NCT00298272

Safety and Tolerability of Rituxan With Methotrexate and Etanercept or Methotrexate and Adalimumab in Patients With Active Rheumatoid Arthritis

A Randomized, Double-Blinded, Placebo Controlled Study to Evaluate the Tolerability and Safety of Rituximab When Given in Combination With Methotrexate and Etanercept (Enbrel) or Methotrexate and Adalimumab (Humira) in Subjects With Active Rheumatoid Arthritis

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (actual)
• Sponsor: Biogen · Industry
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The primary objective of this study was to evaluate the tolerability and safety of rituximab in combination with methotrexate (MTX) and etanercept or adalimumab in participants with active rheumatoid arthritis (RA). The secondary objective was to explore the efficacy of rituximab in combination with MTX and etanercept or adalimumab in participants with active RA.

Detailed description

The study consists of 4 parts: screening, treatment, post-treatment, and safety follow-up. Prior to Day 1, participants were discontinued from all disease-modifying anti-rheumatic drugs (DMARDs) except MTX and etanercept or adalimumab. All participants who met eligibility criteria and were enrolled in the trial were randomized to receive 500 mg rituximab or placebo on Day 1 and Day 15. A subset of 18 participants was enrolled initially and followed through Week 12 for safety. The remaining 42 participants were to be enrolled after the last participant in the subset completed Week 12 and the Data Safety Monitoring Board (DSMB) conducted a safety review and approved enrollment of these additional participants. Participants were dosed on Day 1 and Day 15 and followed for 56 weeks, while remaining on their current dose of MTX and etanercept or adalimumab throughout the study. The primary endpoint was assessed at Week 24. All participants in double-blind treatment, including those who received placebo or rituximab, who met the open label inclusion/exclusion criteria anytime from Week 24 through Week 40, were eligible to enter the open label retreatment phase. These participants received open label rituximab on Day 1 and Day 15 of the retreatment phase, and were followed monthly until Week 24 then every 2 months until Week 56, while remaining on their current dose of MTX and etanercept or adalimumab throughout the study. Participants received 1 course of open label treatment only. All participants were required to return for safety follow-up (SFU) assessments at Weeks 4, 12, 24, 36, and 48 after withdrawal or completion of the study. Participants whose peripheral CD20+ B cells remained depleted at the end of the SFU periods for the primary and OL portions of the study entered extended safety follow-up (ESFU). Assessments for ESFU were performed at 12-week intervals until peripheral B-cell levels returned to within normal range or baseline level (whichever was lower).

Conditions

• Rheumatoid Arthritis

Interventions

Type	Name	Description
BIOLOGICAL	IDEC-C2B8 (rituximab)	Participants will receive 500 mg rituximab on Day 1 and Day 15
DRUG	Placebo	Participants will receive placebo on Day 1 and Day 15
DRUG	Methotrexate	Participants must have been treated with MTX ≥15 mg per week and ≤25 mg per week (dose may have been as low as 10 mg if unable to tolerate higher dose) for at least 12 weeks immediately prior to Day 1, at a stable dose for at least 4 weeks and was continued for the study duration.
DRUG	Etanercept	Participants must have been treated with etanercept at 50 mg per week (25 mg twice per week or 50 mg once per week).
DRUG	Adalimumab	Participants must have been treated with adalimumab at 40 mg every other week for at least 12 weeks immediately prior to Day 1.
DRUG	Methylprednisolone	Methylprednisolone 100 mg IV was administered by slow infusion to be completed at least 30 minutes prior to each infusion of rituximab or placebo.
DIETARY_SUPPLEMENT	Folate	All subjects also received a stable dose of folate (≥5 mg per week).

Timeline

• Start date: 2006-05-01
• Primary completion: 2009-04-01
• Completion: 2011-07-01
• First posted: 2006-03-02
• Last updated: 2015-09-28
• Results posted: 2010-11-17

Locations

18 sites across 1 country: United States