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

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

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.

Study Overview

• Status: Terminated
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Pamrevlumab; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 372
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma De Buenos Aires (CABA), Argentina
    • Fundacion Respirar - Centro Medico Dra. De Salvo
• Brazil
  • São Paulo, Brazil, 01323-001
    • Hospital Alemao Oswaldo Cruz
  • São Paulo, Brazil, 01228-000
    • CPQuali Pesquisa Clinica Ltda.
  • São Paulo, Brazil, 05403-000
    • INCOR - Instituto do Coração Centro de Pesquisa Prof. Dr. Fulvio Pileggi Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30130-100
      • Hospital das Clínicas da UFMG - Centro de Pesquisas Clínicas do Hospital das Clínicas da Universidade Federal de Minas Gerais - CPC HC/UFMG
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90020-090
      • Irmandade da Santa Casa de Misericordia de Porto Alegre
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
      • HSL-PUCRS Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89030-101
      • Hospital Dia do Pulmao
  • São Paulo
    • Botucatu, São Paulo, Brazil, 18618-686
      • Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UPECLIN - UNESP
    • Sao Bernardo do Campo, São Paulo, Brazil, 09715-090
      • CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA EPP
• China
  • Beijing, China
    • Peking Union Medical College Hospital
  • Beijing, China
    • China Japan Friendship Hospital
  • Beijing, China
    • Beijing Chao-Yang Hospital,Capital Medical University
  • Beijing, China
    • Beijing Frindship hosiptal capital Medical University
  • Chengdu, China
    • Sichuan People's Hospital
  • Guangzhou, China
    • Guangdong Provincial People's Hospital
  • Hangzhou, China
    • The Second Affiliated Hospital of Zhejiang University School of Medicine
  • Shanghai, China
    • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
  • Shanghai, China
    • Shanghai Oriental Hospital
  • Shenyang, China
    • The First Hospital of China Medical University
  • Tianjing, China
    • General Hospital of Tianjin Medical University
  • Wuhan, China
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Wuhan, China
    • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology
  • Xian, China
    • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Yinchuan, China
    • General Hospital of Ningxia Medical University
• Colombia
  • Bogota, Colombia, 110121
    • Fundacion Santa Fe de Bogota
  • Bogota, Colombia, 110131
    • Fundación Neumologica Colombiana
  • Zipaquirá, Colombia, 250252
    • Healthy Medical Center S.A.S
• Czechia
  • Brno, Czechia, 625 00
    • Fakultni nemocnice Brno
  • Jihlava, Czechia, 586 33
    • Nemocnice Jihlava
  • Prague, Czechia, 18081
    • Nemocnice Na Bulovce, Klinika pneumologie
• Denmark
  • Aarhus, Denmark, DK-8200
    • Aarhus Universitets Hospital
  • Odense, Denmark, 5000
    • Odense University Hospital
• Dominican Republic
  • Santo Domingo, Dominican Republic, 10205
    • Centro de Obstetricia y Ginecologia
  • Santo Domingo, Dominican Republic, 456
    • Centro Medico Dominicano
• France
  • Bobigny, France, 93000
    • University Hospital Avicenne
  • Bron, France, 69677
    • Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
  • Caen, France, 14033
    • CHU de Caen
  • Dijon, France, 21079
    • Centre Memoire Ressources Recherche, Hopital F. MITTERRAND
  • Montpellier, France, 34295
    • C.H.R.U. de Montpellier - Hôpital Lapeyronie
  • Nice, France, 06000
    • CHU de Nice Hopital Pasteur
  • Paris, France, 75018
    • Hôpital Bichat - Claude Bernard
  • Reims, France, 51092
    • CHU de Reims Hopital Maison Blanche
  • Rennes, France, 35033
    • CHU de Rennes Hôpital Pontchaillou
  • Tours, France, 37044
    • Service de Néphrologie, Hôpital Bretonneau, CHRU de Tours
• Georgia
  • Tbilisi, Georgia, 0112
    • Research Institute Of Clinical Medicine Todua Clinic
  • Tbilisi, Georgia, 0159
    • Clinic Diacor
• Germany
  • Essen, Germany, 45239
    • Ruhrlandklinik-Universitaetsmedizin Essen
  • Gerlingen, Germany, 70839
    • Klinik Schillerhoehe
  • Gießen, Germany, 035398
    • Agaplesion Evangelisches Krankenhaus Mittelhessen
  • Hamburg, Germany, 20246
    • Universitätsklinikum Hamburg-Eppendorf
  • Munich, Germany, 81377
    • University of Munich
  • Rosenheim, Germany, 83022
    • RoMed Klinikum Rosenheim
  • Solingen, Germany, 83022
    • Institut fur Pneumologie an der Universitat zu Koln
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis University Clinic of Pulmonology
  • Budapest, Hungary, 1121
    • Orszagos Koranyi Tbc es Pulmonologiai Intezet, IV. Tudobelosztaly
