Clinical trial NCT04419558: Zephyrus II: Efficacy and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
IPF
Idiopathic Interstitial Pneumonia
Interstitial Lung Disease
Lung Fibrosis
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2020-06-05
Enrollment: 372
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: DB Period: Change From Baseline in FVC at Week 48
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: DB Period: Time to Disease Progression
timeFrame: Up to Week 48
measure: DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48
timeFrame: Baseline, Week 48
measure: DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First
timeFrame: Up to Week 48
measure: DB Period: Time to First Acute IPF Exacerbation
timeFrame: Up to Week 48
measure: DB Period: Time to All-Cause Mortality
timeFrame: Up to Week 48
measure: DB Period: Time to First Respiratory Hospitalization
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Lung Health Center
state: Alabama
city: San Francisco
country: United States
facility: UC San Francisco
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Clearwater
country: United States
facility: St. Francis Medical Center
state: Florida
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialists d/b/a PDS Research
state: Florida
city: Tampa
country: United States
facility: TGH/USF Center for Advanced Lung Disease and Lung Transplant
state: Florida
city: Atlanta
country: United States
facility: Emory University/The Emory Clinic
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Boston
country: United States
facility: The General Hospital Corporation d/b/a Massachusetts General Hospital
state: Massachusetts
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: PulmonIx, LLC
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Lung and Critical Care, PA
state: South Carolina
city: Burlington
country: United States
facility: The University of Vermont
state: Vermont
city: Madison
country: United States
facility: University of Wisconsin Clinical Research
state: Wisconsin
city: Ciudad Autonoma De Buenos Aires (CABA)
country: Argentina
facility: Fundacion Respirar - Centro Médico Dra. De Salvo
city: Belo Horizonte
country: Brazil
facility: Hospital das Clínicas da UFMG - Centro de Pesquisas Clínicas do Hospital das Clínicas da Universidade Federal de Minas Gerais - CPC HC/UFMG
state: Minas Gerais
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: HSL-PUCRS Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul
state: Rio Grande Do Sul
city: Blumenau
country: Brazil
facility: Hospital Dia do Pulmão
state: Santa Catarina
city: Botucatu
country: Brazil
facility: Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UPECLIN - UNESP
state: São Paulo
city: Sao Bernardo do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos LTDA EPP
state: São Paulo
city: São Paulo
country: Brazil
facility: CPQuali Pesquisa Clínica Ltda.
city: São Paulo
country: Brazil
facility: Hospital Alemao Oswaldo Cruz
city: São Paulo
country: Brazil
facility: INCOR - Instituto do Coração Centro de Pesquisa Prof. Dr. Fulvio Pileggi Hospital das Clínicas da Faculdade de Medicina da USP - HCFMUSP
city: Beijing
country: China
facility: BeiJing Chao-Yang Hospital,Capital Medical University
city: Beijing
country: China
facility: Beijing Frindship hosiptal capital Medical University
city: Beijing
country: China
facility: China Japan Friendship hospital
city: Beijing
country: China
facility: Peking Union Medical College Hospital
city: Chengdu
country: China
facility: Sichuan People's Hospital
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
city: Hangzhou
country: China
facility: The Second Affiliated Hospital of Zhejiang University School of Medicine
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiaotong University School of Medicine
city: Shanghai
country: China
facility: Shanghai Oriental Hospital
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Tianjing
country: China
facility: General Hospital of Tianjin Medical University
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xian
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
city: Bogota
country: Colombia
facility: Fundación Santa Fe de Bogotá
city: Bogota
country: Colombia
facility: Fundación Neumológica Colombiana
city: Zipaquirá
country: Colombia
facility: Healthy Medical Center S.A.S
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
city: Prague
country: Czechia
facility: Nemocnice Na Bulovce, Klinika pneumologie
city: Aarhus
country: Denmark
facility: Aarhus Universitets Hospital
city: Odense
country: Denmark
facility: Odense University Hospital
city: Santo Domingo
country: Dominican Republic
facility: Centro de Obstetricia y Ginecologia
city: Santo Domingo
country: Dominican Republic
facility: Centro Medico Dominicano
city: Bobigny
country: France
facility: University Hospital Avicenne
city: Bron
country: France
facility: Hôpital Cardio-Vasculaire et Pneumologique Louis Pradel
city: Caen
country: France
facility: CHU de Caen
city: Dijon
country: France
facility: Centre Memoire Ressources Recherche, Hopital F. MITTERRAND
city: Montpellier
country: France
facility: C.H.R.U. de Montpellier - Hôpital Lapeyronie
city: Nice
country: France
facility: CHU de Nice Hôpital Pasteur
city: Paris
country: France
facility: Hôpital Bichat - Claude Bernard
city: Reims
country: France
facility: CHU de Reims Hopital Maison Blanche
city: Rennes
country: France
facility: CHU de Rennes Hôpital Pontchaillou
city: Tours
country: France
facility: Service de Néphrologie, Hôpital Bretonneau, CHRU de Tours
city: Tbilisi
country: Georgia
facility: Research Institute Of Clinical Medicine Todua Clinic
city: Tbilisi
country: Georgia
facility: Clinic Diacor
city: Essen
country: Germany
facility: Ruhrlandklinik-Universitaetsmedizin Essen
city: Gerlingen
country: Germany
facility: Klinik Schillerhoehe
city: Gießen
country: Germany
