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

NCT03955146 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: FGCL-3019-091
• Study Type: interventional
• Target: 393
• Locations: 9 countries
• Sites: 125

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 IPF.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Lung Fibrosis

Outcome Measures

Primary Outcomes (2)

• DB Period (Main Study Cohort): 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 could forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were calculated using mixed model for repeated measures (MMRM).

  Baseline, Week 48

• DB Period (Japan Extension Cohort): 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 could forcibly be blown out after full inspiration in the upright position, measured in liters.

  Baseline, Week 48

Secondary Outcomes (6)

• DB Period (Main Study Cohort): Time to Disease Progression

  Up to Week 48

• DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint

  Up to Week 48

• DB Period (Main Study Cohort and Japan Extension Cohort): Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48

  Baseline, Week 48

• DB Period (Main Study Cohort): Time to First Acute IPF Exacerbation

  Up to Week 48

• DB Period (Main Study Cohort): Time to All-Cause Mortality

  Up to Week 48

Study Arms (6)

Main Study Cohort: Pamrevlumab

EXPERIMENTAL

Participants will receive pamrevlumab 30 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 3 weeks for up to 48 weeks in the DB period.

Drug: Pamrevlumab

Main Study Cohort: Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks in the DB period.

Drug: Placebo

Japan Extension Cohort: Pamrevlumab

EXPERIMENTAL

Participants will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks.

Drug: Pamrevlumab

Japan Extension Cohort: Placebo

PLACEBO COMPARATOR

Participants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks.

Drug: Placebo

OLE Period: Pamrevlumab/Pamrevlumab

EXPERIMENTAL

Participants who receive pamrevlumab in the DB period will continue to receive the same dose of pamrevlumab for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.

Drug: Pamrevlumab

OLE Period: Placebo/Pamrevlumab

EXPERIMENTAL

Participants who receive placebo matching to pamrevlumab in the DB period, will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks in the OLE period or until pamrevlumab is commercially available for the indication of IPF, or the sponsor decides to end the OLE period, whichever occurrs first.

Drug: Pamrevlumab

Interventions

Pamrevlumab DRUG

Pamrevlumab will be administered per dose and schedule specified in the arm description.

Also known as: FG-3019

Japan Extension Cohort: Pamrevlumab; Main Study Cohort: Pamrevlumab; OLE Period: Pamrevlumab/Pamrevlumab; OLE Period: Placebo/Pamrevlumab

Placebo DRUG

Placebo matching to pamrevlumab will be administered per schedule specified in the arm description.

Japan Extension Cohort: Placebo; Main Study Cohort: Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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 and corrected by hemoglobin (Hb) value ≥25% and ≤90% at screening (determined locally).
• 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.

You may not qualify if:

• Previous exposure to pamrevlumab.
• Evidence of significant obstructive lung disease.
• 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.
• History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
• 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.
• Acute IPF exacerbation during screening or randomization.
• 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.
• History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.

Sponsors & Collaborators

• Kyntra Bio: lead

Study Sites (125)

University of Alabama at Birmingham Hospital

Birmingham, Alabama, 35294, United States

Location

Banner University Medical Center - Phoenix

Phoenix, Arizona, 85006, United States

Location

Norton Thoracic Institute

Phoenix, Arizona, 85013, United States

Location

Pulmonary Associates, PA - Research

Phoenix, Arizona, 85032, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

J&L Research

Conway, Arkansas, 72032, United States

Location

Loma Linda University Health

Loma Linda, California, 92354, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

University of California San Diego

San Diego, California, 92103, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

National Jewish Health

Denver, Colorado, 80207, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06510, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

St. Francis Medical Center

Clearwater, Florida, 33765, United States

Location

University of Florida Pulmonary, Critical Care & Sleep Medicine Division

Gainesville, Florida, 32610, United States

Location

University of Florida Health, Jacksonville

Jacksonville, Florida, 32209, United States

Location

Mayo Clinic

Jacksonville, Florida, 32224, United States

Location

Pulmonary Disease Specialist, PA d/b/a, PDS Research

Kissimmee, Florida, 34741, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Piedmont Healthcare, Inc.

Austell, Georgia, 30106, United States

Location

Northwestern University

Chicago, Illinois, 60612, United States

Location

Loyola University of Chicago

Maywood, Illinois, 60153, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49546, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

The Lung Research Center, LLC

Chesterfield, Missouri, 63017, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Albany Medical College

Albany, New York, 12208, United States

Location

Pulmonary Health Physicians, PC

Liverpool, New York, 13088, United States

Location

Pulmonix, LLC

Greensboro, North Carolina, 27403, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

INTEGRIS Baptist Medical Center

Oklahoma City, Oklahoma, 73112, United States

Location

Legacy Research Institute

Portland, Oregon, 97210, United States

Location

The Oregon Clinic

Portland, Oregon, 97220, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Lowcountry Lung and Critical Care, PA

Charleston, South Carolina, 29406, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Tennessee Comprehensive Lung and Sleep Center

Hendersonville, Tennessee, 37075, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37204, United States

Location

Houston Pulmonary Sleep, Allergy and Asthma Associates

Cypress, Texas, 77429, United States

Location

Baylor Scott and White Research Institute

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Texas - Houston

Houston, Texas, 77030, United States

Location

UT Health San Antonio

San Antonio, Texas, 78229, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

The University of Vermont

Burlington, Vermont, 05405, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Fundacion Respirar - Centro Médico Dra. De Salvo

Ciudad Autonoma de Buenos Aires (caba), Buenos Aires, 1426, Argentina

Location

Centro de Investigacion Metabolica 'CINME'

