Idiopathic Pulmonary FibrosisPhase 3NCT03955146
Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
A Phase 3 study testing Pamrevlumab in people with Idiopathic Pulmonary Fibrosis, run by Kyntra Bio at 125 sites in 9 countries.
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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis
- What is being tested?
- Pamrevlumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 393 participants
- Where
- 125 sitesin 9 countries
- Study dates
- 18 Jun 2019to 28 Aug 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
125 sites in 9 countries.
125 sites in 9 countries
United States60 sites
Albany Medical College
Albany, New York, 12208
University of Michigan
Ann Arbor, Michigan, 48109
Emory University
Atlanta, Georgia, 30322
University of Colorado Denver
Aurora, Colorado, 80045
Piedmont Healthcare, Inc.
Austell, Georgia, 30106
University of Maryland, Baltimore
Baltimore, Maryland, 21201
University of Alabama at Birmingham Hospital
Birmingham, Alabama, 35294
The University of Vermont
Burlington, Vermont, 05405
Lowcountry Lung and Critical Care, PA
Charleston, South Carolina, 29406
Medical University of South Carolina
Charleston, South Carolina, 29425
The Lung Research Center, LLC
Chesterfield, Missouri, 63017
Northwestern University
Chicago, Illinois, 60612
University of Cincinnati
Cincinnati, Ohio, 45267
St. Francis Medical Center
Clearwater, Florida, 33765
Ohio State University
Columbus, Ohio, 43221
J&L Research
Conway, Arkansas, 72032
Houston Pulmonary Sleep, Allergy and Asthma Associates
Cypress, Texas, 77429
Baylor Scott and White Research Institute
Dallas, Texas, 75246
University of Texas Southwestern Medical Center
Dallas, Texas, 75390
National Jewish Health
Denver, Colorado, 80207
Henry Ford Hospital
Detroit, Michigan, 48202
University of Florida Pulmonary, Critical Care & Sleep Medicine Division
Gainesville, Florida, 32610
Spectrum Health
Grand Rapids, Michigan, 49546
Pulmonix, LLC
Greensboro, North Carolina, 27403
Tennessee Comprehensive Lung and Sleep Center
Hendersonville, Tennessee, 37075
Penn State Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033
Baylor College of Medicine
Houston, Texas, 77030
University of Texas - Houston
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
University of Florida Health, Jacksonville
Jacksonville, Florida, 32209
Mayo Clinic
Jacksonville, Florida, 32224
The University of Kansas Medical Center
Kansas City, Kansas, 66160
Pulmonary Disease Specialist, PA d/b/a, PDS Research
Kissimmee, Florida, 34741
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
Pulmonary Health Physicians, PC
Liverpool, New York, 13088
Loma Linda University Health
Loma Linda, California, 92354
David Geffen School of Medicine at UCLA
Los Angeles, California, 90095
Loyola University of Chicago
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
University of Minnesota
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center
Nashville, Tennessee, 37204
Yale University School of Medicine
New Haven, Connecticut, 06510
INTEGRIS Baptist Medical Center
Oklahoma City, Oklahoma, 73112
Temple University
Philadelphia, Pennsylvania, 19140
Banner University Medical Center - Phoenix
Phoenix, Arizona, 85006
Norton Thoracic Institute
Phoenix, Arizona, 85013
Pulmonary Associates, PA - Research
Phoenix, Arizona, 85032
Legacy Research Institute
Portland, Oregon, 97210
The Oregon Clinic
Portland, Oregon, 97220
Rhode Island Hospital
Providence, Rhode Island, 02903
UC Davis Medical Center
Sacramento, California, 95817
University of Utah Health
Salt Lake City, Utah, 84108
UT Health San Antonio
San Antonio, Texas, 78229
University of California San Diego
San Diego, California, 92103
University of Washington
Seattle, Washington, 98195
Stanford University Medical Center
Stanford, California, 94305
University of South Florida
Tampa, Florida, 33606
Renovatio Clinical
The Woodlands, Texas, 77380
University of Arizona
Tucson, Arizona, 85724
Medstar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
China22 sites
BeiJing Chao-Yang Hospital,Capital medical university
Beijing, Beijing Municipality, 100020
China-Japan friendship hospital
Beijing, Beijing Municipality, 100029
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
The Second Xiangya Hospital of Central South University
Changsha, Hunan, 410011
Huaxi Hospital of Sichuan University.
