Trial information
A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA)
Status: No longer recruiting
Protocol number: WA19078
Sponsor: Hoffmann-La Roche
Company division: Pharmaceutical
Official Scientific 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.
Brief summary: 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. Target sample size is 30.
Study phase: II
Study type: Interventional; Treatment; Non-Randomized; Open Label; Uncontrolled; Single Group; Pharmacokinetics/dynamics study
Condition: Rheumatoid Arthritis
Intervention type: Drug
Intervention name: rituximab [Mabthera/Rituxan]
Primary outcome: 1. Change in absolute B cell counts in synovial tissue Time frame: Weeks 12, 24 and 36
2. Change in absolute B cell counts in peripheral blood Time frame: Weeks 4, 12, 24, 36 and 48
Key secondary outcomes: 1. Change in key B cell markers and cytokines Time frame: Up to week 48
2. Percentage of patients with ACR 20/50/70 Time frame: Week 48
3. Changes in DAS 28, EULAR response rate, ACR core set, modified Sharp score, erosion and JSN score. Time frame: Week 48
4. AEs, laboratory parameters Time frame: Throughout study
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.
Gender: Males or Females
Age limits: Min: 18 Years Max: 80 Years
Accepts healthy volunteers: No
Anticipated start date: January, 2006
Trial registration date: 03/10/2006
Date last updated: 8/19/2008
Link to trial result
This trial was conducted at the following locations:
Netherlands
