Clinical trial NCT00075998 (phase 3, status: terminated)
Conditions: idiopathic pulmonary fibrosis, lung disease, pulmonary fibrosis
ICD codes: J84.112, J84.115, M05.10, M05.111, M05.112, M05.119, M05.121, M05.122, J84.10, J84.112, E84.0, J84.178
Drugs: interferon gamma-1b ("actimmune")
SMILES: CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1
Reason stopped: 
    test drug showed lack of benefit at interim analysis
  
Eligibility criteria:

        Inclusion criteria:

          -  Clinical symptoms consistent with IPF of >= 3 months duration

          -  Diagnosis of IPF within 48 months before randomization

          -  Age 40 through 79, inclusive

          -  High-resolution computed tomographic scan (HRCT) showing definite IPF. For patients
             with surgical lung biopsy showing definite or probable usual interstitial pneumonia
             (UIP), the HRCT criterion of probable IPF is sufficient.

          -  For patients aged < 50 years: open or video-assisted thoracoscopic (VATS) lung biopsy
             showing definite or probable UIP within 48 months before randomization. In addition,
             there are no features supporting an alternative diagnosis on transbronchial biopsy or
             bronchoalveolar lavage (BAL) if performed.

          -  For patients aged < 50 years: At least one of the following diagnostic findings, as
             well as the absence of any features on specimens resulting from any of these
             procedures that support an alternative diagnosis, within 48 months before
             randomization:

               -  Open or VATS lung biopsy showing definite or probable UIP

               -  Transbronchial biopsy showing no features to support an alternative diagnosis

               -  BAL showing no features to support an alternative diagnosis IPF Disease Severity
                  and Progression

          -  FVC >= 55% of predicted value (post administration of bronchodilator)

          -  Hemoglobin (Hb)-corrected carbon monoxide diffusing capacity/carbon monoxide transfer
             capacity (DLCO/TLCO) >= 35% of predicted value

          -  At least one of either FVC or Hb-corrected DLCO/TLCO <= 90% of predicted value

          -  IPF disease progression evidenced by one or more of the following within the past year
             and the absence of evidence of improvement in the past year:

               -  Absolute decrease of >= 10% in FVC

               -  Absolute decrease of >= 15% in DLCO/TLCO

               -  Evidence of clinically significant worsening on chest X ray or HRCT

               -  Significant worsening of dyspnea

          -  Distance walked >= 150 meters (492 feet) with O2 saturation >= 83% on <= 6 L/min of O2
             during the 6 Minute Walk Test (6MWT) oxygen titration procedure

        Exclusion criteria:

          1. Not a suitable candidate for enrollment or unlikely to comply with the requirements of
             this study, in the opinion of the Principal Investigator (PI)

          2. Forced expiratory volume in the first second (FEV1)/FVC ratio < 0.6 (after
             administration of bronchodilator)

          3. Residual volume (RV) > 140% of predicted (before administration of bronchodilator)

          4. History of clinically significant environmental exposure known to cause pulmonary
             fibrosis (including but not limited to drugs, asbestos, beryllium, radiation, domestic
             birds)

          5. Known explanation for interstitial lung disease, including but not limited to
             radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans
             organizing pneumonia, and cancer

          6. Diagnosis of any connective tissue disease, including but not limited to scleroderma,
             systemic lupus erythematosus, and rheumatoid arthritis

          7. Clinical evidence of active infection, including but not limited to bronchitis,
             pneumonia, sinusitis, urinary tract infection, and cellulitis

          8. On a lung transplantation waiting list at time of randomization

             Medical Exclusions:

          9. Any history of malignancy likely to result in death, significant disability, or likely
             to require significant medical or surgical intervention within the next 3 years. This
             does not include minor surgical procedures for localized carcinoma (e.g., basal cell
             carcinoma)

         10. Any condition other than IPF which, in the opinion of the PI, is likely to result in
             the death of the patient within the next 3 years

         11. History of unstable or deteriorating cardiac, vascular, or neurologic disease within
             the previous 6 months, including but not limited to the following:

               -  Myocardial infarction, unstable angina pectoris, coronary artery bypass surgery,
                  or coronary angioplasty

               -  Congestive heart failure requiring hospitalization

               -  Uncontrolled arrhythmias

               -  Thromboembolic event (e.g., deep vein thrombosis, pulmonary embolism)

               -  Transient ischemic attacks (TIAs) or cerebral vascular accident

         12. Any condition, which, in the opinion of the investigator, might be significantly
             exacerbated by the known side effects, (e.g., flu-like syndrome) associated with the
             administration of IFN g 1b

         13. History of any of the following medical conditions:

               -  Multiple sclerosis

               -  Seizures within the past 10 years or taking anti seizure medication

               -  Severe or poorly controlled diabetes

         14. Pregnancy or lactation. Females of childbearing potential are required to have a
             negative serum pregnancy test before treatment and must agree to practice abstinence
             or prevent pregnancy by at least a barrier method of birth control for the duration of
             the study

         15. Inability to tolerate nonsteroidal anti-inflammatory drugs (NSAIDS) or acetaminophen
             (paracetamol)

         16. History of ethanol abuse in the past 2 years

         17. Known hypersensitivity to IFN-g or closely related interferons or to any component of
             the study treatment

         18. Presence of human immunodeficiency virus (HIV) or chronic viral hepatitis

             Laboratory Exclusions:

         19. Any of the following liver function test criteria above specified limits:

             Total bilirubin > 1.5 x upper limit of normal (ULN); aspartate or alanine
             aminotransferases (AST/SGOT or ALT/SGPT) > 2 x ULN; alkaline phosphatase > 2 x ULN; or
             albumin < 3.0 mg/dL

         20. Any of the following hematology test criteria outside of specified limits: WBC <
             2,500/mm3, hematocrit < 30% or > 59%, platelets < 100,000 /mm3

         21. Creatinine > 1.5 x ULN

             Concomitant Therapy Exclusions:

         22. Prednisone therapy (prednisone or equivalent, with dose adjusted for potency) in
             excess of 0.125 mg/kg ideal body weight (IBW) per day or in excess of 0.25 mg/kg IBW
             every other day. Patients will also be excluded if they were not on a stable dose of
             corticosteroid therapy for at least 28 days prior to screening.

         23. Prior treatment with IFN g 1b

         24. Investigational therapy (i.e., agents that are not approved by local regulatory
             agencies) for any indication within 28 days prior to screening

         25. The following therapies are excluded within 28 days prior to screening:

               -  Investigational therapy for IPF, including pirfenidone

               -  Any cytotoxic/immunosuppressive agent other than corticosteroids (including but
                  not limited to azathioprine, cyclophosphamide, methotrexate, cyclosporine)

               -  Any cytokine modulators (including but not limited to etanercept, infliximab)

               -  Any therapy targeted to treat IPF (including but not limited to d penicillamine,
                  colchicine, bosentan, N-acetyl-cysteine [NAC])