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

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 IPF.

Study Overview

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

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 356
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires
    • Ciudad Autonoma De Buenos Aires (caba), Buenos Aires, Argentina, 1426
      • Fundacion Respirar - Centro Médico Dra. De Salvo
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1027AAP
      • Centro de Investigacion Metabolica 'CINME'
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425FVH
      • Consultorios Medicos. Organización del Buen Ayre. SRL
    • Florida, Buenos Aires, Argentina, B1602DQD
      • Centro Medico de Enfermedades Respiratorias
    • La Plata, Buenos Aires, Argentina, 1900
      • Centro Platense en Investigaciones Respiratorias
    • Mar del Plata, Buenos Aires, Argentina, B7602DCK
      • Instituto ave Pulmo Fundacion enfisema
  • Mendoza
    • Ciudad de Mendoza, Mendoza, Argentina, M5500CCG
      • INSARES
  • Provincia De Mendoza
    • Godoy Cruz, Provincia De Mendoza, Argentina, M5501GCA
      • Respira Salud Clinica Integral
  • Tucumán
    • San Miguel De Tucumán, Tucumán, Argentina, T4000IAR
      • Investigaciones en Patologias Respiratorias
• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Health Services Adult Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Chile
  • Region Del Maule
    • Talca, Region Del Maule, Chile, 3465586
      • Centro Investigacion del Maule CIM
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7500691
      • Instituto Nacional del Tórax
    • Santiago, Region Metropolitana, Chile, 7500692
      • CIMER
    • Santiago, Region Metropolitana, Chile, 7750495
      • M y F estudios clinicos
• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Second Affiliated hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100029
      • China-Japan Friendship Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital,Capital medical university
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • The First Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China, 510000
      • Nanfang Hospital of Southern Medical University
    • Shenzhen, Guangdong, China, 518020
      • Shenzhen People's Hospital
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Provincial People's Hospital
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial Chest Hospital
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430022
      • Union Hospital，Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital Of Central South University
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China, 10010
      • Affiliated Hospital of Inner Mongolia Medical University
    • Hohhot, Inner Mongolia, China, 10020
      • People's Hospital of Inner Mongolia Autonomous Region
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • The Second Hospital of Dalian Medical University
    • Shenyang, Liaoning, China, 110001
      • The First Hospital of China Medical University
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • General Hospital of Ningxia Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
  • Shanxi
    • Xi'an, Shanxi, China, 710004
      • The Second Affiliated Hospital of Xi'an Jiaotong University
  • Sichuan
    • ChenDu, Sichuan, China, 6100141
      • Huaxi Hospital of Sichuan University.
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • General Hospital of Tianjin Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Hangzhou First People's Hospital
• Hong Kong
  • Central, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Tuen Mun Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 3080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 5505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 2841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 6351
    • Samsung Medical Centerx
  • Gyeonggi-do
    • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14579
      • Soonchunhyang University Bucheon Hospital
    • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647
      • The Catholic University of Korea, Bucheon St. Mary's Hospital
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
    • Suwon-si, Gyeonggi-do, Korea, Republic of, 16499
      • Ajou University Hospital
• Russian Federation
  • Chelyabinsk, Russian Federation, 454106
    • Regional Clinical Hospital #3
  • Ekaterinburg, Russian Federation, 620109
    • Medical Association "NEW HOSPITAL"
  • Kazan, Russian Federation, 420029
    • Kazan State Medical University based on Republican Clinical Hospital
  • Kemerovo, Russian Federation, 650000
    • Clinical Hospital #3
  • Moscow, Russian Federation, 115419
    • Euromedservice, Clinical and Diagnostic Center
  • Moscow, Russian Federation, 129110
    • MONIKI
  • Omsk, Russian Federation, 644112
    • City Clinical Hospital #1 n.a. A.N. Kabanov
  • Saint-Petersburg, Russian Federation, 197022
    • FSBEI HE First Pavlov Medical University
  • St. Petersburg, Russian Federation, 191180
    • Vvedenskaya hospital
  • St. Petersburg, Russian Federation, 194354
    • Medical Center "Reavita Med SPb"
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taipei, Taiwan, 23561
    • Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center - Phoenix
    • Phoenix, Arizona, United States, 85013
      • Norton Thoracic Institute
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates, PA - Research
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • Arkansas
    • Conway, Arkansas, United States, 72032
      • J&L Research
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Health
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
    • San Diego, California, United States, 92103
      • University of California San Diego
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Denver, Colorado, United States, 80207
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Florida
    • Clearwater, Florida, United States, 33765
      • St. Francis Medical Center
    • Gainesville, Florida, United States, 32610
      • University of Florida Pulmonary, Critical Care & Sleep Medicine Division
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health, Jacksonville
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialist, PA d/b/a, PDS Research
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
    • Austell, Georgia, United States, 30106
      • Piedmont Healthcare, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Northwestern University
    • Maywood, Illinois, United States, 60153
      • Loyola University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Baltimore
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Grand Rapids, Michigan, United States, 49546
      • Spectrum Health
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • The Lung Research Center, LLC
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Liverpool, New York, United States, 13088
      • Pulmonary Health Physicians, PC
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • Pulmonix, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Columbus, Ohio, United States, 43221
      • Ohio State University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Integris Baptist Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Research Institute
    • Portland, Oregon, United States, 97220
      • The Oregon Clinic
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29406
      • Lowcountry Lung and Critical Care, PA
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Tennessee Comprehensive Lung and Sleep Center
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt University Medical Center
  • Texas
    • Cypress, Texas, United States, 77429
      • Houston Pulmonary Sleep, Allergy and Asthma Associates
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75246
      • Baylor Scott and White Research Institute
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • University of Texas - Houston
    • San Antonio, Texas, United States, 78229
      • UT Health San Antonio
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Vermont
    • Burlington, Vermont, United States, 05405
      • The University of Vermont
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

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 (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.

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; Pamrevlumab 30 mg/kg by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks	Drug: Pamrevlumab; Pamrevlumab will be administered per dose and schedule specified in the arm description.; Other Names: FG-3019
Experimental: Placebo; Placebo matching to pamrevlumab by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks	Drug: Placebo; Placebo matching to pamrevlumab will be administered per schedule specified in the arm description.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Forced Vital Capacity (FVC) at Week 48	Baseline, Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48		Baseline, Week 48
Time to Any Component of the Clinical Composite Endpoint, Whichever Occurs First: Acute IPF Exacerbation, Respiratory Hospitalization, or Death		Baseline to Week 48
Time to First Acute IPF Exacerbation During Study		Baseline to Week 48
Time to All-cause Mortality During Study		Baseline to Week 48
Time to First Respiratory Hospitalizations During Study		Baseline to Week 48

Collaborators and Investigators

• Sponsor: FibroGen

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2019
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: May 16, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, 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-3019-091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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