Autoantibody Reduction Therapy in Patients With Idiopathic Pulmonary Fibrosis
Condition: Ambulatory IPF
MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis
Intervention: Rituximab; Placebo
Intervention description: i.v. rituximab given on two occasions 14 days apart.; Subjects randomized to placebo will receive two i.v. doses of 5% dextrose in water (D5W) in the same schedule as the rituximab subjects. The D5W and rituximab preparations will be indistinguishable.
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 58.0
Sex: All
Minimum age: 50 Years
Maximum age: 85 Years
Healthy volunteers: No
Keywords: Lung; Fibrosis

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.
    

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.