Clinical trial NCT00578565: Rituximab in Rheumatoid Arthritis Lung Disease
Official title: Rituximab for the Treatment of Rheumatoid Arthritis-Associated Interstitial Pneumonia: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Interstitial Pneumonia
Keywords: Rheumatoid Arthritis
Interstitial Pneumonia
Rheumatology
Rituximab
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: National Center for Research Resources (NCRR)
First posted: 2007-12-21
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks
timeFrame: baseline, 48 weeks
measure: Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks
timeFrame: baseline, 48 weeks
Secondary outcomes:
measure: Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks
timeFrame: baseline, 48 weeks
measure: Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks
timeFrame: baseline, 48 weeks
measure: Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score.
timeFrame: baseline, 48 weeks
measure: Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks
timeFrame: baseline, 48 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Eric L Matteson, M.D., M.P.H.
role: PRINCIPAL_INVESTIGATOR
References: