Safety and Efficacy Study of Re-treatment With Rituximab (MabThera/Rituxan) in Patients With Active Rheumatoid Arthritis Who Respond Poorly to Anti-TNFα Therapies

Arthritis, Rheumatoid Clinical Trial

Official title:

An Open Label Study of the Efficacy and Safety of Re-treatments With Rituximab (MabThera/Rituxan) in Patients With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Anti-TNFα Therapies

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00468377
• Other study ID #: 102-21
• Status: Active, not recruiting
• Phase: Phase 3
• First received: April 30, 2007
• Last updated: November 23, 2011
• Start date: March 2004
• Est. completion date: October 2014

Study information

• Verified date: November 2011
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether repeat treatments with rituximab are safe and effective in patients with rheumatoid arthritis who no longer respond to anti-TNF therapies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 341
• Est. completion date: October 2014
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Able and willing to give written informed consent and comply with the requirements of the study protocol.

2. Patients with active rheumatoid arthritis who participated in WA17042/IDEC 102-20, have completed the Week 24 visit (in initial or rescue therapy) and continue in the post-treatment phase (wk 24-wk 104) of the study.

3. Eligible for re-treatment by the following criteria:

(i) Achieved at least 20% reduction in both SJC and TJC (at the same time) during any visit from Week 16 onwards (in either initial or rituximab rescue therapy), including visits in the post-treatment period.

(ii) Swollen joint count (SJC) = 8 (66 joint count) and tender joint count (TJC)= 8 (68 joint count).

4. 16 weeks or more has passed since the patient's last rituximab infusion.

5. Patients of reproductive potential (males and females) using a reliable means of contraception (e.g. contraceptive pill, IUD, physical barrier).

Exclusion Criteria:

Exclusion Criteria Related to RA:

1. Patients who participated in WA17042/IDEC 102-20 but withdrew into the safety follow-up at any time pre or post wk 24.

2. Previous rituximab non-responders (those patients who failed to achieve 20% reduction in both SJC and TJC at the same time during any visit from Week 16, in WA17042/IDEC 102-20 rituximab study). These patients will remain in their current study until completion or withdrawal.

Excluded Previous/Concomitant Medications:

1. Concurrent treatment with any other DMARD (apart from methotrexate), or any anti-TNF-a, anti- IL-1 or other biologic therapies.

2. Immunization with a live or attenuated vaccine (e.g. certain formulations of influenza vaccines) is specifically excluded during the study.

Exclusions for General Safety:

1. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.

2. Evidence of any new or uncontrolled concomitant disease that may permanently exclude the patient from receiving the rituximab regimen at any time such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.

3. A positive pregnancy test.

4. Intolerance or contra-indications to i.v. glucocorticosteroids.

5. Patients with known active infection of any kind (excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with i.v. anti-infectives within 4 weeks of entry into this protocol or completion of oral anti-infectives within 2 weeks prior to entry. Entry into this protocol and re-treatment may be reconsidered once the infection has fully resolved.

6. Primary or secondary immunodeficiency (history of or currently active).

7. Lack of peripheral venous access.

Laboratory Exclusion Criteria:

Patients may not enter this protocol to be re-treated until any of the following that are present have resolved.

1. Serum creatinine > 1.4 mg/dL for women or 1.6 mg/dL for men.

2. AST or ALT > 2.5 times upper limit of normal.

3. Platelet count < 100,000/µL.

4. Hemoglobin < 8.0 g/dL.

5. Neutrophils < 1.5 × 103/µL.

6. Patients who have entered the study and are found to be HBsAg negative, HBcAb positive must have a negative hepatitis B viral DNA (<29 IU/mL) and AST/ALT less than or equal to 2.5X ULN results within the last 12 weeks.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Rituximab
1 g. rituximab i.v. on Day 1 and 15

Locations

Country	Name	City	State
United States	Research Site	Greenville	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Hoffmann-La Roche	Genentech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint is the proportion of patients with an ACR20 response achieved by re-treatment at any time.		following retreatment	No
Secondary	The proportion of patients achieving an ACR50 and ACR70 response at any time following treatment.		following retreatment	No