Rituximab in Rheumatoid Arthritis Lung Disease

NCT00578565 | Completed Phase 3 Results

• 2 other identifiers: 06-007133UL1RR024150
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This study will examine the course of patients with progressive rheumatoid arthritis associated interstitial lung disease (RA-ILD) treated with rituximab for safety and progression-free survival at 48 weeks. Safety of rituximab therapy in this disease will be assessed through patient history, physical exams and laboratory parameters.

• Twelve male/or female patient with RA-associated lung disease (6 of each nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP) histological subtype) will be enrolled
• The study involves 12 visits over 48 weeks
• Rituximab will be administered intravenously at Day 1 and Day 15 with repeat dosing at six months.

Conditions

Rheumatoid Arthritis; Interstitial Pneumonia

Keywords

Rheumatoid Arthritis; Interstitial Pneumonia; Rheumatology; Rituximab

Outcome Measures

Primary Outcomes (2)

• Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks

  DLco is one pulmonary function measure. For DLco, worsening was defined as decrease of at least 15% and improvement was defined as increase of at least 15%.

  baseline, 48 weeks

• Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks

  FVC is one measure of pulmonary function. For FVC, worsening was defined as decrease of at least 10% and improvement was defined as increase of at least 10%.

  baseline, 48 weeks

Secondary Outcomes (4)

• Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks

  baseline, 48 weeks

• Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks

  baseline, 48 weeks

• Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score.

  baseline, 48 weeks

• Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks

  baseline, 48 weeks

Study Arms (1)

1

EXPERIMENTAL

open label, all subjects will receive rituximab

Drug: Rituximab

Interventions

Rituximab DRUG

Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months.

Also known as: Rituxan, MabThera

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:

• Diagnosis of RA according to the revised 1987 American Rheumatism Association criteria
• Absence of clinical features suggesting infection, neoplasm, sarcoidosis, interstitial lung disease other than UIP or NSIP, other collagen vascular disease, or exposure to known fibrogenic drugs or environmental factors
• Diagnosis of progressive interstitial pneumonia of UIP or NSIP subtype, based on the following criteria
• Clinical symptoms consistent with interstitial lung disease with onset between 3 months and 36 months prior to screening.
• Worsening as demonstrated by any one of the following within the past year:
• \> 10% decrease in Forced Vital Capacity (FVC)
• increasing infiltrates on chest X-ray or High Resolution Computed Tomography (HRCT), or worsening dyspnea at rest or on exertion
• Diagnosis of UIP or NSIP by either of the following:
• Open or video-assisted thoracic surgery (VATS) lung biopsy showing definite or probable UIP or NSIP
• HRCT scan showing definite or probable UIP or NSIP AND abnormal pulmonary function tests (reduced FVC or decreased diffusing capacity of carbon monoxide (DLco) or impaired gas exchange at rest or with exercise) AND insidious onset of otherwise unexplained dyspnea or exertion and bibasilar, inspiratory crackles on auscultation
• FVC \> 50% of predicted value at Screening
• DLco \>30% of predicted value at Screening
• \. No change of disease-modifying anti-rheumatic drug (DMARD) treatment within the last 3 months

You may not qualify if:

• History of clinically significant environmental or drug exposure known to cause pulmonary fibrosis.
• Forced expiratory volume in one second (FEV1) FEV1/FVC ratio \< 0.6 at screening (pre- or post-bronchodilator).
• Residual volume \> 120% predicted at Screening
• Evidence of active infection
• Any pulmonary condition other than UIP/NSIP, which, in the opinion of the site principal investigator, is likely to result in the death of the patient within the next year
• History of unstable or deteriorating cardiac or neurologic disease
• Pregnancy or lactation
• Treatment with cyclophosphamide, cyclosporine, interferon gamma or beta, anti-tumor necrosis factor therapy, anti-interleukin 1 (IL1) therapy or with endothelin receptor blockers within the last 8 weeks; experimental therapy for rheumatoid arthritis
• Creatinine \> 1.5 X upper limit of normal range (ULN) at Screening
• Hematology outside of specified limits: white blood cell (WBC) \< 2,500/mm\^3 or absolute neutrophil count (ANC) \< 1500
• Hematocrit \< 27% or \> 59%, platelets \< 100,000/mm\^3 at screening
• Positive hepatitis B or C serology
• Any medical condition, which in the opinion of the site principal investigator, may be adversely affected by the participation in this study
• History of recurrent significant infection or history of recurrent bacterial infections
• 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 i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening

Sponsors & Collaborators

• Eric Matteson: lead
• Genentech, Inc.: collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid; Lung Diseases, Interstitial

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; Lung Diseases; Respiratory Tract 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

Given the small number of patients, it could not be determined whether patients with nonspecific interstitial pneumonia (NSIP) or usual interstitial pneumonia (UIP) were more likely to respond. Further research is needed in less advanced disease.

Results Point of Contact

• Title: Eric. L. Matteson, M.D.
• Organization: Mayo Clinic

507-284-8450

Study Officials

• Eric L Matteson, M.D., M.P.H.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 19, 2007
• First Posted: December 21, 2007
• Study Start: May 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: October 1, 2012
• Results First Posted: September 25, 2012

Record last verified: 2012-09

Locations

US (2)