded eow therapy throughout the 48-week study DB Maintenance period. However, starting at the Week 12 study visit, subjects who experienced a disease flare (increase in the PCDAI ≥ 15 points when compared to Week 4 and an absolute PCDAI above 30) or were non-responders (not achieving a decrease in the PCDAI score of at least 15 points when compared to the Baseline score for 2 consecutive visits at least 2 weeks apart) could be switched from blinded eow dosing to blinded every week (ew) dosing, continuing with the same blinded dose. During blinded ew treatment, if a subject continued to experience a flare or met the definition of non-response following an 8 week course of DB ew therapy, they were to be switched to OL ew therapy. The dosage of the OL ew therapy was 20 mg for subjects \< 40 kg and 40 mg for subjects ≥ 40 kg. This study used the PCDAI to determine efficacy of the study drug. The primary efficacy endpoint is the proportion of subjects who are in clinical remission at Week 26, as measured by the PCDAI in the intent-to-treat population. Clinical remission is defined as a PCDAI score of ≤ 10. The clinical response indicators include clinical remission as defined by PCDAI score at Week 52 and clinical response as defined by PCDAI score at Week 26 and at Week 52. The patient reported outcome is the change from Baseline in total IMPACT III scores at Week 26 and Week 52. The safety parameters (adverse events, laboratory data, and vital signs) were assessed at all visits throughout the study.

Conditions

• Crohn's Disease

Interventions

Type	Name	Description
BIOLOGICAL	Adalimumab	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	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	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.

Timeline

• Start date: 2007-04-01
• Primary completion: 2010-05-01
• Completion: 2010-05-01
• First posted: 2006-12-11
• Last updated: 2011-08-04
• Results posted: 2011-08-04

Locations

45 sites across 8 countries: United States, Belgium, Canada, Czechia, France, Netherlands, Poland, United Kingdom