Rituximab in Rheumatoid Arthritis Lung Disease

Rheumatoid Arthritis Clinical Trial

Official title:

Rituximab for the Treatment of Rheumatoid Arthritis-Associated Interstitial Pneumonia: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00578565
• Other study ID #: 06-007133
• Secondary ID: UL1RR024150
• Status: Completed
• Phase: Phase 3
• First received: December 19, 2007
• Last updated: September 25, 2012
• Start date: May 2007
• Est. completion date: June 2011

Study information

• Verified date: September 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: June 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Interstitial Pneumonia
• Lung Diseases, Interstitial
• Pneumonia
• Rheumatoid Arthritis

Intervention

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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Eric Matteson	Genentech, Inc., National Center for Research Resources (NCRR)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks	Three serial HRCT scans of each patient were scored independently and simultaneously by two core radiologists, who were blinded to the sequence in which three scans were obtained (at screening, 24 and 48 weeks). The HRCT scoring sheet scored different domains of abnormality such as, linear opacities, consolidation, ground-glass density, etc. Radiographers reported composite impression based on scoring according to worsening, no worsening or improvement of relevant domains.	baseline, 48 weeks	No
Secondary	Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks	The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.; Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.	baseline, 48 weeks	No
Secondary	Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score.	The DAS28 score is a measure of RA disease activity calculated using variables such as swollen joint count, the Erythrocyte Sedimentation Rate (ESR) and patient reported assessment of health.; Using this data, the DAS28 calculation provides a number on a scale from 0-10 indicating the current activity of a patient's RA. A DAS28 score above 5.1 means high disease activity whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a DAS28 score lower than 2.6.	baseline, 48 weeks	No
Secondary	Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks	The percentage change from baseline to week 48 in a participant's perception of the impact of health on his or her quality of life was collected on the Health Assessment Questionnaire (HAQ). The HAQ measures a person's ability to function with arthritis. The questionnaire is divided into 8 categories (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip and Activities) which include several questions for each category. The category score is determined by the highest score of the set of questions for each category. The disability score is determined by adding the scores for all categories and dividing by 8. The disability scale ranges from 0 (best - without any difficulty) to 3 (worst - unable to do much).	baseline, 48 weeks	No

External Links

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