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy kh
  • Törökbálint, Hungary, 2045
    • Pulmonology Hospital
• Ireland
  • Dublin, Ireland, D09YD60
    • Royal College of Surgeons in Ireland
• Italy
  • Catania, Italy, 95123
    • Gaspare Rodiloco Hospital
  • Forli, Italy, 47121
    • Ospedale G.B.Morgagni L.Pierantoni - Azienda Unita Sanitaria Locale (AUSL) di Forli
  • Milan, Italy, 20123
    • Ospedale San Giuseppe
  • Modena, Italy, 41124
    • AOU Policlinico di Modena
  • Naples, Italy, 80131
    • Monaldi Hospital
  • Padova, Italy, 35128
    • Azienda Ospedaliera Universitaria Di Padova
  • Pavia, Italy, 27100
    • IRCCS Fondazione San Matteo di Pavia
  • Rome, Italy, 00168
    • Agostina Gemelli University Polyclinic
  • Siena, Italy, 53100
    • Azienda Ospedaliera Universitaria Senese, Policlinico "Le Scotte"
  • Torino, Italy, 0126
    • Azienda Ospedaliera Citta' della Salute e delle Scienza di Torino
  • Torrette, Italy, 60126
    • Azienda Ospedaliero-Universitaria "Ospedali Riuniti di Ancona"
• Korea, Republic of
  • Bucheon, Korea, Republic of, 14647
    • The Catholic University of Korea Bucheon St. Mary's Hospital
  • Bucheon-si, Korea, Republic of, 14584
    • Soonchunhyang University Hospital Bucheon
  • Busan, Korea, Republic of, 48108
    • Inje University Haeundae Paik Hospital
  • Goyang, Korea, Republic of, 10380
    • Inje University Hospital Iisan Paik Hospital
  • Gwangju, Korea, Republic of, 61469
    • Chonnam National University Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Centre
  • Seongnam, Korea, Republic of, 13620
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 3722
    • Severance Hospital
  • Seoul, Korea, Republic of, 17104
    • KyungHee University Medical Center
  • Seoul, Korea, Republic of, 4401
    • Soonchunhyang University Hospital Seoul
  • Seoul, Korea, Republic of, 7345
    • The Catholic University of Korea, Yeouido St. Mary's Hospital
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10475
      • Myongji Hospital
• Lebanon
  • Beirut, Lebanon
    • American University of Beirut Medical Center
  • Beirut, Lebanon
    • Hotel Dieu de France
  • Bir Hassan, Lebanon
    • Rafik Hariri University Hospital (Clinical Research Unit)
• Mexico
  • Mexico, Mexico, 14080
    • Instituto Nacional de Enfermedades Respiratorias INER
  • Mexico, Mexico, 66465
    • Unidad Medica para la Salud Integral (UMSI)
  • Mexico, Mexico, 97070
    • Medical Care and Research S.A. de C.V.
  • Mexico, Mexico, CP97217
    • St. Lucas Clinical Research Center SA de CV
  • Monterrey, Mexico, 64460
    • Centro Regional para el estudio del Adulto Mayor, Servicio de Geriatria, Hospital Universitario Dr Jose Eleuterio Gonzalez
  • Oaxaca, Mexico, 68000
    • Oaxaca Site Management Organization S.C. (OSMO)
• Netherlands
  • Amsterdam, Netherlands, 30.033
    • Dept. of Pulmonary Diseases
  • Eindhoven, Netherlands, 5623 EJ
    • Catharina Hospital
  • Heerlen, Netherlands, 6419
    • Longarts - Opleider Longziekten Zuyderland MC
  • Nieuwegein, Netherlands, 3435
    • St. Antonius Ziekenhuis BV
  • Nieuwegein, Netherlands, 6533
    • Canisius-Wilhelmina Ziekenhuis
• Peru
  • Lima, Peru, 15001
    • Clinica Internacional
  • Lima, Peru, 150140
    • Clinica San Pablo
  • Lima, Peru, 15088
    • Clinica Providencia
  • Lima, Peru, 15102
    • Hospital Nacional Cayetano Heredia / Servicio de Inmunología y Reumatología
  • San Isidro, Peru, 150131
    • Centro de Investigación Ricardo Palma
  • Santa Beatriz, Peru, 15046
    • Clinica La Luz
• Poland
  • Bedzin, Poland, 42-500
    • Centrum Dentystyczno-Lekarskie PROMEDICA Joanna Markiewicz
  • Bialystok, Poland, 15-044
    • Centrum Medycyny Oddechowej Mroz SJ
  • Katowice, Poland, 40-635
    • Górnoslaskie Centrum Medyczne im. prof. Leszka Gieca Slaskiego Uniwersytetu Medycznego w Katowicach
  • Lodz, Poland, 90-153
    • University Hospital No1
  • Warsaw, Poland, 01-138
    • Instytut Gruzlicy i Chorob Pluc
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia
  • Belgrade, Serbia, 11000
    • Municipal Institute for lung diseases and tuberculosis
  • Nis, Serbia, 18000
    • University Clinical Center of Nis
  • Sremska Kamenica, Serbia, 21204
    • Institute for pulmonary diseases of Vojvodina
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitario de Bellvitge
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 28223
    • Hospital Universitario Quironsalud Madrid
  • Madrid, Spain, 28006
    • Hospital Universitaio de La Princesa
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos-Madrid C/Martin Lagos s/n
  • Santander, Spain, 39008
    • Hospital Universitario Marques de Valdecilla
  • Sevilla, Spain, 41014
    • Hospital Universitario Nuestra Señora de Valme
• Switzerland
  • Bern, Switzerland, 3010