Chengdu, Sichuan, 6100141
The second hospital of Dalian medical university
Dalian, Liaoning, 116001
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, 510000
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
Hangzhou First People's Hospital
Hangzhou, Zhejiang, 310006
Second Affiliated Hospital of Anhui Medical University
Hefei, Anhui, 230000
Affiliated Hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia, 10010
People's Hospital of Inner Mongolia Autonomous Region
Hohhot, Inner Mongolia, 10020
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
The First Hospital of China Medical University
Shenyang, Liaoning, 110001
Shenzhen people's hospital
Shenzhen, Guangdong, 518020
General Hospital of Tianjin Medical University
Tianjin, Tianjin Municipality, 300052
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Union Hospital,Tongji Medical College of Huazhong University of Science and Technology
Wuhan, Hubei, 430022
The Second Affiliated Hospital of Xi'an Jiaotong University
Xi’an, Shanxi, 710004
General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750004
Henan Provincial People's Hospital
Zhengzhou, Henan, 450000
Henan Provincial chest hospital
Zhengzhou, Henan, 450003
Russia10 sites
Regional Clinical Hospital #3
Chelyabinsk, 454106
Kazan State Medical University based on Republican Clinical Hospital
Kazan', 420029
Clinical Hospital #3
Kemerovo, 650000
Euromedservice, Clinical and Diagnostic Center
Moscow, 115419
MONIKI
Moscow, 129110
City Clinical Hospital #1 n.a. A.N. Kabanov
Omsk, 644112
Vvedenskaya hospital
Saint Petersburg, 191180
Medical Center "Reavita Med SPb"
Saint Petersburg, 194354
FSBEI HE First Pavlov Medical University
Saint Petersburg, 197022
Medical Association "NEW HOSPITAL"
Yekaterinburg, 620109
South Korea10 sites
Soonchunhyang University Bucheon Hospital
Bucheon-si, Gyeonggi-do, 14579
The Catholic University of Korea, Bucheon St. Mary's Hospital
Bucheon-si, Gyeonggi-do, 14647
Inje University Busan Paik Hospital
Busan, 47392
Gachon University Gil Medical Center
Incheon, 21565
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Korea University Anam Hospital
Seoul, 2841
Seoul National University Hospital
Seoul, 3080
Asan Medical Center
Seoul, 5505
Samsung Medical Centerx
Seoul, 6351
Ajou University Hospital
Suwon, Gyeonggi-do, 16499
Argentina9 sites
Centro de Investigacion Metabolica 'CINME'
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1027AAP
Consultorios Medicos. Organización del Buen Ayre. SRL
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1425FVH
Fundacion Respirar - Centro Médico Dra. De Salvo
Ciudad Autonoma de Buenos Aires (caba), Buenos Aires, 1426
Centro Medico de Enfermedades Respiratorias
Florida, Buenos Aires, B1602DQD
Respira Salud Clinica Integral
Godoy Cruz, Mendoza Province, M5501GCA
Centro Platense en Investigaciones Respiratorias
La Plata, Buenos Aires, 1900
Instituto ave Pulmo Fundacion enfisema
Mar del Plata, Buenos Aires, B7602DCK
INSARES
Mendoza, Mendoza Province, M5500CCG
Investigaciones en Patologias Respiratorias
San Miguel de Tucumán, Tucumán Province, T4000IAR
Australia6 sites
Royal Adelaide Hospital
Adelaide, South Australia, 5000
Box Hill Hospital
Box Hill, Victoria, 3128
The Alfred Hospital
Melbourne, Victoria, 3004
Mater Health Services Adult Hospital
South Brisbane, Queensland, 4101
Royal Prince Alfred Hospital
Sydney, New South Wales, 2050
Westmead Hospital
Westmead, New South Wales, 2145
Chile4 sites
Instituto Nacional del Torax
Santiago, Santiago Metropolitan, 7500691
CIMER
Santiago, Santiago Metropolitan, 7500692
M y F estudios clinicos
Santiago, Santiago Metropolitan, 7750495
Centro Investigacion del Maule CIM
Talca, Maule Region, 3465586
Taiwan2 sites
Taichung Veterans General Hospital
Taichung, 40705
Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare
Taipei, 23561
About this study
Official title: 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.
Read the 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:
- 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.
- Conditions
- Idiopathic Pulmonary Fibrosis
- Being tested
- Pamrevlumab, Placebo
- Keywords
- Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Lung Fibrosis
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Idiopathic Interstitial Pneumonias, Lung Diseases, Interstitial, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PamrevlumabDrug
Also called FG-3019
Pamrevlumab will be administered per dose and schedule specified in the arm description.
