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

Idiopathic Pulmonary Fibrosis Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04419558
• Other study ID #: FGCL-3019-095
• Status: Terminated
• Phase: Phase 3
• Start date: September 30, 2020
• Est. completion date: September 4, 2023

Study information

• Verified date: October 2023
• Source: FibroGen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 372
• Est. completion date: September 4, 2023
• Est. primary completion date: September 4, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Pamrevlumab
Sterile solution for injection
• Placebo
Sterile solution for injection

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  China,  Colombia,  Czechia,  Denmark,  Dominican Republic,  France,  Georgia,  Germany,  Hungary,  Ireland,  Italy,  Korea, Republic of,  Lebanon,  Mexico,  Netherlands,  Peru,  Poland,  Serbia,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Forced Vital Capacity (FVC) at Week 48		Baseline, Week 48
Secondary	Time to Disease Progression	Defined as absolute FVC percent predicted (FVCpp) decline of =10% or death, whichever occurs first	Up to Week 48
Secondary	Change from Baseline to Week 48 in Quantitative Lung Fibrosis (QLF) Volume		Baseline, Week 48
Secondary	Time to Any Component of the Clinical Composite Endpoint, Whichever Occurs First: Acute IPF Exacerbation, Respiratory Hospitalization, or Death		Up to Week 48
Secondary	Time to First Acute IPF Exacerbation		Up to Week 48
Secondary	Time to All-Cause Mortality		Up to Week 48
Secondary	Time to First Respiratory Hospitalization		Up to Week 48