    • Universitätsklinik für Pneumologie
• Ukraine
  • Dnipro, Ukraine, 49069
    • Communal non-profit enterprise "City clinical hospital #16" of Dnipro Сit Сouncil
  • Ivano-Frankivsk, Ukraine, 76018
    • Ivano-Frankivsk Regional Phthisiology-Pulmonology Center of Ivano-Frankivsk regional council
  • Kyiv, Ukraine, 03680
    • National Institute of Phthisiology and Pulmonology named after F. G. Yanovskyi NAMS of Ukraine, Clinical and Functional Department
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 0AY
    • Papworth Hospital NHS Foundation Trust, Advanced Heart Failure Unit
  • Harlow, United Kingdom, CM20 1QX
    • The Princess Alexandra Hospital NHS Trust
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital
  • London, United Kingdom, WC1E 6JF
    • University College London
  • Manchester, United Kingdom, M23 9LT
    • Manchester University NHS Foundation Trust
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Kent
    • Gillingham, Kent, United Kingdom, ME7 5NY
      • Medway NHS Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB Lung Health Center
  • California
    • San Francisco, California, United States, 94143
      • UC San Francisco
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Center
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialists d/b/a PDS Research
    • Tampa, Florida, United States, 33606
      • TGH/USF Center for Advanced Lung Disease and Lung Transplant
  • Georgia
    • Atlanta, Georgia, United States, 30324
      • Emory University/The Emory Clinic
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • The General Hospital Corporation d/b/a Massachusetts General Hospital
  • Michigan
    • Grand Rapids, Michigan, United States, 49504
      • Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greensboro, North Carolina, United States, 27403
      • Pulmonix, LLC
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Ohio State University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Lung and Critical Care, PA
  • Vermont
    • Burlington, Vermont, United States, 05405
      • The University of Vermont
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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.
2. High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
3. FVCpp value >45% and <95% at Screening and Day 1 (prior to randomization).
4. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90%.
5. 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:

1. Previous exposure to pamrevlumab.
2. Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
3. Female participants who are pregnant or nursing.
4. Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study.
5. Interstitial lung disease other than IPF.
6. Sustained improvement in the severity of IPF during the 12 months prior to screening.
7. 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.
8. 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).
9. Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening.
10. 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.
11. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Pamrevlumab; Sterile solution for injection; Other Names: FG-3019
Experimental: Placebo; Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks	Drug: Placebo; Sterile solution for injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Change From Baseline in FVC at 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).	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB Period: Time to Disease Progression	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.	Up to Week 48
DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at 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.	Baseline, Week 48
DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First	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.	Up to Week 48
DB Period: Time to First Acute IPF Exacerbation	'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.	Up to Week 48
DB Period: Time to All-Cause Mortality	'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.	Up to Week 48
DB Period: Time to First Respiratory Hospitalization	'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.	Up to Week 48

Collaborators and Investigators

• Sponsor: FibroGen

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2020
• Primary Completion (Actual): September 4, 2023
• Study Completion (Actual): September 4, 2023

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 3, 2020
• First Posted (Actual): June 5, 2020

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 8, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; IPF; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Lung Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: FGCL-3019-095

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No