A Study to Evaluate the Safety and Efficacy of Rituximab in Combination With Methotrexate Compared to Methotrexate Alone in Patients With Active Rheumatoid Arthritis

NCT00299130 | Completed Phase 3 Results

• 2 other identifiers: U2973gWA17045
• Study Type: interventional
• Target: 511
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluated the efficacy and safety of rituximab in patients with active rheumatoid arthritis (RA).

Conditions

Rheumatoid Arthritis

Keywords

RA; Rituxan; SERENE

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With American College of Rheumatology (ACR) 20 Response at Week 24

  To achieve an ACR20 required at least a 20% improvement compared with Baseline in both tender joint counts (68 joints assessed for tenderness) and swollen joint counts (66 joints assessed for swelling), as well as a 20% improvement in three of the following five additional measurements: * Physician's global assessment of disease activity (assessed using a 100 mm Visual Analog Scale \[VAS\]); * Patient's global assessment of disease activity (assessed using a 100 mm VAS); * Patient's assessment of pain (assessed using a 100 mm VAS); * Health Assessment Questionnaire (HAQ; a patient completed questionnaire consisting of 20 questions, scored from 0-3); * Acute phase reactant: C-reactive protein (CRP) or, if CRP was missing, erythrocyte sedimentation rate (ESR). Participants who withdrew prematurely from the study prior to Week 24, who received rescue therapy or had insufficient data in order to calculate a clinical response were considered to be non-responders.

  Baseline and Week 24

Secondary Outcomes (29)

• Percentage of Participants With an ACR50 Response at Week 24

  Baseline and Week 24

• Percentage of Participants With an ACR70 Response at Week 24

  Baseline and Week 24

• Change From Baseline in Disease Activity Score (DAS28-ESR) at Week 24

  Baseline and Week 24

• Percentage of Participants With European League Against Rheumatism (EULAR) Response at Week 24

  Baseline and Week 24

• Percent Change From Baseline in Swollen Joint Count

  Baseline, Week 24 and Week 48

Study Arms (3)

Placebo + methotrexate (MTX)

ACTIVE COMPARATOR

Participants received placebo intravenous infusion on Days 1 and 15. From Week 16 onwards, participants could switch to receive rituximab 0.5 g (on Days 1 and 15) every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Placebo and rituximab infusions were preceded with 100 milligrams (mg) intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of MTX and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Placebo; Drug: Rituximab

Rituximab 2 x 0.5 g + MTX

EXPERIMENTAL

Participants received 0.5 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Rituximab

Rituximab 2 x 1.0 g + MTX

EXPERIMENTAL

Participants received 1.0 g rituximab administered by intravenous infusion on Days 1 and 15. After Week 24, participants received further courses of rituximab every 24 weeks for up to 5 years if they were not in clinical remission and safety criteria were met. Rituximab infusions were preceded with 100 mg intravenous methylprednisolone. Participants also received a stable dose of 10-25 mg/week of methotrexate and ≥ 5 mg/week folic acid for the duration of their participation in the study. All participants entered a 48-week safety follow-up (SFU) period following the treatment period.

Drug: Folate; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Rituximab

Interventions

Folate DRUG

A stable dose, ≥ 5 mg/week given as either a single dose or as a divided weekly dose, orally.

Placebo + methotrexate (MTX); Rituximab 2 x 0.5 g + MTX; Rituximab 2 x 1.0 g + MTX

Methotrexate DRUG

A stable dose of between 10-25 mg/week, oral or parenteral, as prescribed by the treating physician.

Placebo + methotrexate (MTX); Rituximab 2 x 0.5 g + MTX; Rituximab 2 x 1.0 g + MTX

Methylprednisolone DRUG

Intravenous infusion

Placebo + methotrexate (MTX); Rituximab 2 x 0.5 g + MTX; Rituximab 2 x 1.0 g + MTX

Placebo DRUG

Placebo to rituximab intravenous infusion

Placebo + methotrexate (MTX)

Rituximab DRUG

Intravenous infusion

Also known as: MabThera®, Rituxan®

Placebo + methotrexate (MTX); Rituximab 2 x 0.5 g + MTX; Rituximab 2 x 1.0 g + MTX

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients 18-80 years of age.
• Rheumatoid arthritis (RA) for ≥ 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of rheumatoid arthritis.
• Receiving outpatient treatment for RA.
• Swollen joint count (SJC) ≥ 8 (66 joint count), and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline.
• At screening, either
• C-reactive protein (CRP) ≥ 0.6 mg/dL (6 mg/L), or
• Erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour.
• Inadequate response to methotrexate, having received and tolerated at a dose of 10-25 mg/week it for ≥ 12 weeks.

You may not qualify if:

• Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA.
• Inflammatory joint disease other than RA, or other systemic autoimmune disorder.
• Diagnosis of juvenile rheumatoid arthritis, or RA before the age of 16.
• Surgery within 12 weeks of study or planned within 24 weeks of randomization.
• Previous treatment with any approved or investigational biological agent for RA, an anti-alpha4-integrin antibody or co-stimulation modulator, or cell-depleting therapy.

Sponsors & Collaborators

• Genentech, Inc.: lead
• Hoffmann-La Roche: collaborator

Related Publications (2)

• Emery P, Deodhar A, Rigby WF, Isaacs JD, Combe B, Racewicz AJ, Latinis K, Abud-Mendoza C, Szczepanski LJ, Roschmann RA, Chen A, Armstrong GK, Douglass W, Tyrrell H. Efficacy and safety of different doses and retreatment of rituximab: a randomised, placebo-controlled trial in patients who are biological naive with active rheumatoid arthritis and an inadequate response to methotrexate (Study Evaluating Rituximab's Efficacy in MTX iNadequate rEsponders (SERENE)). Ann Rheum Dis. 2010 Sep;69(9):1629-35. doi: 10.1136/ard.2009.119933. Epub 2010 May 20.

  PMID: 20488885 RESULT

• Lal P, Su Z, Holweg CT, Silverman GJ, Schwartzman S, Kelman A, Read S, Spaniolo G, Monroe JG, Behrens TW, Townsend MJ. Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment. Arthritis Rheum. 2011 Dec;63(12):3681-91. doi: 10.1002/art.30596.

  PMID: 22127691 DERIVED

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

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffman-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2006
• First Posted: March 6, 2006
• Study Start: October 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: July 1, 2013
• Last Updated: April 17, 2017
• Results First Posted: June 28, 2013

Record last verified: 2017-03