Clinical trial NCT01969409: Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis
Official title: Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis (ART-IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ambulatory IPF
Keywords: Lung
Fibrosis
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2013-10-25
Enrollment: 58
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent research studies have suggested that proteins called antibodies that are produced by the immune system might be involved in the lung damage of idiopathic pulmonary fibrosis (IPF). Antibodies produced by the immune system normal help to fight infections by attacking bacteria and viruses without harming our own tissues. In patients with IPF, there is evidence that certain antibodies (called autoantibodies) attack the lung and contributes to the injury and scarring that occurs in IPF. Our recent studies have found that many IPF patients appear to have excessive autoantibody levels in blood and lungs that might make their disease worse.

Rituximab is a medication approved by the Food and Drug Administration (FDA) for the treatment of autoantibody diseases such as rheumatoid arthritis. Rituximab works by destroying B cells, a type of white blood cell, called a B-lymphocyte, which produce autoantibodies. In this research study, rituximab will be given into a vein to reduce the autoantibody levels that we believe might be contributing to the lung damage in IPF.

This study is being conducted to determine if rituximab provides beneficial effects for IPF patients by decreasing further lung injury.

Detailed description: This is a double-blinded, Phase II trial in which 58 ambulatory IPF patients at any of four medical centers (University of Pittsburgh, University of Chicago, Geisinger Medical Center, and Temple University) will be randomized equally to 1. placebo or 2. two doses of rituximab 1 gm i.v., with a 14 day interval inbetween doses.

Subjects will be followed for 9 months.

Eligibility criteria: Inclusion Criteria:

Ambulatory patients with a diagnosis of IPF, not established \>5 years from the enrollment date, that fulfills American Thoracic Society (ATS)/European Thoracic Society (ETS) Consensus Criteria.

Ability and willingness to give informed consent. Presence of autoantibodies against Hepatoma-2 (HEp-2) cells, the assay for the primary endpoint.

Age 50-85 y.o.

Exclusion Criteria:

Diagnoses of current infection, proven or suspected by participating physicians based upon their clinical assessments.

Presence of active hepatitis B or C, or HIV infection. Presence of positive CONVENTIONAL autoimmune serologic tests, e.g., Antinuclear Antibodies (ANA), Rheumatoid Factor (RF), Anti-Ro, Anti-LA, Anti-Ribonucleoprotein Antibodies (RNP), Anti-Jo-1.

History of reaction to murine-derived products or any of the trial medications, or prior exposures to human-murine chimeric antibodies.

Malignancy, excluding basal or squamous cell skin cancer and low-risk prostate cancer, defined as stage T1 or T2a with Prostate-Specific Antigen (PSA) less than 10 ng/dl.

Unwillingness to complete post-treatment surveillance for 9 months. Diagnosis of major morbidities (aside from IPF) expected to interfere with subjects' study participation for 9 months.

Treatment for \>5 days within the preceding month with \>10 mg. prednisone (or equivalent corticosteroid) or any treatment during the preceding month with a potent cellular immunosuppressant (e.g., cyclophosphamide, methotrexate, mycophenolate, azathioprine, calcineurin inhibitors, etc.).

Uncontrolled diabetes or hypertension that preclude safe treatment with methylprednisolone.

Concurrent participation in other experimental trials.

Pregnancy or unwillingness to use contraception during the duration of the study among female participants with child-bearing potential.

Ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) \<70% of predicted values.

Primary outcomes:
measure: Autoantibodies to Human Epidermoid (HEp)-2 Cells
timeFrame: baseline to 9 months
Secondary outcomes:
measure: Changes in Anti-Heat Shock Protein 70 (HSP70) Autoantibodies
timeFrame: baseline to 9 months
measure: Changes in Forced Vital Capacity (FVC)
timeFrame: baseline thru 9 months
measure: Number of Adverse Events (AE)
timeFrame: during the 9 months of observation
measure: Number of Acute Exacerbations
timeFrame: during the study duration of 9 months
measure: Absolute Survival Percentage
timeFrame: during 9 months of observation
measure: Transplant-Free Survival
timeFrame: during 9 months of observation
measure: Hospitalizations
timeFrame: during 9 months of observation
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnestoa
state: Minnesota
city: Danville
country: United States
facility: Geisinger Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: University of Alabama at Birmingham
name: Steven R Duncan, MD
role: PRINCIPAL_INVESTIGATOR
References: