Scarring of the lung, termed pulmonary fibrosis (PF), is a chronic, progressive, and usually fatal disorder. While two anti-fibrotic drugs have been approved for treating PF of unknown cause (idiopathic pulmonary fibrosis or IPF), neither drug is curative, and nearly 40% of patients stop taking the prescribed drug within a year because of side effects. The study includes the use of saracatinib, an investigational drug originally developed to treat certain types of cancers, in the treatment of IPF in a Phase 1b/2a clinical trial. The objectives of this study are to: i) evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics, and to explore the efficacy of saracatinib in IPF; ii) identify biomarkers of Src kinase activity and fibrogenesis linked to pulmonary fibrosis; and iii) explore the application of these biomarkers to assess the anti-fibrotic effect of saracatinib in IPF patients
This is a double blind, randomized, placebo-controlled, single-dose, four-site trial. The trial is a biomarker based, integrated Phase 1b/2a clinical trial involving 100 subjects. One group (n=50) will receive placebo, while the other group (n=50) will receive 125 mg of oral saracatinib once daily. Randomization will be stratified by center. The randomization scheme will be in random blocks of 2 and 4 within each stratum to maintain balance. In the second part of the trial, we will use a simple randomization scheme to achieve the 8:1 randomization across sites. The study is designed to have interim analysis of the drop-out rates when approximately 30% of the randomized patients have achieved the 24-week assessment. Should the drop-out rate be higher than the 20% that is anticipated, a new sample size calculation will be performed to make sure that the power of the study is maintained at 80% . Duration of follow-up will be 28 weeks including 24 weeks of treatment with saracatinib or placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
49
125 mg once daily by mouth for 24 weeks
once daily by mouth for 24 weeks
National Jewish Health
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
Baylor University Medical Center (BUMC)
Dallas, Texas, United States
Safety of saracatinib in IPF as measured by frequency of adverse events
Safety data will be listed and summarized with patient counts and percentages in each treatment arm
Time frame: 24 weeks
Tolerability of saracatinib in IPF as measured by Severity of adverse events
A listing of all adverse events by patient will be presented. This listing will include patient number, adverse event (actual term and preferred term), event stand and end dates, CTCAE grade, relationship to the study drug/procedure, seriousness and outcome. A listing of SAEs will be produced using the similar format. This is not a scale. It is a data capture tool.
Time frame: 24 weeks
Pharmacokinetics of saracatinib in IPF as measured by serum levels
Serum levels of saracatinib
Time frame: 24 weeks
Pharmacodynamics of saracatinib in IPF as measured by change in serum β-CTX
Change in serum β-CTX as a Src kinase dependent biomarker
Time frame: 24 weeks
Efficacy of saracatinib in IPF as measured by change in FVC
Change in FVC from baseline
Time frame: 24 weeks
Efficacy of saracatinib in IPF (HRCT)
Change in HRCT quantitative analysis of the extent of pulmonary fibrosis. The analysis of HRCT data will involve data-driven texture analysis (DTA), a machine learning method capable of automatic detection and quantification of lung fibrosis on HRCT
Time frame: 24 weeks
Efficacy of saracatinib in IPF (DLCO) as measured by change in DLCO
Change in diffusing capacity of the lung for carbon monoxide (DLCO)
Time frame: 24 weeks
Efficacy of saracatinib in IPF (exacerbations) as measured in time to first acute exacerbation
Time to the first acute exacerbation
Time frame: 24 weeks
Efficacy of saracatinib in quality of life in IPF (SGRQ) as measured by total score on SGRQ questionnaire
Total score on the SGRQ questionnaire. St. George's Respiratory Questionnaire (SGRQ) is a 50-item, self-administered, respiratory-specific questionnaire with items covering three domains: symptoms, activities, impacts. Each domain and a total score range from 0-100, with higher scores connoting greater impairment.
Time frame: 24 weeks
Efficacy of saracatinib in quality of life in IPF (L-IPF) as measured by total score on L-IPF questionnaire
Total score on the L-IPF questionnaire. Living with IPF (L-IPF) is an IPF-specific questionnaire whose 43 items cover two modules: symptoms and impacts. A model-based scoring algorithm has been developed via psychometric methods.
Time frame: 24 weeks
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