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1027AAP, Argentina

Location

Consultorios Medicos. Organización del Buen Ayre. SRL

Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425FVH, Argentina

Location

Centro Medico de Enfermedades Respiratorias

Florida, Buenos Aires, B1602DQD, Argentina

Location

Centro Platense en Investigaciones Respiratorias

La Plata, Buenos Aires, 1900, Argentina

Location

Instituto ave Pulmo Fundacion enfisema

Mar del Plata, Buenos Aires, B7602DCK, Argentina

Location

Respira Salud Clinica Integral

Godoy Cruz, Mendoza Province, M5501GCA, Argentina

Location

INSARES

Mendoza, Mendoza Province, M5500CCG, Argentina

Location

Investigaciones en Patologias Respiratorias

San Miguel de Tucumán, Tucumán Province, T4000IAR, Argentina

Location

Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Mater Health Services Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Centro Investigacion del Maule CIM

Talca, Maule Region, 3465586, Chile

Location

Instituto Nacional del Torax

Santiago, Santiago Metropolitan, 7500691, Chile

Location

CIMER

Santiago, Santiago Metropolitan, 7500692, Chile

Location

M y F estudios clinicos

Santiago, Santiago Metropolitan, 7750495, Chile

Location

Second Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230000, China

Location

BeiJing Chao-Yang Hospital,Capital medical university

Beijing, Beijing Municipality, 100020, China

Location

China-Japan friendship hospital

Beijing, Beijing Municipality, 100029, China

Location

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510000, China

Location

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

Location

Shenzhen people's hospital

Shenzhen, Guangdong, 518020, China

Location

Henan Provincial People's Hospital

Zhengzhou, Henan, 450000, China

Location

Henan Provincial chest hospital

Zhengzhou, Henan, 450003, China

Location

Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Union Hospital，Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

The Second Xiangya Hospital of Central South University

Changsha, Hunan, 410011, China

Location

Affiliated Hospital of Inner Mongolia Medical University

Hohhot, Inner Mongolia, 10010, China

Location

People's Hospital of Inner Mongolia Autonomous Region

Hohhot, Inner Mongolia, 10020, China

Location

The second hospital of Dalian medical university

Dalian, Liaoning, 116001, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

General Hospital of Ningxia Medical University

Yinchuan, Ningxia, 750004, China

Location

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi’an, Shanxi, 710004, China

Location

Huaxi Hospital of Sichuan University.

Chengdu, Sichuan, 6100141, China

Location

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300052, China

Location

Hangzhou First People's Hospital

Hangzhou, Zhejiang, 310006, China

Location

Queen Mary Hospital

Central, Hong Kong

Location

Tuen Mun Hospital

Hong Kong, Hong Kong

Location

Regional Clinical Hospital #3

Chelyabinsk, 454106, Russia

Location

Kazan State Medical University based on Republican Clinical Hospital

Kazan', 420029, Russia

Location

Clinical Hospital #3

Kemerovo, 650000, Russia

Location

Euromedservice, Clinical and Diagnostic Center

Moscow, 115419, Russia

Location

MONIKI

Moscow, 129110, Russia

Location

City Clinical Hospital #1 n.a. A.N. Kabanov

Omsk, 644112, Russia

Location

Vvedenskaya hospital

Saint Petersburg, 191180, Russia

Location

Medical Center "Reavita Med SPb"

Saint Petersburg, 194354, Russia

Location

FSBEI HE First Pavlov Medical University

Saint Petersburg, 197022, Russia

Location

Medical Association "NEW HOSPITAL"

Yekaterinburg, 620109, Russia

Location

Soonchunhyang University Bucheon Hospital

Bucheon-si, Gyeonggi-do, 14579, South Korea

Location

The Catholic University of Korea, Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-do, 14647, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Ajou University Hospital

Suwon, Gyeonggi-do, 16499, South Korea

Location

Inje University Busan Paik Hospital

Busan, 47392, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Korea University Anam Hospital

Seoul, 2841, South Korea

Location

Seoul National University Hospital

Seoul, 3080, South Korea

Location

Asan Medical Center

Seoul, 5505, South Korea

Location

Samsung Medical Centerx

Seoul, 6351, South Korea

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare

Taipei, 23561, Taiwan

Location

Related Publications (2)

• Raghu G, Richeldi L, Fernandez Perez ER, De Salvo MC, Silva RS, Song JW, Ogura T, Xu ZJ, Belloli EA, Zhang X, Seid LL, Poole L; ZEPHYRUS-1 Study Investigators. Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial. JAMA. 2024 Aug 6;332(5):380-389. doi: 10.1001/jama.2024.8693.

  PMID: 38762797 DERIVED

• Rayego-Mateos S, Morgado-Pascual JL, Lavoz C, Rodrigues-Diez RR, Marquez-Exposito L, Tejera-Munoz A, Tejedor-Santamaria L, Rubio-Soto I, Marchant V, Ruiz-Ortega M. CCN2 Binds to Tubular Epithelial Cells in the Kidney. Biomolecules. 2022 Feb 3;12(2):252. doi: 10.3390/biom12020252.

  PMID: 35204752 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Idiopathic Interstitial Pneumonias; Lung Diseases, Interstitial; Pulmonary Fibrosis

Interventions

pamrevlumab

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Study did not meet its primary endpoint; hence, it was terminated early. The Japan extension cohort and OLE period were halted due to futility.

Results Point of Contact

• Title: Clinical Trial Information Desk
• Organization: FibroGen, Inc.

zephyrus@fibrogen.com

415-978-1441

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2019
• First Posted: May 17, 2019
• Study Start: June 18, 2019
• Primary Completion: March 20, 2023
• Study Completion: August 28, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

CN (22); RU (10); HK (2); AU (6); AR (9); US (60); KR (10); TW (2); CL (4)