Efficacy and Safety of SAR156597 in the Treatment of Idiopathic Pulmonary Fibrosis

Study Overview
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Brief Summary
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Primary Objective: To evaluate, in comparison with placebo, the efficacy of 2 dose levels/regimens of SAR156597 administered subcutaneously during 52 weeks on lung function of participants with Idiopathic Pulmonary Fibrosis (IPF). Secondary Objectives: To evaluate the efficacy of 2 dose levels/regimens of SAR156597 compared to placebo on IPF disease progression. To evaluate the safety of 2 dose levels/regimens of SAR156597 compared to placebo in participants with IPF.

Detailed Description
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The total study duration of study was expected up to 68 weeks (screening period of 4 weeks, treatment period of 52 weeks, and 12 weeks of follow up).

Official Title
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Efficacy and Safety of SAR156597 in the Treatment of Idiopathic Pulmonary Fibrosis (IPF): A Randomized, Double-blind, Placebo-controlled, 52-week Dose-ranging Study

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: SAR156597
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria : Adult male or female participants. Documented diagnosis of IPF according to the current 2011 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/ American Latin Thoracic Association (ATS/ERS/JRS/ALAT) guidelines. Signed written informed consent. Exclusion criteria: Age less than or equal to 40 years. IPF disease diagnosis greater than 5 years. Forced vital capacity (FVC) less than (<) 40 percent (%) of predicted value. Carbon monoxide diffusing lung capacity (DLCO) corrected for hemoglobin <30% of predicted value. Severe chronic obstructive bronchitis as characterized by forced expiratory volume in 1 second /forced vital capacity (FEV1/FVC) <0.70. Need for 24 hours of oxygen therapy or oxygen saturation <88% after 10 minutes breathing ambient air at rest. Known diagnosis of significant respiratory disorders other than IPF. Pulmonary artery hypertension requiring a specific treatment. Currently listed and/or anticipated for lung transplantation within the next 6 months (on an active list). History of vasculitis or connective tissue disorders. Known human immunodeficiency virus or chronic viral hepatitis. Participants with active tuberculosis or incompletely treated latent tuberculosis infection. Use of any cytotoxic/immunosuppressive agent including but not limited to azathioprine, cyclophosphamide, methotrexate, and cyclosporine within 4 weeks prior to screening. Use of any cytokine modulators (etanercept, adalimumab, efalizumab, infliximab, golimumab, certolizumab, rituximab) within 12 weeks or 5 half-lives of screening (24 weeks for rituximab and 24 months for alefacept). Use of any investigational drug within 1 month of screening, or 5 half-lives, if known ( whichever was longer), or within 12 weeks for stem cell therapy. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo qw<br>Participants received one injection of placebo (matched to SAR156597) subcutaneously once every week (qw) for 52 weeks. | Drug: placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>|
| Experimental: SAR156597 200 mg q2w<br>Participants received one injection of SAR156597 200 mg subcutaneously once every 2 weeks (q2w) alternating with placebo (matched to SAR156597) for 52 weeks. | Drug: SAR156597<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>|
| Experimental: SAR156597 200 mg qw<br>Participants received one injection of SAR156597 200 mg subcutaneously qw for 52 weeks. | Drug: SAR156597<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 | FVC is a standard pulmonary function parameter measured by spirometry and used to quantify respiratory capacity (inspiration and expiration). It is a widely used objective measure of disease status in participants with Idiopathic Pulmonary Fibrosis (IPF). The primary variable was recorded as percent (%) of predicted value, which takes into account the height, gender, and age of the participant. The outcome measure measured the change in lung function from baseline at week 52. | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression: Kaplan-Meier Estimates of Probability of Disease Progression at Week 52 | Disease progression was defined as the time from randomization to the first occurrence of any of the following events: decrease in absolute percent predicted FVC greater than or equal to (>=) 10%, decrease in absolute percent predicted Carbon monoxide diffusing lung capacity >=15%, lung transplant, or death. The median time to disease progression was not estimated because the number of occurrence of events was too low in the SAR156597 200 mg arms. | From randomization to disease progression (up to Week 52) | 
| Time to Event: Kaplan-Meier Estimates of Probability of All Cause Mortality (Deaths) at Week 52 | All-cause mortality was considered for this outcome measure which was defined as the time from randomization to the date of death. The median time to event was not estimated because the number of all cause mortality was too low in the SAR156597 200 mg arms. | From randomization up to Week 52 |