Rituximab in Rheumatoid Arthritis Lung Disease

This study has been completed.
Sponsor:
Collaborators:
Genentech
Information provided by (Responsible Party):
Eric Matteson, Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00578565
First received: December 19, 2007
Last updated: September 25, 2012
Last verified: September 2012
  Purpose

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.

Condition Intervention Phase
Rheumatoid Arthritis
Interstitial Pneumonia
Drug: Rituximab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Rituximab for the Treatment of Rheumatoid Arthritis-Associated Interstitial Pneumonia: A Pilot Study

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Change in Diffusion Capacity for Carbon Monoxide (DLco) From Baseline to 48 Weeks [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    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%.

  • Change in Forced Vital Capacity (FVC) From Baseline to 48 Weeks [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    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%.


Secondary Outcome Measures:
  • Change in Lung Fibrosis Score as Observed on High Resolution Computerized Tomography (HRCT) Scans, From Baseline to 48 Weeks [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    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.

  • Assessment of RA Disease Activity Scores as Measured by the DAS28 Score at Baseline and 48 Weeks [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]

    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.


  • Change in RA Disease Activity From Baseline to 48 Weeks Using the DAS28 Score. [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]

    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.


  • Percentage of Change in Health Associated Quality of Life From Baseline to 48 Weeks [ Time Frame: baseline, 48 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 10
Study Start Date: May 2007
Study Completion Date: June 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
open label, all subjects will receive rituximab
Drug: Rituximab
Rituximab 1000 mg. I.V.on each days 1 and 15 with repeat dosing at 6 months.
Other Names:
  • Rituxan
  • MabThera

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00578565

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Eric Matteson
Genentech
Investigators
Principal Investigator: Eric L Matteson, M.D., M.P.H. Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Eric Matteson, MD, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00578565     History of Changes
Other Study ID Numbers: 06-007133, UL1RR024150
Study First Received: December 19, 2007
Results First Received: May 21, 2012
Last Updated: September 25, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
Rheumatoid Arthritis
Interstitial Pneumonia
Rheumatology
Rituximab

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Pneumonia
Lung Diseases, Interstitial
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 23, 2014