Rituximab in Rheumatoid Arthritis Lung Disease

NCT ID: NCT00578565

Last Updated: 2012-10-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-05-31
• Study Completion Date: 2011-06-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

open label, all subjects will receive rituximab

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

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

Interventions

Rituximab

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

Intervention Type: DRUG

Other Intervention Names

Rituxan; MabThera

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of RA according to the revised 1987 American Rheumatism Association criteria

2. 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

3. Diagnosis of progressive interstitial pneumonia of UIP or NSIP subtype, based on the following criteria

1. Clinical symptoms consistent with interstitial lung disease with onset between 3 months and 36 months prior to screening.

2. 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

3. 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

4. FVC > 50% of predicted value at Screening

5. DLco >30% of predicted value at Screening

5. No change of disease-modifying anti-rheumatic drug (DMARD) treatment within the last 3 months

Exclusion Criteria

1. History of clinically significant environmental or drug exposure known to cause pulmonary fibrosis.

2. Forced expiratory volume in one second (FEV1) FEV1/FVC ratio < 0.6 at screening (pre- or post-bronchodilator).

3. Residual volume > 120% predicted at Screening

4. Evidence of active infection

5. 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

6. History of unstable or deteriorating cardiac or neurologic disease

7. Pregnancy or lactation

8. 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

9. Creatinine > 1.5 X upper limit of normal range (ULN) at Screening

10. Hematology outside of specified limits: white blood cell (WBC) < 2,500/mm^3 or absolute neutrophil count (ANC) < 1500

11. Hematocrit < 27% or > 59%, platelets < 100,000/mm^3 at screening

12. Positive hepatitis B or C serology

13. Any medical condition, which in the opinion of the site principal investigator, may be adversely affected by the participation in this study

14. History of recurrent significant infection or history of recurrent bacterial infections

15. 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

16. Abnormal neurological examination reflective of central nervous disease, including paresis, cognitive impairment and problems with coordination

17. Current enrollment in another clinical trial

18. Fever (>99.5º F)

19. History of previous rituximab administration

20. Receipt of any vaccine, particularly live viral vaccines, within 4 weeks of first study dose

21. Decreased Immunoglobulin G (IgG) and Immunoglobulin M (IgM) levels (below lower limit of normal range)

22. Present or past malignancy

23. History of severe allergic or anaphylactic reaction to administration of humanized or murine monoclonal antibodies

24. Positive human immunodeficiency virus (HIV) serology

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

National Center for Research Resources (NCRR)

NIH

Sponsor Role: collaborator

Eric Matteson

OTHER

Sponsor Role: lead

Responsible Party

Eric Matteson

MD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Eric L Matteson, M.D., M.P.H.

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Mayo Clinic

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

UL1RR024150

Identifier Type: NIH

Identifier Source: secondary_id

View Link

06-007133

Identifier Type: -

Identifier Source: org_study_id