facility: Agaplesion Evangelisches Krankenhaus Mittelhessen
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Munich
country: Germany
facility: University of Munich
city: Rosenheim
country: Germany
facility: RoMed Klinikum Rosenheim
city: Solingen
country: Germany
facility: Institut fur Pneumologie an der Universitat zu Koln
city: Budapest
country: Hungary
facility: Semmelweis University Clinic of Pulmonology
city: Budapest
country: Hungary
facility: Orszagos Koranyi Tbc es Pulmonologiai Intezet, IV. Tudobelosztaly
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy kh
city: Törökbálint
country: Hungary
facility: Pulmonology Hospital
city: Dublin
country: Ireland
facility: Royal College of Surgeons in Ireland
city: Catania
country: Italy
facility: Gaspare Rodiloco Hospital
city: Forli
country: Italy
facility: Ospedale G.B.Morgagni L.Pierantoni - Azienda Unita Sanitaria Locale (AUSL) di Forli
city: Milan
country: Italy
facility: Ospedale San Giuseppe
city: Modena
country: Italy
facility: AOU Policlinico di Modena
city: Naples
country: Italy
facility: Monaldi Hospital
city: Padova
country: Italy
facility: Azienda Ospedaliera Universitaria di Padova
city: Pavia
country: Italy
facility: IRCCS Fondazione San Matteo di Pavia
city: Rome
country: Italy
facility: Agostina Gemelli University Polyclinic
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese, Policlinico "Le Scotte"
city: Torino
country: Italy
facility: Azienda Ospedaliera Citta' della Salute e delle Scienza di Torino
city: Torrette
country: Italy
facility: Azienda Ospedaliero-Universitaria "Ospedali Riuniti di Ancona"
city: Goyang-si
country: Korea, Republic of
facility: Myongji Hospital
state: Gyeonggi-do
city: Bucheon-si
country: Korea, Republic of
facility: Soonchunhyang University Hospital Bucheon
city: Bucheon
country: Korea, Republic of
facility: The Catholic University of Korea Bucheon St. Mary's Hospital
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Goyang
country: Korea, Republic of
facility: Inje University Hospital Iisan Paik Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Centre
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Hospital Seoul
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Yeouido ST. Mary's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Beirut
country: Lebanon
facility: American University of beirut medical center
city: Beirut
country: Lebanon
facility: Hotel Dieu De France
city: Bir Hassan
country: Lebanon
facility: Rafik Hariri University Hospital (Clinical Research Unit)
city: Mexico
country: Mexico
facility: Instituto Nacional de Enfermedades Respiratorias INER
city: Mexico
country: Mexico
facility: Unidad Medica para la Salud Integral (UMSI)
city: Mexico
country: Mexico
facility: Medical Care and Research S.A. de C.V.
city: Mexico
country: Mexico
facility: St. Lucas Clinical Research Center SA de CV
city: Monterrey
country: Mexico
facility: Centro Regional para el estudio del Adulto Mayor, Servicio de Geriatria, Hospital Universitario Dr Jose Eleuterio Gonzalez
city: Oaxaca
country: Mexico
facility: Oaxaca Site Management Organization S.C. (OSMO)
city: Amsterdam
country: Netherlands
facility: Dept. of Pulmonary Diseases
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Heerlen
country: Netherlands
facility: Longarts - Opleider Longziekten Zuyderland MC
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis BV
city: Nieuwegein
country: Netherlands
facility: Canisius-Wilhelmina Ziekenhuis
city: Lima
country: Peru
facility: Clinica Internacional
city: Lima
country: Peru
facility: Clinica San Pablo
city: Lima
country: Peru
facility: Clinica Providencia
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia / Servicio de Inmunología y Reumatología
city: San Isidro
country: Peru
facility: Centro de Investigacion Ricardo Palma
city: Santa Beatriz
country: Peru
facility: Clinica La luz
city: Bedzin
country: Poland
facility: Centrum Dentystyczno-Lekarskie Promedica Joanna Markiewicz
city: Bialystok
country: Poland
facility: Centrum Medycyny Oddechowej Mroz SJ
city: Katowice
country: Poland
facility: Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slaskiego Uniwersytetu Medycznego w Katowicach
city: Lodz
country: Poland
facility: University Hospital No1
city: Warsaw
country: Poland
facility: Instytut Gruzlicy i Chorob Pluc
city: Belgrade
country: Serbia
facility: Municipal Institute for Lung Diseases and Tuberculosis
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Nis
country: Serbia
facility: University Clinical Center of Nis
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: Barcelona
country: Spain
facility: Hospital Universitario de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitaio de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos-Madrid C/Martin Lagos s/n
city: Madrid
country: Spain
facility: Hospital Universitario Quironsalud Madrid
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Nuestra Senora de Valme
city: Bern
country: Switzerland
facility: Universitätsklinik für Pneumologie
city: Dnipro
country: Ukraine
facility: Communal non-profit enterprise "City clinical hospital #16" of Dnipro Сit Сouncil
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Phthisiology-Pulmonology Center of Ivano-Frankivsk regional council
city: Kyiv
country: Ukraine
facility: National Institute of Phthisiology and Pulmonology named after F. G. Yanovskyi NAMS of Ukraine, Clinical and Functional Department
city: Gillingham
country: United Kingdom
facility: Medway NHS Foundation Trust
state: Kent
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Foundation Trust, Advanced Heart Failure Unit
city: Harlow
country: United Kingdom
facility: The Princess Alexandra Hospital NHS Trust
city: London
country: United Kingdom
facility: Royal Brompton Hospital
city: London
country: United Kingdom
facility: University College London
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References: