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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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: NCT03955146
• Other study ID #: FGCL-3019-091
• Status: Terminated
• Phase: Phase 3
• Start date: June 18, 2019
• Est. completion date: August 28, 2023

Study information

• Verified date: March 2024
• 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 IPF.

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 information / eligibility

• Status: Terminated
• Enrollment: 356
• Est. completion date: August 28, 2023
• Est. primary completion date: March 20, 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 (ATS)/European Respiratory Society (ERS)/Japan Radiological Society (JRS)/Latin American Thoracic Association (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 and corrected by hemoglobin (Hb) value =25% and =90% at screening (determined locally).

5. 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 Exclusion Criteria:

1. Previous exposure to pamrevlumab.

2. Evidence of significant obstructive lung disease.

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. History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.

8. 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.

9. Acute IPF exacerbation during screening or randomization.

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 (that is, 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
Pamrevlumab will be administered per dose and schedule specified in the arm description.
• Placebo
Placebo matching to pamrevlumab will be administered per schedule specified in the arm description.

Locations

Country	Name	City	State
Argentina	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	Fundacion Respirar - Centro Médico Dra. De Salvo	Ciudad Autonoma De Buenos Aires (caba)	Buenos Aires
Argentina	INSARES	Ciudad de Mendoza	Mendoza
Argentina	Centro Medico de Enfermedades Respiratorias	Florida	Buenos Aires
Argentina	Respira Salud Clinica Integral	Godoy Cruz	Provincia De Mendoza
Argentina	Centro Platense en Investigaciones Respiratorias	La Plata	Buenos Aires
Argentina	Instituto ave Pulmo Fundacion enfisema	Mar del Plata	Buenos Aires
Argentina	Investigaciones en Patologias Respiratorias	San Miguel De Tucumán	Tucumán
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Mater Health Services Adult Hospital	South Brisbane	Queensland
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Chile	CIMER	Santiago	Region Metropolitana
Chile	Instituto Nacional del Torax	Santiago	Region Metropolitana
Chile	M y F estudios clinicos	Santiago	Region Metropolitana
Chile	Centro Investigacion del Maule CIM	Talca	Region Del Maule
China	BeiJing Chao-Yang Hospital,Capital medical university	Beijing	Beijing
China	China-Japan friendship hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Huaxi Hospital of Sichuan University.	ChenDu	Sichuan
China	The second hospital of Dalian medical university	Dalian	Liaoning
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Hangzhou First People's Hospital	Hangzhou	Zhejiang
China	Second Affiliated Hospital of Anhui Medical University	Hefei	Anhui
China	Affiliated Hospital of Inner Mongolia Medical University	Hohhot	Inner Mongolia
China	People's Hospital of Inner Mongolia Autonomous Region	Hohhot	Inner Mongolia
China	Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning
China	Shenzhen people's hospital	Shenzhen	Guangdong
China	General Hospital of Tianjin Medical University	Tianjin	Tianjin
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	The Second Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shanxi
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia
China	Henan Provincial chest hospital	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan
Hong Kong	Queen Mary Hospital	Central
Hong Kong	Tuen Mun Hospital	Hong Kong
Korea, Republic of	Soonchunhyang University Bucheon Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	The Catholic University of Korea, Bucheon St. Mary's Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Centerx	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyeonggi-do
Russian Federation	Regional Clinical Hospital #3	Chelyabinsk
Russian Federation	Medical Association "NEW HOSPITAL"	Ekaterinburg
Russian Federation	Kazan State Medical University based on Republican Clinical Hospital	Kazan
Russian Federation	Clinical Hospital #3	Kemerovo
Russian Federation	Euromedservice, Clinical and Diagnostic Center	Moscow
Russian Federation	MONIKI	Moscow
Russian Federation	City Clinical Hospital #1 n.a. A.N. Kabanov	Omsk
Russian Federation	FSBEI HE First Pavlov Medical University	Saint-Petersburg
Russian Federation	Medical Center "Reavita Med SPb"	St. Petersburg
Russian Federation	Vvedenskaya hospital	St. Petersburg
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare	Taipei
United States	Albany Medical College	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University	Atlanta	Georgia
United States	University of Colorado Denver	Aurora	Colorado
United States	Piedmont Healthcare, Inc.	Austell	Georgia
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	University of Alabama at Birmingham Hospital	Birmingham	Alabama
United States	The University of Vermont	Burlington	Vermont
United States	Lowcountry Lung and Critical Care, PA	Charleston	South Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	The Lung Research Center, LLC	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	University of Cincinnati	Cincinnati	Ohio
United States	St. Francis Medical Center	Clearwater	Florida
United States	Ohio State University	Columbus	Ohio
United States	J&L Research	Conway	Arkansas
United States	Houston Pulmonary Sleep, Allergy and Asthma Associates	Cypress	Texas
United States	Baylor Scott and White Research Institute	Dallas	Texas
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	University of Florida Pulmonary, Critical Care & Sleep Medicine Division	Gainesville	Florida
United States	Spectrum Health	Grand Rapids	Michigan
United States	Pulmonix, LLC	Greensboro	North Carolina
United States	Tennessee Comprehensive Lung and Sleep Center	Hendersonville	Tennessee
United States	Penn State Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	University of Texas - Houston	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Florida Health, Jacksonville	Jacksonville	Florida
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Pulmonary Disease Specialist, PA d/b/a, PDS Research	Kissimmee	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Pulmonary Health Physicians, PC	Liverpool	New York
United States	Loma Linda University Health	Loma Linda	California
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	Loyola University of Chicago	Maywood	Illinois
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	INTEGRIS Baptist Medical Center	Oklahoma City	Oklahoma
United States	Temple University	Philadelphia	Pennsylvania
United States	Banner University Medical Center - Phoenix	Phoenix	Arizona
United States	Norton Thoracic Institute	Phoenix	Arizona
United States	Pulmonary Associates, PA - Research	Phoenix	Arizona
United States	Legacy Research Institute	Portland	Oregon
United States	The Oregon Clinic	Portland	Oregon
United States	Rhode Island Hospital	Providence	Rhode Island
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Health	Salt Lake City	Utah
United States	UT Health San Antonio	San Antonio	Texas
United States	University of California San Diego	San Diego	California
United States	University of Washington	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California
United States	University of South Florida	Tampa	Florida
United States	Renovatio Clinical	The Woodlands	Texas
United States	University of Arizona	Tucson	Arizona
United States	Medstar Georgetown University Hospital	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Chile,  China,  Hong Kong,  Korea, Republic of,  Russian Federation,  Taiwan, 

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	Time to disease progression was defined as absolute percent predicted FVC (FVCpp) decline of =10% or death, whichever occurs first.	Baseline to Week 48
Secondary	Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48		Baseline, Week 48
Secondary	Time to Any Component of the Clinical Composite Endpoint, Whichever Occurs First: Acute IPF Exacerbation, Respiratory Hospitalization, or Death		Baseline to Week 48
Secondary	Time to First Acute IPF Exacerbation During Study		Baseline to Week 48
Secondary	Time to All-cause Mortality During Study		Baseline to Week 48
Secondary	Time to First Respiratory Hospitalizations During Study		Baseline to Week 48