Current Research & Innovations Thoracic

Interstitial Lung Disease and Pulmonary Fibrosis / AVONEX® Undergoing Multi-center Trial

We are undertaking a research study of an investigational drug called AVONEX® (interferon beta-1a) to inhibit the decline in pulmonary function in patients with Idiopathic Pulmonary Fibrosis (IPF). The principal investigator for this study is Larry L. Schulman, MD. AVONEX (interferon beta-1a) is a recombinant human interferon. In-vitro and in animal studies, interferon beta reduces collagen deposition and fibrosis.

These anti-fibrotic features may reduce the decline in pulmonary function and improve survival in patients with IPF. This is a one year study which will be conducted at approximately 20 centers in the United States and Canada. Subjects will be randomly assigned to receive either placebo, or AVONEX at 15, 30, or 60 mcg, administered twice weekly by IM injection for one year. There will be a schedule of regular physical examinations, blood analysis, pulmonary function tests, health questionnaires, and 2 high resolution CT scans of the chest.

The primary objective of this study is to determine the efficacy of AVONEX in reducing the change in forced vital capacity (FVC) and resting P(A-a) gradient at 12 months in subjects with idiopathic pulmonary fibrosis (IPF).

The secondary objectives of this study are:

• To determine whether AVONEX reduces the accumulation of fibrosis at 12 months in subjects with IPF as measured by high resolution computerized tomography (HRCT) scans.
• To determine whether AVONEX reduces the progression of dyspnea at 12 months in subjects with IPF.
• To determine the safety of AVONEX in subjects with IPF.

The most common side effects associated with AVONEX (interferon beta-1a) have been "flu-like symptoms", muscle aches, fever, chills, and weakness. These symptoms are often relieved with acetaminophen (e.g., Tylenol®) and often lessen during the first few weeks of treatment. Other common side effects in people treated with AVONEX have included headache, general pain, nausea, diarrhea, indigestion, sleeping problems, dizziness, and miscellaneous infections including head colds, sinus infections and bronchitis.

Inclusion Criteria

To be eligible for entry into this study, candidates must meet the following eligibility criteria at the time of enrollment (unless otherwise specified):

• Must be between the ages of 18 and 70 years, inclusive.
• Confirmed diagnosis of IPF. The Advisory Committee to this study will determine eligibility based on data for each subject. Eligibility will be determined by review of clinical history, occupational and environmental exposure, PFTs (pulmonary function tests), HRCT scan, and, if available, lung biopsy slides.
• Progressive disease while taking corticosteroids or a cytotoxic agent.
• On a maintenance dose of prednisone for at least four weeks prior to baseline testing.
• A score of 14 or less on the CRP dyspnea scale.
• Must give written informed consent.

Exclusion Criteria

Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment:

Medical History

• In women with reproductive potential, refusal to take reasonable contraceptive measures.
• Pregnant or nursing women.
• Presence of any medical condition that precludes the use of corticosteroids.
• Abnormal baseline blood tests exceeding any of the limits defined below:
• Alanine transaminase (ALT) or aspartate transaminase (AST) > two times the upper limit of normal (>2x ULN)
• Total white blood cell (WBC) count <2,300/mm³
• Platelet count <80,000/mm³
• Creatinine >2x ULN
• Prothrombin time (PT) >ULN
• End stage IPF subjects, defined by the presence of at least two of the following:
• TLC <45% of predicted
• Single-breath carbon monoxide diffusing capacity of the lung (DLCO), corrected for hemoglobin, <30% of predicted
• Resting P(A-a) gradient >30 mm Hg
• O₂ desaturation <80% with exercise (walking on level ground at own pace for 6 minutes)
• New York Heart Association Class III-IV.
• History of environmental exposure, such as to dust, molds, pigeons, or birds that may result in interstitial lung disease, or a history of ingestion of a drug or an agent known to cause pulmonary fibrosis, such as nitrofurantoin or bleomycin.
• History or evidence of occupational exposure to asbestos.
• History of other lung disease(s) including sarcoidosis, eosinophilic granuloma, Goodpasture's Syndrome, idiopathic pulmonary hemosiderosis, pulmonary alveolar proteinosis, chronic eosinophilic pneumonia, and pulmonary alveolar microlithiasis, and/or HRCT evidence of emphysema or bullous disease occupying >50% of the chest cavity.
• History of connective tissue disease(s) such as rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosis, and scleroderma.
• History of any significant cardiac, hepatic, pulmonary, or renal disease; immune deficiency; or other medical conditions that would preclude therapy with interferon beta.
• History of severe allergic or anaphylactic reactions to human albumin.
• History of a seizure within the 3 months prior to randomization.
• History of suicide ideation or an episode of severe depression within the 3 months prior to randomization.
• History of congestive heart failure.

Treatment History

• Any previous therapy with any interferon beta product.
• Treatment with any immunosuppressive or immunomodulatory agent to treat the underlying disease, except for the agents listed below under the specified condition and oral steroids:
• Cyclophosphamide, Azathioprine,
• Chlorambucil, IVIg, 8 weeks since last treatment
• Methotrexate, Plasma Exchange, 6 weeks since last treatment
• Cyclosporine, 4 weeks since last treatment
• Colchicine, 3 weeks since last treatment
• Prior treatment with any other investigational drug for IPF not listed above, unless approved by the Advisory Committee.
• History of intolerance to corticosteroids that would preclude use during this study

Miscellaneous

• Unwillingness or inability to comply with standard procedures required in this protocol.