A Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate - Full Text View

Purpose

This is a Phase II, randomized, open-label, multicenter study designed to evaluate immune response to vaccines after administration of 1000 mg of rituximab in subjects with active RA who are receiving background MTX.

Condition	Intervention	Phase
Rheumatoid Arthritis	Drug: methotrexate Drug: methylprednisolone Drug: rituximab	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase II, Randomized, Parallel-Group, Open-Label, Multicenter Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate

Resource links provided by NLM:

MedlinePlus related topics: Rheumatoid Arthritis Tetanus

Drug Information available for: Prednisolone Prednisolone acetate Methylprednisolone acetate Methotrexate Methylprednisolone Prednisolone sodium phosphate Prednisolone phosphate Prednisolone sodium succinate Methylprednisolone sodium succinate Methotrexate sodium Rituximab

U.S. FDA Resources

Further study details as provided by Genentech:

Primary Outcome Measures:

Proportion of subjects with a positive response to tetanus toxoid adsorbed vaccine [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of subjects with a 2-fold increase in tetanus antibody titers, or with tetanus antibody titers ≥ 0.2 IU/mL [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with positive responses against an individual anti pneumococcal antibody serotype [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with positive responses against at least 50% of the serotypes (≥ 6/12) [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Levels of anti-tetanus antibody in subjects measured immediately prior to and 4 weeks after a booster vaccine [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Levels of anti pneumococcal antibody to 12 serotypes in subjects measured immediately prior to and 4 weeks after vaccination [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Levels of anti-KLH antibody in subjects measured immediately prior to the first administration of KLH and 4 weeks after the first administration of KLH [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Proportion of subjects who maintain a positive response to Candida albicans [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Proportion of subjects with an ACR 20/50/70 response [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment:	103
Study Start Date:	January 2006
Study Completion Date:	May 2012
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: methotrexate Oral or parenteral repeating dose Drug: methylprednisolone Intravenous repeating dose Drug: rituximab Intravenous repeating dose
Active Comparator: 2	Drug: methotrexate Oral or parenteral repeating dose Drug: methylprednisolone Intravenous repeating dose

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Age 18-65 years
Diagnosis of RA for at least 6 months
Receiving treatment for RA on an outpatient basis
Use of MTX at a dose of 10-25 mg/wk (oral [PO] or SC) for at least 12 weeks prior to Day 1, with the dose stable during the last 4 weeks prior to Day 1
If taking a background corticosteroid, use of the corticosteroid must be for at least 12 weeks prior to Day 1 at a stable dose during the last 4 weeks prior to Day 1
If taking one nonsteroidal anti-inflammatory drug (NSAID), use of a stable dose for at least 2 weeks prior to Day 1

Exclusion Criteria:

Rheumatic autoimmune disease other than RA or significant systemic involvement secondary to RA; Sjogren's syndrome with RA is permitted

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00282308

Sponsors and Collaborators

Genentech

Investigators

Study Director:

Ariella Kelman, M.D.

Genentech

More Information

No publications provided by Genentech

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bingham CO 3rd, Looney RJ, Deodhar A, Halsey N, Greenwald M, Codding C, Trzaskoma B, Martin F, Agarwal S, Kelman A. Immunization responses in rheumatoid arthritis patients treated with rituximab: results from a controlled clinical trial. Arthritis Rheum. 2010 Jan;62(1):64-74.

Responsible Party:	Genentech
ClinicalTrials.gov Identifier:	NCT00282308 History of Changes
Other Study ID Numbers:	U3374g
Study First Received:	January 24, 2006
Last Updated:	November 14, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Genentech:

RA
Rituxan
SIERRA

Additional relevant MeSH terms:

Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Rituximab
Methylprednisolone Hemisuccinate
Prednisolone
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone

Prednisolone hemisuccinate
Prednisolone phosphate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on June 17, 2013

A Study to Evaluate the Effects of Rituximab on Immune Responses in Subjects With Active Rheumatoid Arthritis Receiving Background Methotrexate (SIERRA)