Rituximab for the Treatment of Early Rheumatoid Arthritis (RA)

NCT00396812 | Terminated Phase 1 Results

• 1 other identifier: DAIT ARA04
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint swelling, pain, stiffness, damage, and ultimately loss of joint function. Scientists estimate that about 1.3 million people (0.6 percent) of the U.S. adult population have RA. Current therapies target the immune system early in the disease process before joint damage occurs, and include drugs such as methotrexate (MTX) and tumor necrosis factor (TNF)-blocking agents. Rituximab is a disease-modifying antirheumatic drug (DMARD) recently approved by the FDA for use in combination with MTX for treatment of moderately to severely active RA in patients who have had an inadequate response to TNF-blocking agents, in an effort to try to slow the course of the disease. This study will examine the effects of rituximab on the immune response and disease activity in participants with early RA who have not been treated with any disease-modifying agent. In addition, the safety and tolerability of rituximab in this population will be examined.

Conditions

Rheumatoid Arthritis

Keywords

Autoimmune disease; Biologic response modifiers; Disease-modifying antirheumatic drugs (DMARDS); Immune system; Rheumatoid arthritis (RA); Rituximab (anti-CD20 monoclonal antibodies)

Outcome Measures

Primary Outcomes (9)

• Change From Baseline in the Disease Activity Score- Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 48

  The DAS28-ESR is a score on a scale (0 to 10) that is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR (mm/hour). Lower score indicates less disease activity. Flares in disease activity are defined as an increase in this score of greater than 1.2 and remission is defined as achieving a DAS28-ESR score of less than 2.6.

  Baseline (Day 0), Week 48

• Change From Baseline in Tender Joint Count Score at Week 48

  Tender Joint Count (TJC) is calculated based on tenderness response of 28 joints. TJC possible values range from 0 to 28. A lower TJC indicates less joint tenderness. Change from baseline is computed as Week 48 value minus baseline value. A negative value in change from baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in Swollen Joint Count at Week 48

  Swollen Joint Count (SJC) is calculated based on swelling response of 28 joints. SJC possible values range from 0 to 28. A lower SJC indicates less joint swelling. Change from baseline is computed as Week 48 value minus baseline value. A negative value in change from baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in Patient's Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 48

  Change from Baseline in PAAP-VAS (0 to 100 millimeters visual analog scale, 0 being no pain and 100 being most severe pain) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in Patient's Global Assessment of Disease Activity- Visual Analog Scale (PtGADA-VAS) at Week 48

  Change from Baseline in PtGADA-VAS (0 to 100 millimeters visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in Physician's Global Assessment of Patient's Disease Activity- Visual Analog Scale (PhGADA-VAS) at Week 48

  Change from Baseline in PhGADA-VAS (0 to 100 millimeters visual analog scale, 0 being no symptoms and 100 being severe symptoms) is computed as the value at Week 48 minus the Baseline value. A negative value in change from Baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in the Short Form 36 (SF-36) Physical and Mental Health Component Summary Scores (PCS and MCS) at Week 48

  SF-36 measures health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores: PCS=physical functioning, role-physical, bodily pain, and general health; MCS=vitality, social functioning, role-emotional, and mental health. Scoring is done for both subscores and summary scores. For both, 0=worst score (or quality of life) and 100=best score. Change from baseline is computed as the value at Week 48 minus the baseline value. A positive value in change from Baseline indicates an improvement and a negative value worsening.

  Baseline (Day 0), Week 48

• Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 48

  HAQ-DI is derived based on the mean of individual scores in 8 categories of daily living activities (using 20 questions). Each question is scored 0-3 (0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty, and 3 = unable to do). In addition, category scores are modified if an aid or device is used, for example, a walker or wheelchair, or help is received from another person in the daily living activities. If an aid or device is used or help is received then a category score of 0 or 1 increases to a category score of 2. A category score of 3 remains a 3 regardless of aids, devices, or help. Scores from each of the 8 categories are totaled. The total score can range from 0 to 24. Change from baseline is computed as the total score at Week 48 minus the baseline total score. A negative value in change from baseline indicates an improvement.

  Baseline (Day 0), Week 48

• Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 48

  ESR is a blood test used to monitor therapy in inflammatory diseases such as rheumatoid arthritis and reflects acute phase reactant levels. Active disease in RA is defined by an ESR greater than 30 mm/hr. Change from baseline is computed as the value at Week 48 minus the baseline value. A negative value in change from baseline indicates an improvement.

