Phase 3
N=10
Rituximab in Rheumatoid Arthritis Lung Disease
Rheumatoid Arthritis · Interstitial Pneumonia
Bottom Line
View on ClinicalTrials.gov: NCT00578565 ↗Enrolled (actual)
10
Serious AEs
20.0%
Results posted
Sep 2012
Primary outcome: Primary: Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks — 4; 2; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Rituximab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Eric Matteson
- Primary completion
- Jun 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks |
4; 2; 1 | — |
| PRIMARY Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks |
4; 2; 1 | — |
| SECONDARY Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks |
5; 1; 1 | — |
| SECONDARY Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks |
5.5; 3.3 | — |
| SECONDARY Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score. |
-31.8 | — |
| SECONDARY Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks |
85.9 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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
Exclusion Criteria
- History of clinically significant environmental or drug exposure known to cause pulmonary fibrosis.
- Forced expiratory volume in one second (FEV1) FEV1/FVC ratio 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) 59%, platelets 99.5º F)
- History of previous rituximab administration
- Receipt of any vaccine, particularly live viral vaccines, within 4 weeks of first study dose
- Decreased Immunoglobulin G (IgG) and Immunoglobulin M (IgM) levels (below lower limit of normal range)
- Present or past malignancy
- History of severe allergic or anaphylactic reaction to administration of humanized or murine monoclonal antibodies
- Positive human immunodeficiency virus (HIV) serology
Data sourced from ClinicalTrials.gov (NCT00578565). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.