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)
Longarts - Opleider Longziekten Zuyderland MC
🇳🇱Heerlen, Netherlands
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University College London
🇬🇧London, United Kingdom
The Princess Alexandra Hospital NHS Trust
🇬🇧Harlow, United Kingdom
Rafik Hariri University Hospital (Clinical Research Unit)
🇱🇧Bir Hassan, Lebanon
UAB Lung Health Center
🇺🇸Birmingham, Alabama, United States
Soonchunhyang University Hospital Bucheon
🇰🇷Bucheon-si, Korea, Republic of
The Catholic University of Korea Bucheon St. Mary's Hospital
🇰🇷Bucheon, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
St. Francis Medical Center
🇺🇸Clearwater, Florida, United States
UC San Francisco
🇺🇸San Francisco, California, 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
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Spectrum Health
🇺🇸Grand Rapids, Michigan, United States
The General Hospital Corporation d/b/a Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
PulmonIx, LLC
🇺🇸Greensboro, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Low Country Lung and Critical Care, PA
🇺🇸Charleston, South Carolina, United States
The University of Vermont
🇺🇸Burlington, Vermont, United States
University of Wisconsin Clinical Research
🇺🇸Madison, Wisconsin, United States
Fundacion Respirar - Centro Médico Dra. De Salvo
🇦🇷Ciudad Autonoma De Buenos Aires (CABA), Argentina
Irmandade da Santa Casa de Misericórdia de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
HSL-PUCRS Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital Dia do Pulmão
🇧🇷Blumenau, Santa Catarina, Brazil
Peking Union Medical College Hospital
🇨🇳Beijing, China
CPQuali Pesquisa Clínica Ltda.
🇧🇷São Paulo, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷São Paulo, Brazil
China Japan Friendship hospital
🇨🇳Beijing, China
Sichuan People's Hospital
🇨🇳Chengdu, China
BeiJing Chao-Yang Hospital,Capital Medical University
🇨🇳Beijing, China
Beijing Frindship hosiptal capital Medical University
🇨🇳Beijing, China
Shanghai Oriental Hospital
🇨🇳Shanghai, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, China
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, China
The First Hospital of China Medical University
🇨🇳Shenyang, China
General Hospital of Tianjin Medical University
🇨🇳Tianjing, China
Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
General Hospital of Ningxia Medical University
🇨🇳Yinchuan, China
Fundación Santa Fe de Bogotá
🇨🇴Bogota, Colombia
Nemocnice Na Bulovce, Klinika pneumologie
🇨🇿Prague, Czechia
Fakultní nemocnice Brno
🇨🇿Brno, Czechia
Nemocnice Jihlava
🇨🇿Jihlava, Czechia
Aarhus Universitets Hospital
🇩🇰Aarhus, Denmark
Odense University Hospital
🇩🇰Odense, Denmark
University Hospital Avicenne
🇫🇷Bobigny, France
Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
🇫🇷Bron, France
CHU de Caen
🇫🇷Caen, France
C.H.R.U. de Montpellier - Hôpital Lapeyronie
🇫🇷Montpellier, France
Centre Memoire Ressources Recherche, Hopital F. MITTERRAND
🇫🇷Dijon, France
Hôpital Bichat - Claude Bernard
🇫🇷Paris, France
CHU de Nice Hôpital Pasteur
🇫🇷Nice, France
CHU de Reims Hopital Maison Blanche
🇫🇷Reims, France
Service de Néphrologie, Hôpital Bretonneau, CHRU de Tours
🇫🇷Tours, France
Research Institute Of Clinical Medicine Todua Clinic
🇬🇪Tbilisi, Georgia
Ruhrlandklinik-Universitaetsmedizin Essen
🇩🇪Essen, Germany
University of Munich
🇩🇪Munich, Germany
Institut fur Pneumologie an der Universitat zu Koln
🇩🇪Solingen, Germany
RoMed Klinikum Rosenheim
🇩🇪Rosenheim, Germany
Fejer Megyei Szent Gyorgy kh
🇭🇺Szekesfehervar, Hungary
Universitätsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Orszagos Koranyi Tbc es Pulmonologiai Intezet, IV. Tudobelosztaly
🇭🇺Budapest, Hungary
Royal College of Surgeons in Ireland
🇮🇪Dublin, Ireland
Gaspare Rodiloco Hospital
🇮🇹Catania, Italy
Ospedale G.B.Morgagni L.Pierantoni - Azienda Unita Sanitaria Locale (AUSL) di Forli
🇮🇹Forli, Italy
AOU Policlinico di Modena
🇮🇹Modena, Italy
Ospedale San Giuseppe
🇮🇹Milan, Italy
Monaldi Hospital
🇮🇹Naples, Italy
Azienda Ospedaliera Universitaria di Padova
🇮🇹Padova, Italy
IRCCS Fondazione San Matteo di Pavia
🇮🇹Pavia, Italy
Agostina Gemelli University Polyclinic
🇮🇹Rome, Italy
Azienda Ospedaliera Citta' della Salute e delle Scienza di Torino
🇮🇹Torino, Italy
Azienda Ospedaliero-Universitaria "Ospedali Riuniti di Ancona"
🇮🇹Torrette, Italy
Azienda Ospedaliera Universitaria Senese, Policlinico "Le Scotte"
🇮🇹Siena, Italy
Myongji Hospital
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Inje University Hospital Iisan Paik Hospital
🇰🇷Goyang, Korea, Republic of
Gachon University Gil Medical Centre
🇰🇷Incheon, Korea, Republic of
Severance hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Kyunghee University Medical Center
🇰🇷Seoul, Korea, Republic of
Soonchunhyang University Hospital Seoul
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Yeouido ST. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
American University of beirut medical center
🇱🇧Beirut, Lebanon
Instituto Nacional de Enfermedades Respiratorias INER
🇲🇽Mexico, Mexico
Unidad Medica para la Salud Integral (UMSI)
🇲🇽Mexico, Mexico
Hotel Dieu De France
🇱🇧Beirut, Lebanon
Dept. of Pulmonary Diseases
🇳🇱Amsterdam, Netherlands
Centro Regional para el estudio del Adulto Mayor, Servicio de Geriatria, Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Mexico
Medical Care and Research S.A. de C.V.
