A Study of MabThera (Rituximab) in Participants With Rheumatoid Arthritis Who Have Had an Inadequate Response to Disease-Modifying Antirheumatic Drugs (DMARD) and/or Anti-Tumor Necrosis Factor (Anti-TNF) Therapy.

NCT00503425 | Completed Phase 3 Results

• 1 other identifier: ML18606
• Study Type: interventional
• Target: 215
• Locations: 1 country
• Sites: 16

Brief Summary

This single arm study will evaluate the safety and efficacy of MabThera in participants with active rheumatoid arthritis who have had an inadequate response to prior treatment with DMARDs and/or anti-TNF alpha agent. Participants will be treated with MabThera 1000 milligrams (mg) intravenously (IV) on days 1 and 15. Participants were followed every 8 weeks to complete 24 weeks of follow-up. After completion of the Week 24 visit, the participants were followed every 3 months for up to 18 months for an overall study duration of 24 months (104 weeks). After week 36, eligible participants who achieve moderate or good response according to the European League Against Rheumatism (EULAR) response criteria will receive re-treatment with MabThera. Participants will receive concomitant treatment with DMARDs, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics throughout the study period. The anticipated time on study treatment is 2 years, and the target sample size is 200 participants.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants with non-serious AEs was exclusive of SAEs.

  Baseline up to study withdrawal or follow-up (Approximately 104 weeks)

Secondary Outcomes (4)

• Mean Change From Baseline in Disease Activity Score Based on 28 Joints (DAS 28) at Week 24

  Baseline, Week 24

• Percentage of Participants Whose DAS28 Improved by Greater Than (>) 1.2 at Week 24

  Week 24

• Percentage of Participants With EULAR DAS 28 Response at Week 24

  Week 24

• Change From Baseline in Bone Density Score at Weeks 48 and 104

  Baseline, Weeks 48 and 104 (End of treatment)

Study Arms (1)

1

EXPERIMENTAL

Drug: Rituximab [MabThera/Rituxan]

Interventions

Rituximab [MabThera/Rituxan] DRUG

1000 mg IV on days 1 and 15

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• During study entry
• Able and willing to give written informed consent and comply with the requirements of the study protocol;
• Participants with Rheumatoid Arthritis (RA) for at least 6 months, diagnosed according to the revised 1987 American College of Rheumatology (ACR) criteria for the classification of RA;
• Receiving treatment on an outpatient basis;
• Experienced an inadequate response to previous or current treatment with DMARDs because of toxicity or inadequate efficacy;
• Disease activity score (DAS28) greater than or equal to (\>=) 3.2 at screening and baseline visit.
• Age \>= 18 years;
• Participants of reproductive potential (males and females) using a reliable means of contraception (for example \[e.g.\] contraceptive pill, intrauterine device, physical barrier);
• Female participants with childbearing potential - a negative urine pregnancy test within two weeks prior to first rituximab treatment.
• During Re-Treatment
• Achieved moderate or good response according to the EULAR response criteria during any visit including visits in the post-treatment period;
• DAS28 \>=3.2;
• The participants has not been withdrawn into the safety follow-up at any time pre or post Week 24;
• weeks or more have passed since the participant's first rituximab infusion;
• No evidence of any new medical condition or laboratory test results;

You may not qualify if:

• Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (e.g., vasculitis, pulmonary fibrosis or Felty's syndrome). Sjogren's syndrome with RA was permitted;
• Functional class IV as defined by the ACR Classification of Functional Status in RA;
• History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or other systemic rheumatic disorder disorder (e.g., inflammatory bowel disease, scleroderma, inflammatory myopathy);
• Excluded Previous/Concomitant Medications
• Previous or concurrent treatment with any anti TNF-alpha therapy;
• Treatment with any investigational agent within 4 weeks of screening;
• Previous treatment with any cell depleting therapies excluding rituximab, including investigational agents;
• Immunization with a live vaccine within 4 weeks prior to the baseline visit.
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
• Significant cardiac or pulmonary disease (including obstructive pulmonary disease).
• Evidence of significant uncontrolled concomitant diseases such as cardiovascular disease, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disorders.
• Known active bacterial, viral, fungal, mycobacterial or other infection (including tuberculosis, or atypical mycobacterial disease, but excluding fungal infections of nail beds), or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening;
• History of recurrent significant infection or history of recurrent bacterial infections;
• Primary or secondary immunodeficiency (history of, or currently active);
• Active cancer, including solid tumors and hematologic malignancies (except basal cell or squamous cell carcinoma of the skin that have been excised and cured);

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (16)

Barzilai; Rheumatology

Ashkelon, 78306, Israel

Location

Assaf Harofe; Dept of Medicine B

Beer Yaakov, 6093000, Israel

Location

Soroka Medical Center; Reumatology

Beersheba, 8410101, Israel

Location

Hillel Yaffe MC; Internal C - Rheumatology

Hadera, 38100, Israel

Location

Rambam Medical Center; Rheumatology

Haifa, 3109601, Israel

Location

Bnei Zion Medical Center; Rheumatology

Haifa, 3339419, Israel

Location

Carmel Hospital; Rheumatology Dept

Haifa, 34362, Israel

Location

Wolfson Hospital; Rheumatology

Holon, 58100, Israel

Location

Hadassah Mount Scopus Hospital; Rheumatology

Jerusalem, 91240, Israel

Location

Meir Medical Center; Internal Dept A

Kfar Saba, 44281, Israel

Location

Nahariya Hospital; Rheumatology Dept

Nahariya, 22100, Israel

Location

Shaare Zedek Medical Center; Rheumatology Dept

Nahariya, 22100, Israel

Location

EMMS Nazareth; Internal Department A

Nazareth, 16100, Israel

Location

Beilinson Medical Center; Rheumatology

Petah Tikva, 4941492, Israel

Location

Kaplan Medical Center; Reumatology

Rehovot, 76100, Israel

Location

Sourasky / Ichilov Hospital; Rheumatology

Tel Aviv, 6423906, Israel

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

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

Results Point of Contact

• Title: Medical Communications
• 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 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2007
• First Posted: July 18, 2007
• Study Start: June 30, 2005
• Primary Completion: May 26, 2013
• Study Completion: May 26, 2013
• Last Updated: August 15, 2017
• Results First Posted: June 23, 2016

Record last verified: 2017-06

Locations

IL (16)