Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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The primary objectives of this study are to determine the effect of simtuzumab (GS-6624) on progression-free survival (PFS) as determined by either a categorical decline in forced vital capacity (FVC) or all-cause mortality, in all participants enrolled or in a subset of participants who are classified as lysyl oxidase-like-2 (LOXL2) high based on a prespecified level in serum at baseline.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Simtuzumab
* Drug: Simtuzumab placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subjects from 45 to 85 years of age Definite IPF within 3 years prior to screening Be able to walk at least 50 meters Key Exclusion Criteria: Significant diseases other than IPF Obstructive lung disease Aortic aneurysm greater than or equal to 3.5 cm in diameter Treatment with immunosuppressive, cytotoxic, or antifibrotic drugs < 28 days prior to randomization are not permitted. N-acetylcysteine is permitted provided the individual has been on a stable dose for > 4 weeks prior to screening Concomitant use of pirfenidone or nintedanib must be in accordance with the approved prescribing instructions in the country where the site is located Individuals actively listed for lung transplant are excluded. However individuals at transplant centers with long waiting times (greater than 1 year) may be permitted to enter the study after discussion with Medical Monitor. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 85 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Simtuzumab<br>Participants will receive simtuzumab for up to 254 weeks. | Drug: Simtuzumab<br>* 125 mg/mL single-dose vials administered subcutaneously once a week<br>* Other names: GS-6624;|
| Placebo Comparator: Simtuzumab Placebo<br>Participants will receive simtuzumab placebo for up to 254 weeks. | Drug: Simtuzumab placebo<br>* Simtuzumab placebo single-dose vials administered subcutaneously once a week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival (PFS) was defined as the categorical decrease in forced vital capacity (FVC) % predicted (≥ 10% relative decrease in FVC and ≥ 5% absolute decrease in FVC from baseline) with confirmation at a consecutive visit at least 2 weeks later using the same criteria. | Up to 148 weeks | 
| PFS Among the Participants With sLOXL2 ≥ 50th Percentile |  | Up to 148 weeks | 
| PFS Among the Participants With sLOXL2 ≥ 75th Percentile |  | Up to 148 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival was defined as the time from randomization date to death that occurred prior to the last dose date plus 30 days. | Up to 151 weeks | 
| Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile |  | Up to 151 weeks | 
| Overall Survival Among the Participants With sLOXL2 ≥ 75th Percentile |  | Up to 151 weeks | 
| Relative Change From Baseline in FVC % Predicted | FVC was defined as the volume of air (liters) that can forcibly be blown out after taking a full breath. FVC % predicted was defined as FVC % of the participant divided by the average FVC % in the population for any person of similar age, sex, and body composition. Adjusted means were from mixed model repeated measures (MMRM) model with baseline FVC % predicted, sLOXL2 level, concomitant pirfenidone/nintedanib use (never vs. ever), treatment, visit, and treatment-by-visit interaction terms, including all data up to Week 130 The relative change was calculated as 100% * ( value at later time point minus value at baseline ) / value at baseline, with lower values indicating a decrease and higher values indicating an increase. | Weeks 54, 106, and 130 | 
| Definite Acute Exacerbations of IPF Among Adjudicated Respiratory Hospitalizations |  | Up to 148 weeks | 
| Number of Adjudicated Respiratory Hospitalizations (ARP) Among Total Hospitalizations |  | Up to 148 weeks | 
| Number of Participants Experiencing Adjudicated Respiratory Deaths Among Those With Adjudicated Death |  | Up to 148 weeks | 
| Absolute Change From Baseline in 6 Minute Walk Distance (6MWD) | Adjusted means were from MMRM model with baseline 6MWD, FVC % predicted, sLOXL2 level, concomitant pirfenidone/nintedanib use (never vs. ever), treatment, visit, and treatment-by-visit interaction terms, including all data up to Week 130. The absolute change was calculated as value at later time point minus value at baseline, with lower values indicating a decrease and higher values indicating an increase. | Weeks 58, 106, and 130 | 
| Absolute Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score | The SGRQ is a disease-specific questionnaire designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency & severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations. The absolute change was calculated as value at later time point minus value at baseline, with lower values indicating a decrease and higher values indicating an increase. | Week 58, 106, and 130 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Idiopathic, Pulmonary, Fibrosis, IPF