🇲🇽Mexico, Mexico
St. Antonius Ziekenhuis BV
🇳🇱Nieuwegein, Netherlands
Clinica Providencia
🇵🇪Lima, Peru
Canisius-Wilhelmina Ziekenhuis
🇳🇱Nieuwegein, Netherlands
University Hospital No1
🇵🇱Lodz, Poland
Centro de Investigacion Ricardo Palma
🇵🇪San Isidro, Peru
Centrum Dentystyczno-Lekarskie Promedica Joanna Markiewicz
🇵🇱Bedzin, Poland
Clinica La luz
🇵🇪Santa Beatriz, Peru
Instytut Gruzlicy i Chorob Pluc
🇵🇱Warsaw, Poland
Centrum Medycyny Oddechowej Mroz SJ
🇵🇱Bialystok, Poland
Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slaskiego Uniwersytetu Medycznego w Katowicach
🇵🇱Katowice, Poland
University Clinical Center of Serbia
🇷🇸Belgrade, Serbia
Municipal Institute for Lung Diseases and Tuberculosis
🇷🇸Belgrade, Serbia
University Clinical Center of Nis
🇷🇸Nis, Serbia
Hospital Universitario de Bellvitge
🇪🇸Barcelona, Spain
Hospital Universitaio de La Princesa
🇪🇸Madrid, Spain
Hospital Clinico San Carlos-Madrid C/Martin Lagos s/n
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Hospital Universitario Quironsalud Madrid
🇪🇸Madrid, Spain
Universitätsklinik für Pneumologie
🇨🇭Bern, Switzerland
Ivano-Frankivsk Regional Phthisiology-Pulmonology Center of Ivano-Frankivsk regional council
🇺🇦Ivano-Frankivsk, Ukraine
Hospital Universitario Nuestra Senora de Valme
🇪🇸Sevilla, Spain
Medway NHS Foundation Trust
🇬🇧Gillingham, Kent, United Kingdom
Communal non-profit enterprise "City clinical hospital #16" of Dnipro Сit Сouncil
🇺🇦Dnipro, Ukraine
National Institute of Phthisiology and Pulmonology named after F. G. Yanovskyi NAMS of Ukraine, Clinical and Functional Department
🇺🇦Kyiv, Ukraine
Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Papworth Hospital NHS Foundation Trust, Advanced Heart Failure Unit
🇬🇧Cambridge, United Kingdom
Manchester University NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Southampton General Hospital
🇬🇧Southampton, United Kingdom
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Klinik Schillerhoehe
🇩🇪Gerlingen, Germany
National Jewish Health
🇺🇸Denver, Colorado, United States
Semmelweis University Clinic of Pulmonology
🇭🇺Budapest, Hungary
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
The University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Pulmonary Disease Specialists d/b/a PDS Research
🇺🇸Kissimmee, Florida, United States
Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UPECLIN - UNESP
🇧🇷Botucatu, São Paulo, Brazil
INCOR - Instituto do Coração Centro de Pesquisa Prof. Dr. Fulvio Pileggi Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP
🇧🇷São Paulo, Brazil
Yale University
🇺🇸New Haven, Connecticut, United States
Penn State Milton S Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
🇨🇳Shanghai, China
The Second Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xian, China
Centro de Obstetricia y Ginecologia
🇩🇴Santo Domingo, Dominican Republic
CHU de Rennes Hôpital Pontchaillou
🇫🇷Rennes, France
Agaplesion Evangelisches Krankenhaus Mittelhessen
🇩🇪Gießen, Germany
Pulmonology Hospital
🇭🇺Törökbálint, Hungary
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Oaxaca Site Management Organization S.C. (OSMO)
🇲🇽Oaxaca, Mexico
Catharina Hospital
🇳🇱Eindhoven, Netherlands
Fundación Neumológica Colombiana
🇨🇴Bogota, Colombia
Healthy Medical Center S.A.S
🇨🇴Zipaquirá, Colombia
Centro Medico Dominicano
🇩🇴Santo Domingo, Dominican Republic
St. Lucas Clinical Research Center SA de CV
🇲🇽Mexico, Mexico
Clinica Internacional
🇵🇪Lima, Peru
CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA EPP
🇧🇷Sao Bernardo do Campo, São Paulo, Brazil
Hospital Nacional Cayetano Heredia / Servicio de Inmunología y Reumatología
🇵🇪Lima, Peru
Clinic Diacor
🇬🇪Tbilisi, Georgia
Institute for Pulmonary Diseases of Vojvodina
🇷🇸Sremska Kamenica, Serbia
Clinica San Pablo
🇵🇪Lima, Peru
Hospital das Clínicas da UFMG - Centro de Pesquisas Clínicas do Hospital das Clínicas da Universidade Federal de Minas Gerais - CPC HC/UFMG
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Royal Brompton Hospital
🇬🇧London, United Kingdom