The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00075998
• Date of registration: 12/01/2004
• Prospective Registration: No
• Primary sponsor: InterMune
• Public title: The INSPIRE Trial: A Study of Interferon Gamma-1b for Idiopathic Pulmonary Fibrosis (IPF)
• Scientific title: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of the Safety and Efficacy of Interferon Gamma-1b in Patients With Idiopathic Pulmonary Fibrosis (The INSPIRE Trial)
• Date of first enrolment: December 2003
• Target sample size: 826
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00075998
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: InterMune, Inc.
• Affiliation: Medical Information

Key inclusion & exclusion 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




Age minimum: 40 Years
Age maximum: 79 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Lung Disease

Idiopathic Pulmonary Fibrosis

Pulmonary Fibrosis

Intervention(s)

Drug: Interferon gamma-1b ("Actimmune")

Primary Outcome(s)

Survival time from randomization to treatment completion visit, or, end of treatment period, or, last known vital status. [Time Frame: 3.5 years]

Secondary Outcome(s)

Total number of days without hospitalization resulting from respiratory admission diagnosis (ongoing assessment up to end of study). [Time Frame: 3.5 years]

Changes from baseline measurement to week 96 measurement in the following (measured every 24 weeks): 6-minute walk test, shortness of breath [Time Frame: 96 weeks]

Lung transplant-free survival time (ongoing assessment up to end of study). [Time Frame: 3.5 years]

Secondary ID(s)

GIPF-007

Source(s) of Monetary Support

Please refer to primary and secondary sponsors