Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
- Registration Number
- NCT03955146
- 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 IPF.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 356
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Main Study Cohort: Placebo Placebo Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks in the DB period. Japan Extension Cohort: Placebo Placebo Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks. OLE Period: Placebo/Pamrevlumab Pamrevlumab Participants who receive placebo matching to pamrevlumab in the DB period, will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first. Main Study Cohort: Pamrevlumab Pamrevlumab Participants will receive pamrevlumab 30 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 3 weeks for up to 48 weeks in the DB period. Japan Extension Cohort: Pamrevlumab Pamrevlumab Participants will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks. OLE Period: Pamrevlumab/Pamrevlumab Pamrevlumab Participants who receive pamrevlumab in the DB period will continue to receive the same dose of pamrevlumab for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.
- Primary Outcome Measures
Name Time Method DB Period (Main Study Cohort): 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 could forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were calculated using mixed model for repeated measures (MMRM).
DB Period (Japan Extension Cohort): 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 could forcibly be blown out after full inspiration in the upright position, measured in liters.
- Secondary Outcome Measures
Name Time Method DB Period (Main Study Cohort): Time to Disease Progression Up to Week 48 Time to disease progression was defined as the number of weeks from randomization to either the first occurrence of an absolute ≥10% decline from baseline in percent predicted FVC (FVCpp) or all-cause death, whichever occurred first. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint Up to Week 48 The components of the clinical composite endpoint included acute IPF exacerbation, respiratory hospitalization, or death. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort and Japan Extension Cohort): Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48 Baseline, Week 48 The QLF volume was calculated as QLF = total lung capacity volume multiplied by percentage (%) of quantitative lung fibrosis for fibrosis of the whole lung. LS mean and SE was calculated using MMRM.
DB Period (Main Study Cohort): 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. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): 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. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
DB Period (Main Study Cohort): Time to First Respiratory Hospitalizations Up to Week 48 Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Trial Locations
- Locations (125)
Emory University
🇺🇸Atlanta, Georgia, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
University of Washington
🇺🇸Seattle, Washington, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Texas - Houston
🇺🇸Houston, Texas, United States
University of California San Diego
🇺🇸San Diego, California, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
FSBEI HE First Pavlov Medical University
🇷🇺Saint-Petersburg, Russian Federation
Regional Clinical Hospital #3
🇷🇺Chelyabinsk, Russian Federation
Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare
🇨🇳Taipei, Taiwan
Inje University Busan Paik Hospital
🇰🇷Busan, Korea, Republic of
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Kazan State Medical University based on Republican Clinical Hospital
🇷🇺Kazan, Russian Federation
Clinical Hospital #3
🇷🇺Kemerovo, Russian Federation
Instituto ave Pulmo Fundacion enfisema
🇦🇷Mar del Plata, Buenos Aires, Argentina
Euromedservice, Clinical and Diagnostic Center
🇷🇺Moscow, Russian Federation
Respira Salud Clinica Integral
🇦🇷Godoy Cruz, Provincia De Mendoza, Argentina
Medical Association "NEW HOSPITAL"
🇷🇺Ekaterinburg, Russian Federation
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Ajou University Hospital
🇰🇷Suwon-si, Gyeonggi-do, Korea, Republic of
The Catholic University of Korea, Bucheon St. Mary's Hospital
🇰🇷Bucheon-si, Gyeonggi-do, Korea, Republic of
MONIKI
🇷🇺Moscow, Russian Federation
Vvedenskaya hospital
🇷🇺St. Petersburg, Russian Federation
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Medical Center "Reavita Med SPb"
🇷🇺St. Petersburg, Russian Federation
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
City Clinical Hospital #1 n.a. A.N. Kabanov
🇷🇺Omsk, Russian Federation
Centro Investigacion del Maule CIM
🇨🇱Talca, Region Del Maule, Chile
Instituto Nacional del Torax
🇨🇱Santiago, Region Metropolitana, Chile
Investigaciones en Patologias Respiratorias
🇦🇷San Miguel De Tucumán, Tucumán, Argentina
University of Arizona
🇺🇸Tucson, Arizona, United States
Dartmouth-Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
CIMER
🇨🇱Santiago, Region Metropolitana, Chile
