Clinical trial NCT00422942: A Pharmacokinetic and Pharmacodynamic Study of MabThera (Rituximab) Plus Methotrexate in Patients With Rheumatoid Arthritis (RA)
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2007-01-17
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues
timeFrame: Weeks 12, 24, and 36
measure: Change From Baseline in Absolute B Cell CD19+ Counts in Peripheral Blood
timeFrame: Weeks 4, 12, 24, 36, and 48
Secondary outcomes:
measure: Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Synovial Tissues
timeFrame: Weeks 12, 24, and 36
measure: Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Peripheral Blood
timeFrame: Weeks 4,12, 24, 36, and 48
measure: Change From Baseline in Levels of Key Cytokines (Interleukin [IL]-1beta [β], Tumor Necrosis Factor [TNF]-Alpha [α], IL-4, IL-6, IL-10, and IL-13) in Blood (Serum)
timeFrame: Days 15 and 183 and Weeks 4, 12, 24, 36, and 48
measure: Change From Baseline in Levels of Key Cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in Synovial Tissues
timeFrame: Weeks 12, 24, and 36
measure: Change From Baseline in Myelocytomatosis Oncogene (C-myc) and BCL2-associated X Protein (BAX) in Peripheral Blood
timeFrame: Days 15 and 183
measure: Percentage of Participants Achieving American College of Rheumatology 20 Percent (20%) 50%, and 70% (ACR20/50/70) Response
timeFrame: Week 48
measure: Change From Baseline in Disease Activity Score Based on 28 Joint Count (DAS28) Erythrocyte Sedimentation Rate (ESR) Score
timeFrame: Weeks 12, 24, 36, and 48
measure: Percentage of Participants Achieving Response by European League Against Rheumatism (EULAR) Category
timeFrame: Weeks 24, 36, and 48
measure: Change From Baseline in ACR Core Set
timeFrame: Week 48
measure: Change From Baseline in Modified Total Sharp Score (mTSS)
timeFrame: Weeks 24 and 48
measure: Change From Baseline in Erosion Score
timeFrame: Weeks 24 and 48
measure: Change From Baseline in Joint Space Narrowing (JSN) Score
timeFrame: Weeks 24 and 48
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: