A Study of the Safety and Efficacy of Rituximab in Patients With Moderate to Severe Rheumatoid Arthritis Receiving Methotrexate

NCT00243412 | Completed Phase 2 Results

• 1 other identifier: U3377g
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

This was a Phase II, randomized, double-blind, multicenter study designed to evaluate the safety and efficacy of rituximab, administered at two different regimens for 2 years, in patients with moderate to severe active rheumatoid arthritis (RA) receiving stable doses of methotrexate (MTX).

Conditions

Rheumatoid Arthritis

Keywords

Rituxan; RA

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Either an Infection or a Grade III or IV Adverse Event (National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI CTCAE], Version 3.0)

  A Grade III Adverse Event (AE) is severe; defined as considerable interference with the subject's daily activities, medical intervention/therapy required and hospitalization possible. A Grade IV AE is life-threatening; defined as extreme limitation in activity, significant medical intervention/therapy required, hospitalization probable. Because of the small sample size and the small number of subjects who completed Week 104, the analysis were limited to descriptive statistics only.

  24 months

Secondary Outcomes (10)

• Change From Baseline in Disease Activity Score 28-4 C-reactive Protein (DAS28-4(CRP))

  Baseline, 24 months

• Number of Participants With American College of Rheumatology Responses (ACR20, ACR50, and ACR70)

  Baseline, 24 months

• Number of Participants With American College of Rheumatology (ACR) Major Clinical Response and/or Remission

  24 months

• Number of Participants With European League Against Rheumatism (EULAR) Response and Remission Using Disease Activity Score 28-4 (DAS28-4)C-reactive Protein (CRP)

  Baseline, 24 months

• Change From Baseline in Short Form 36 (SF 36) Summary and Subscale Scores

  Baseline, 24 Months

Study Arms (2)

Arm A: 500 mg Rituximab

EXPERIMENTAL

Rituximab: 1000 mg intravenous (IV) on Days 1 and 15 of the first cycle; 500 mg IV on Days 1 and 15 of each subsequent 6-month cycle (Months 6, 12, and 18). Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: Rituximab

Arm B: 1000 mg Rituximab

EXPERIMENTAL

Rituximab: 1000 mg IV on Days 1 and 15 of each 12-month cycle (Rituximab cycles were administered at baseline and Month 12.) For the Month 6 and 18 cycles, rituximab or placebo was administered. Corticosteroids: 100 mg IV methylprednisolone prior to each rituximab infusion For the Months 6 and 18 cycles, IV saline was administered prior to each rituximab or placebo infusion. Methotrexate: 15-25 mg/wk oral or parenteral (10-14 mg/wk if intolerant). Folate: Minimum of 1 mg/day (or folinic acid 5 mg/wk).

Drug: folate; Drug: methotrexate; Drug: methylprednisolone; Drug: Placebo; Drug: Rituximab

Interventions

folate DRUG

Minimum of 1 mg/day oral (or folinic acid 5 mg/week)

Arm A: 500 mg Rituximab; Arm B: 1000 mg Rituximab

methotrexate DRUG

15-25 mg/week oral or parenteral (10-14 mg/week if intolerant)

Arm A: 500 mg Rituximab; Arm B: 1000 mg Rituximab

methylprednisolone DRUG

100 mg intravenous (IV) prior to each rituximab infusion (For Arm B, for the Months 6 and 18 cycles, IV saline was administered prior to each placebo infusion)

Arm A: 500 mg Rituximab; Arm B: 1000 mg Rituximab

Placebo DRUG

To maintain the blind, patients in Arm B (Rituximab 1000 mg) received placebo infusions at Months 6 and 18.

Arm B: 1000 mg Rituximab

Rituximab DRUG

500 mg or 1000 mg IV\*2.

Arm A: 500 mg Rituximab; Arm B: 1000 mg Rituximab

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of RA for at least 6 months.
• Inadequate response to MTX
• Use of folate
• If female and of childbearing potential, have a negative serum pregnancy test within 8 weeks prior to first rituximab infusion

You may not qualify if:

• Diagnosis of juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) and/or RA before age 16
• Any surgical procedure, including bone/joint surgery or planned surgery within 8 weeks prior to screening or within 16 weeks of Week 1 (Day 1) visit
• Inflammatory arthritis other than RA (e.g., inflammatory bowel disease, systemic lupus erythematosus (SLE), or psoriatic arthritis)
• Functional Class IV as defined by the American College of Rheumatology (ACR) classification of functional status in RA
• Use of disease-modifying anti-rheumatic drugs (DMARDs) other than MTX within 4 weeks prior to randomization (8 weeks prior for infliximab, adalimumab, or leflunomide)
• Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer)
• Previous treatment with Tysabri\<TM\> (natalizumab)
• Previous treatment with rituximab
• Previous treatment with any cell-depleting therapies, including investigational agents
• Treatment with IV \&-globulin or Prosorba(R) Column within the previous 6 months
• Use of intra-articular or parenteral corticosteroids within 4 weeks prior to screening visit
• Receipt of a vaccine within 4 weeks prior to Day 1 infusion
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Primary or secondary immunodeficiency (history of or active)
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, renal, hepatic, endocrine, gastrointestinal, or pulmonary disease, including any pulmonary or other condition that would preclude subject participation over the ensuing 2 years

Sponsors & Collaborators

• Genentech, Inc.: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Folic Acid; Methotrexate; Methylprednisolone; Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Aminopterin; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Because of the limited sample size, interpretation of these results should be made with caution and therefore definitive conclusions cannot be made regarding differences between the two retreatment regimens studied.

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-LaRoche

800-821-8590

Study Officials

• William Reiss, Pharm.D.

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2005
• First Posted: October 24, 2005
• Study Start: August 1, 2005
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: October 7, 2011
• Results First Posted: October 7, 2011

Record last verified: 2011-09