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

NCT00422942 | Terminated Phase 2 Results

• 1 other identifier: WA19078
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in Absolute B Cell Cluster Differential 19 Positive (CD19+) Counts in Synovial Tissues

  The change from baseline in absolute B cell (CD19+) counts at each visit calculated as (B cell count at visit minus B cell count at baseline) for synovial tissues.

  Weeks 12, 24, and 36

• Change From Baseline in Absolute B Cell CD19+ Counts in Peripheral Blood

  The change from baseline in absolute B cell (CD19+) count at each visit calculated as (B cell count at visit minus B cell count at baseline) for peripheral blood.

  Weeks 4, 12, 24, 36, and 48

Secondary Outcomes (12)

• Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Synovial Tissues

  Weeks 12, 24, and 36

• Change From Baseline in Absolute Counts of Cells Expressing CD20+ and CD22+ in Absolute B Cell (CD19+) Counts in Peripheral Blood

  Weeks 4,12, 24, 36, and 48

• 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)

  Days 15 and 183 and Weeks 4, 12, 24, 36, and 48

• Change From Baseline in Levels of Key Cytokines in (IL-1β, TNF-α, IL-6, and IL-10) in Synovial Tissues

  Weeks 12, 24, and 36

• Change From Baseline in Myelocytomatosis Oncogene (C-myc) and BCL2-associated X Protein (BAX) in Peripheral Blood

  Days 15 and 183

Study Arms (1)

1

EXPERIMENTAL

Drug: rituximab [MabThera/Rituxan]; Drug: Methotrexate

Interventions

rituximab [MabThera/Rituxan] DRUG

1000mg iv on days 1 and 15

1

Methotrexate DRUG

10-25mg po weekly

1

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;
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Unknown Facility

Amsterdam, 1105 AZ, Netherlands

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab; Methotrexate

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Study terminated after enrollment of 3 participants due to recruitment difficulties and since the objectives and data under study had been published from other, independent sources it was not appropriate to expose further participants to study drug.

Results Point of Contact

• Title: Medical Communications Organization
• Organization: Hoffmann-LaRoche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2007
• First Posted: January 17, 2007
• Study Start: January 1, 2006
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: July 16, 2014
• Results First Posted: July 16, 2014

Record last verified: 2014-07

Locations

NL (1)