M y F estudios clinicos
🇨🇱Santiago, Region Metropolitana, Chile
University of Alabama at Birmingham Hospital
🇺🇸Birmingham, Alabama, United States
Norton Thoracic Institute
🇺🇸Phoenix, Arizona, United States
Banner University Medical Center - Phoenix
🇺🇸Phoenix, Arizona, United States
Pulmonary Associates, PA - Research
🇺🇸Phoenix, Arizona, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
UT Health San Antonio
🇺🇸San Antonio, Texas, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
General Hospital of Tianjin Medical University
🇨🇳Tianjin, Tianjin, China
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Legacy Research Institute
🇺🇸Portland, Oregon, United States
The Oregon Clinic
🇺🇸Portland, Oregon, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Fundacion Respirar - Centro Médico Dra. De Salvo
🇦🇷Ciudad Autonoma De Buenos Aires (caba), Buenos Aires, Argentina
Centro Medico de Enfermedades Respiratorias
🇦🇷Florida, Buenos Aires, Argentina
Centro Platense en Investigaciones Respiratorias
🇦🇷La Plata, Buenos Aires, Argentina
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
Loma Linda University Health
🇺🇸Loma Linda, California, United States
J&L Research
🇺🇸Conway, Arkansas, United States
David Geffen School of Medicine at UCLA
🇺🇸Los Angeles, California, United States
Medstar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
University of Florida Pulmonary, Critical Care & Sleep Medicine Division
🇺🇸Gainesville, Florida, United States
University of Florida Health, Jacksonville
🇺🇸Jacksonville, Florida, United States
St. Francis Medical Center
🇺🇸Clearwater, Florida, United States
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Pulmonary Disease Specialist, PA d/b/a, PDS Research
🇺🇸Kissimmee, Florida, United States
University of Maryland, Baltimore
🇺🇸Baltimore, Maryland, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Piedmont Healthcare, Inc.
🇺🇸Austell, Georgia, United States
Loyola University of Chicago
🇺🇸Maywood, Illinois, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
The Lung Research Center, LLC
🇺🇸Chesterfield, Missouri, United States
Albany Medical College
🇺🇸Albany, New York, United States
Pulmonary Health Physicians, PC
🇺🇸Liverpool, New York, United States
Pulmonix, LLC
🇺🇸Greensboro, North Carolina, United States
INTEGRIS Baptist Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
Tennessee Comprehensive Lung and Sleep Center
🇺🇸Hendersonville, Tennessee, United States
Baylor Scott and White Research Institute
🇺🇸Dallas, Texas, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Houston Pulmonary Sleep, Allergy and Asthma Associates
🇺🇸Cypress, Texas, United States
The University of Vermont
🇺🇸Burlington, Vermont, United States
Centro de Investigacion Metabolica 'CINME'
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Consultorios Medicos. Organización del Buen Ayre. SRL
🇦🇷Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
INSARES
🇦🇷Ciudad de Mendoza, Mendoza, Argentina
Royal Prince Alfred Hospital
🇦🇺Sydney, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Mater Health Services Adult Hospital
🇦🇺South Brisbane, Queensland, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
BeiJing Chao-Yang Hospital,Capital medical university
🇨🇳Beijing, Beijing, China
China-Japan friendship hospital
🇨🇳Beijing, Beijing, China
Second Affiliated Hospital of Anhui Medical University
🇨🇳Hefei, Anhui, China
Peking Union Medical College Hospital
🇨🇳Beijing, Beijing, China
Nanfang Hospital of Southern Medical University
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Guangzhou Medical University
🇨🇳Guangzhou, Guangdong, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
Henan Provincial chest hospital
🇨🇳Zhengzhou, Henan, China
Shenzhen people's hospital
🇨🇳Shenzhen, Guangdong, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, Hunan, China
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Union Hospital，Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
People's Hospital of Inner Mongolia Autonomous Region
🇨🇳Hohhot, Inner Mongolia, China
Affiliated Hospital of Inner Mongolia Medical University
🇨🇳Hohhot, Inner Mongolia, China
The second hospital of Dalian medical university
🇨🇳Dalian, Liaoning, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The Second Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shanxi, China
Huaxi Hospital of Sichuan University.
🇨🇳ChenDu, Sichuan, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, Ningxia, China
Queen Mary Hospital
🇭🇰Central, Hong Kong
Hangzhou First People's Hospital
🇨🇳Hangzhou, Zhejiang, China
Soonchunhyang University Bucheon Hospital
🇰🇷Bucheon-si, Gyeonggi-do, Korea, Republic of
Tuen Mun Hospital
🇭🇰Hong Kong, Hong Kong
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Centerx
🇰🇷Seoul, Korea, Republic of
UC Davis Medical Center
🇺🇸Sacramento, California, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Lowcountry Lung and Critical Care, PA
🇺🇸Charleston, South Carolina, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States