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

Study Overview
=================
Brief Summary
-----------------
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 Idiopathic Pulmonary Fibrosis (IPF). There is a 48-week randomized treatment phase followed by an optional, open-label extension phase.

Detailed Description
-----------------
The intent of this study is to evaluate the efficacy and safety of pamrevlumab as monotherapy 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. During the 48-week treatment phase of the study, co-administration of an approved IPF therapy (such as, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, after assessment of potential risks/benefits of such combination with blinded study treatment. Participants who complete the 48-week study will be eligible for an optional, open-label extension phase with continued access to pamrevlumab, regardless of their randomized assignment.

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

Conditions
-----------------
Idiopathic Pulmonary Fibrosis

Intervention / Treatment
-----------------
* Drug: Pamrevlumab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/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 ≥25% and ≤90%. Not currently receiving treatment for IPF with an approved therapy for IPF (such as, 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, as evidenced by spirometry or HRCT. 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. Other types of respiratory diseases that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study, including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall. Certain medical conditions, that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study (such as, myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or cancers). Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening. 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 (such as, 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
-----------------
Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pamrevlumab<br>Treatment phase: Pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks. Open-label extension phase: Pamrevlumab 30 mg/kg administered by intravenous infusion, every 3 weeks for up to 48 weeks | Drug: Pamrevlumab<br>* Sterile solution for injection<br>* Other names: FG-3019;|
| Experimental: Placebo<br>Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks | Drug: Placebo<br>* Sterile solution for injection<br>|

What is the study measuring?
-----------------
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 | Defined as absolute FVC percent predicted (FVCpp) decline of ≥10% or death, whichever occurs first | Up to Week 48 | 
| Change from Baseline to Week 48 in Quantitative Lung Fibrosis (QLF) Volume |  | Baseline, Week 48 | 
| Time to Any Component of the Clinical Composite Endpoint, Whichever Occurs First: Acute IPF Exacerbation, Respiratory Hospitalization, or Death |  | Up to Week 48 | 
| Time to First Acute IPF Exacerbation |  | Up to Week 48 | 
| Time to All-Cause Mortality |  | Up to Week 48 | 
| Time to First Respiratory Hospitalization |  | Up to Week 48 | 

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