  Baseline (Day 0), Week 48

Study Arms (1)

Rituximab

EXPERIMENTAL

Drug: Rituximab

Interventions

Rituximab DRUG

Participants to receive an intravenous infusion of rituximab (1 gram ) fourteen days apart, at baseline (Day 0) and at Week 2. Concomitant treatments to be administered at a dose and frequency prescribed per protocol include methotrexate (MTX) and folic or folinic acid.

Also known as: Anti-CD20 antibody therapy, Rituxan

Rituximab

Eligibility Criteria

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

You may qualify if:

• Diagnosis of RA, as defined by fulfilling at least four of seven American College of Rheumatology (ACR) criteria
• Positive for rheumatoid factor (RF) and/or anticyclic citrullinated peptide (CCP)
• The presence of arthritis symptoms for more than 6 weeks but less than 1 year
• Active RA, as defined by at least four swollen joints, at least four tender joints, and either an erythrocyte sedimentation rate (ESR) of greater than 30 mm/hr OR C-reactive protein level greater than 1.0 mg/dL (normal less than 0.4)
• Willing to adhere to the study requirements
• Willing to use acceptable effective forms of contraception

You may not qualify if:

• Allergy to methotrexate (MTX)
• Previous exposure to anti-CD20 monoclonal antibody (mAb) or other type(s) of mAb therapy
• Previous disease-modifying anti-rheumatic drugs (DMARD) therapy
• Previous use of a biologic agent
• Currently taking daily oral steroid doses of greater than 7.5 milligrams (mg)
• Receipt of intra-articular injections within 4 weeks prior to study entry
• Current peptic ulcer disease (PUD)
• Unwilling to stop drinking alcohol (ETOH)
• History of alcohol or substance abuse
• Active infection, or chronic or persistent infection that might worsen with immunosuppressive treatment (e.g., Human Immunodeficiency Virus \[HIV\], hepatitis B virus \[HBV\], hepatitis C virus \[HCV\], tuberculosis \[TB\])
• Interstitial lung disease observed by chest x-ray \[chest radiograph\]
• Known coronary artery disease or significant cardiac arrhythmias or severe congestive heart failure (New York Heart Association \[NYHA\] classes III or IV)
• Definitive diagnosis of another autoimmune rheumatologic disease (e.g., systemic lupus erythematosus \[SLE\], scleroderma, primary Sjögren's syndrome, primary vasculitis)
• History of immunoglobulin E (IgE)-mediated or non-IgE-mediated hypersensitivity or known anaphylaxis to mouse proteins
• History of cancer. Exception: participants with previous resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer within 5 years prior to study entry are not excluded from study eligibility

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator

Study Sites (1)

University of Colorado Health Sciences Center

Denver, Colorado, 80262, United States

Location

Related Publications (4)

• De Vita S, Quartuccio L. Treatment of rheumatoid arthritis with rituximab: an update and possible indications. Autoimmun Rev. 2006 Aug;5(7):443-8. doi: 10.1016/j.autrev.2006.02.007. Epub 2006 Mar 15.

  PMID: 16920570 BACKGROUND

• Eisenberg R, Albert D. B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol. 2006 Jan;2(1):20-7. doi: 10.1038/ncprheum0042.

  PMID: 16932648 BACKGROUND

• Isenberg DA. B cell targeted therapies in autoimmune diseases. J Rheumatol Suppl. 2006 May;77:24-8.

  PMID: 16652442 BACKGROUND

• Looney RJ. B cell-targeted therapy for rheumatoid arthritis: an update on the evidence. Drugs. 2006;66(5):625-39. doi: 10.2165/00003495-200666050-00004.

  PMID: 16620141 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid; Autoimmune Diseases

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue 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

Limitations and Caveats

The trial terminated early due to rituximab's risk-benefit ratio for individuals with early active Rheumatoid Arthritis. Mechanistic samples were not processed and corresponding endpoints were not assessed. Only descriptive statistics are presented.

Results Point of Contact

• Title: Associate Director, Clinical Research Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Christopher Striebich, MD, PhD

  Rheumatology Division, University of Colorado Health Sciences Center

  STUDY CHAIR

• Robert D. D'Ambrosia, MD

  Department of Orthopedics, University of Colorado Health Sciences Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2006
• First Posted: November 8, 2006
• Study Start: November 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: February 12, 2013
• Results First Posted: November 14, 2012

Record last verified: 2013-02

Locations

US (1)