Zephyrus II: Efficacy and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
- Registration Number
- NCT04419558
- Lead Sponsor
- FibroGen
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 372
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks Pamrevlumab Pamrevlumab 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
- Primary Outcome Measures
Name Time Method DB Period: Change From Baseline in FVC at Week 48 Baseline, Week 48 FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were analyzed using mixed model repeated measures (MMRM).
- Secondary Outcome Measures
Name Time Method DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First Up to Week 48 The components of the clinical composite endpoints included acute idiopathic pulmonary fibrosis (IPF) exacerbation, respiratory hospitalization, or death. 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.
DB Period: Time to First Acute IPF Exacerbation Up to Week 48 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.
DB Period: Time to All-Cause Mortality Up to Week 48 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.
DB Period: Time to Disease Progression Up to Week 48 Time to disease progression was defined as time from randomization to either the first occurrence of an absolute FVC percent predicted (FVCpp) decline of ≥10% from baseline or death, whichever occurred first. 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.
DB Period: Time to First Respiratory Hospitalization Up to Week 48 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.
DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48 Baseline, Week 48 The QLF volume is calculated as QLF=total lung capacity volume (TLC) \* % of quantitative lung fibrosis for fibrosis of the whole lung. LS mean and SE were analyzed using MMRM.
Trial Locations
- Locations (157)
UAB Lung Health Center
🇺🇸Birmingham, Alabama, United States
UC San Francisco
🇺🇸San Francisco, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
St. Francis Medical Center
🇺🇸Clearwater, Florida, United States
Pulmonary Disease Specialists d/b/a PDS Research
🇺🇸Kissimmee, Florida, United States
TGH/USF Center for Advanced Lung Disease and Lung Transplant
🇺🇸Tampa, Florida, United States
Emory University/The Emory Clinic
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
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