Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with IPF.

Detailed Description
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This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of pamrevlumab in participants with IPF. Participants who are not being treated with approved IPF therapies (that is, nintedanib or pirfenidone) may be eligible for screening. Examples of reasons participants may not be treated with approved IPF therapies include but are not limited to: Intolerant or not responsive to approved IPF therapies Ineligible to receive these therapies Participant voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks NOTE: No participant should discontinue an approved IPF therapy for the purpose of enrolling in this study. The study consists of the following study periods: Main (double blind, placebo-controlled) phase: Screening period: Up to 6 weeks Treatment period: 48 weeks Optional, open-label extension (OLE) phase of pamrevlumab: o Access to pamrevlumab will be available until the last participant completes 48 weeks of treatment in the OLE phase, or pamrevlumab is commercially available for the indication of IPF, or the Sponsor decides to end the OLE phase, whichever occurs first. Follow-up period/final safety assessments: 28 days after last dose 60 days after last dose: follow-up phone call, for a final safety assessment During the treatment period, co-administration of an approved IPF therapy (that is, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, provided that the Investigator assesses the potential risks/benefits of combining approved IPF therapies with blinded study treatment. Participants who discontinue study treatment for any reason should be encouraged to remain in the study and be followed for all study visits and assessments. Participants who complete the Week 48 visit of the main study (regardless of the number of study drug infusions received) will be eligible to participate in the optional OLE phase of the study that offers continuing access to pamrevlumab regardless of randomization assignment in the main study.

Official Title
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A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Pamrevlumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of IPF as defined by American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japan Radiological Society (JRS)/Latin American Thoracic Association (ALAT) guidelines within the past 7 years prior to study participation. High-resolution computed tomography (HRCT) scan at screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing. FVCpp value >45% and <95% at screening and Day 1 (prior to randomization). Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted and corrected by hemoglobin (Hb) value ≥25% and ≤90% at screening (determined locally). Not currently receiving treatment for IPF with an approved therapy (that is, pirfenidone or nintedanib) for any reason, including prior intolerance or lack of response to an approved IPF therapy, or choice to forego treatment with an approved IPF therapy after a full discussion with the Investigator regarding risks/benefits of such therapy. Key Exclusion Criteria: Previous exposure to pamrevlumab. Evidence of significant obstructive lung disease. Female participants who are pregnant or nursing. Smoking within 3 months of screening and/or unwilling to avoid smoking throughout the study. Interstitial lung disease other than IPF. Sustained improvement in the severity of IPF during the 12 months prior to screening. History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall. Medical conditions (for example, myocardial infarction [MI]/stroke within the past 6 month), or logistical challenges that in the opinion of the Investigator preclude the participant's adequate participation in the study. Acute IPF exacerbation during screening or randomization. Use of any investigational drugs or unapproved therapies, or participation in any clinical trial with an investigational new drug within 30 days prior to screening. Or use of approved IPF therapies (that is, pirfenidone or nintedanib) within 1 week prior to screening. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.

Ages Eligible for Study
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Minimum Age: 40 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamrevlumab<br>Pamrevlumab 30 mg/kg by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks | Drug: Pamrevlumab<br>* Pamrevlumab will be administered per dose and schedule specified in the arm description.<br>* Other names: FG-3019;|
| Experimental: Placebo<br>Placebo matching to pamrevlumab by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks | Drug: Placebo<br>* Placebo matching to pamrevlumab will be administered per schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Forced Vital Capacity (FVC) at Week 48 |  | Baseline, Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression | Time to disease progression was defined as absolute percent predicted FVC (FVCpp) decline of ≥10% or death, whichever occurs first. | Baseline to Week 48 | 
| Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48 |  | Baseline, Week 48 | 
| Time to Any Component of the Clinical Composite Endpoint, Whichever Occurs First: Acute IPF Exacerbation, Respiratory Hospitalization, or Death |  | Baseline to Week 48 | 
| Time to First Acute IPF Exacerbation During Study |  | Baseline to Week 48 | 
| Time to All-cause Mortality During Study |  | Baseline to Week 48 | 
| Time to First Respiratory Hospitalizations During Study |  | Baseline to Week 48 | 

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