A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00422942
First received: January 15, 2007
Last updated: October 7, 2013
Last verified: October 2013
  Purpose

This single arm study will investigate the pattern of B cell depletion in synovial tissue and peripheral blood of patients with active RA, after MabThera (1000mg iv x 2 on days 1 and 15) + methotrexate (10-25mg/week po) treatment. The clinical efficacy and pharmacokinetic profile of MabThera after treatment and retreatment will also be investigated. The anticipated time on study treatment is 2+ years, and the target sample size is <100 individuals.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: rituximab [MabThera/Rituxan]
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label, Exploratory Study of the Pharmacokinetic and Pharmacodynamic Activity of MabThera in Combination With Methotrexate in Synovial Tissue and in Peripheral Blood of Patients With Active Rheumatoid Arthritis.

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change in absolute B cell counts in synovial tissue [ Time Frame: Weeks 12, 24 and 36 ] [ Designated as safety issue: No ]
  • Change in absolute B cell counts in peripheral blood [ Time Frame: Weeks 4, 12, 24, 36 and 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change in key B cell markers and cytokines [ Time Frame: Up to week 48 ] [ Designated as safety issue: No ]
  • Percentage of patients with ACR 20/50/70 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Changes in DAS 28, EULAR response rate, ACR core set, modified Sharp score, erosion and JSN score. [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • AEs, laboratory parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: January 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: rituximab [MabThera/Rituxan]
1000mg iv on days 1 and 15
Drug: Methotrexate
10-25mg po weekly

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients 18-80 years of age;
  • RA for >=3 months;
  • receiving outpatient treatment;
  • failed treatment with >=1 DMARD (but not anti TNF or other biologic therapy);
  • inadequate response to methotrexate, having taken and tolerated it for >=12 weeks, with a stable dose for >=4 weeks.

Exclusion Criteria:

  • rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA;
  • history of, or current, inflammatory joint disease other than RA, or other systemic autoimmune disorder;
  • diagnosis of RA before the age of 16;
  • bone/joint surgery within 12 weeks of study;
  • prior use of anti-TNF or other biologic therapy, an anti-alpha 4 integrin, or any cell-depleting therapies.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00422942

Locations
Netherlands
Amsterdam, Netherlands, 1105 AZ
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00422942     History of Changes
Other Study ID Numbers: WA19078
Study First Received: January 15, 2007
Last Updated: October 7, 2013
Health Authority: Netherlands: Central Committee on Research inv. Human Subjects (CCMO)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Rituximab
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
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014