Rituximab in Rheumatoid Arthritis Lung Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00578565
• Date of registration: 19/12/2007
• Prospective Registration: No
• Primary sponsor: Eric Matteson
• Public title: Rituximab in Rheumatoid Arthritis Lung Disease
• Scientific title: Rituximab for the Treatment of Rheumatoid Arthritis-Associated Interstitial Pneumonia: A Pilot Study
• Date of first enrolment: May 2007
• Target sample size: 10
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00578565
• Study type: Interventional
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Eric L Matteson, M.D., M.P.H.
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Interstitial Pneumonia

Rheumatoid Arthritis

Intervention(s)

Drug: Rituximab

Primary Outcome(s)

Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks [Time Frame: baseline, 48 weeks]

Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks [Time Frame: baseline, 48 weeks]

Secondary Outcome(s)

Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks [Time Frame: baseline, 48 weeks]

Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score. [Time Frame: baseline, 48 weeks]

Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks [Time Frame: baseline, 48 weeks]

Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks [Time Frame: baseline, 48 weeks]

Secondary ID(s)

06-007133

UL1RR024150

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Center for Research Resources (NCRR)

Genentech, Inc.

Results

• Results available: Yes
• Date Posted: 25/09/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00578565