PlaceboDrug
Placebo matching to pamrevlumab will be administered per schedule specified in the arm description.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Pamrevlumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: Baseline, Week 48
Secondary outcomes (6)
DB Period (Main Study Cohort): Time to Disease Progression
Time to disease progression was defined as the number of weeks from randomization to either the first occurrence of an absolute ≥10% decline from baseline in percent predicted FVC (FVCpp) or all-cause death, whichever occurred first. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Measured: Up to Week 48
DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint
The components of the clinical composite endpoint included acute IPF exacerbation, respiratory hospitalization, or death. Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Measured: 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
The QLF volume was calculated as QLF = total lung capacity volume multiplied by percentage (%) of quantitative lung fibrosis for fibrosis of the whole lung. LS mean and SE was calculated using MMRM.
Measured: Baseline, Week 48
DB Period (Main Study Cohort): Time to First Acute IPF Exacerbation
Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Measured: Up to Week 48
DB Period (Main Study Cohort): Time to All-Cause Mortality
Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Measured: Up to Week 48
DB Period (Main Study Cohort): Time to First Respiratory Hospitalizations
Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. Hence, the 'Median Time to Event' is longer than the reported timeframe of 48 weeks.
Measured: Up to Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2019
- Study start18 Jun 2019
- Primary completion20 Mar 2023
- Study completion28 Aug 2023
Why it stopped: Study did not meet its primary endpoint.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 393 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kyntra Bio
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03955146
- Sponsor's protocol ID
- FGCL-3019-091
- Status last verified
- Sep 2024
- First submitted
- 16 May 2019
- Last updated
- 19 Sep 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38762797Rayego-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.
PubMed 35204752
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
- ClinicalTrials.gov ID
- NCT03955146
- Acronym / sponsor ID
- FGCL-3019-091
- Conditions
- Idiopathic Pulmonary Fibrosis
- Keywords
- Idiopathic Pulmonary Fibrosis, IPF, Idiopathic Interstitial Pneumonia, Interstitial Lung Disease, Lung Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study did not meet its primary endpoint.
- Enrolment
- 393 participants (actual)
- Lead sponsor
- Kyntra BioIndustry (pharma, biotech, devices)
- Study start
- 18 Jun 2019 (actual)
- Primary completion
- 20 Mar 2023 (actual)
- Study completion
- 28 Aug 2023 (actual)
- First posted
- 17 May 2019 (actual)
- Results
- Posted 19 Sep 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Main Study Cohort: Pamrevlumab | Experimental | Drug: PamrevlumabParticipants will receive pamrevlumab 30 milligrams (mg)/kilogram (kg) by intravenous (IV) infusion every 3 weeks for up to 48 weeks in the DB period. |
| Main Study Cohort: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks in the DB period. |
| Japan Extension Cohort: Pamrevlumab | Experimental | Drug: PamrevlumabParticipants will receive pamrevlumab 30 mg/kg by IV infusion every 3 weeks for up to 48 weeks. |
| Japan Extension Cohort: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive placebo matching to pamrevlumab by IV infusion every 3 weeks for up to 48 weeks. |
| OLE Period: Pamrevlumab/Pamrevlumab | Experimental | Drug: PamrevlumabParticipants 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. |
| OLE Period: Placebo/Pamrevlumab | Experimental | Drug: PamrevlumabParticipants 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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PamrevlumabAlso: FG-3019Pamrevlumab will be administered per dose and schedule specified in the arm description. | Drug | Japan Extension Cohort: Pamrevlumab, Main Study Cohort: Pamrevlumab, OLE Period: Pamrevlumab/Pamrevlumab, OLE Period: Placebo/Pamrevlumab |
| PlaceboPlacebo matching to pamrevlumab will be administered per schedule specified in the arm description. | Drug | Japan Extension Cohort: Placebo, Main Study Cohort: Placebo |
Primary outcome
DB Period (Main Study Cohort): Change From Baseline in FVC at Week 48
Time frame: Baseline, 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).
DB Period (Japan Extension Cohort): Change From Baseline in FVC at Week 48
Time frame: Baseline, 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.
6 secondary outcomes
DB Period (Main Study Cohort): Time to Disease Progression
Time frame: Up to Week 48
DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint
Time frame: 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
Time frame: Baseline, Week 48
DB Period (Main Study Cohort): Time to First Acute IPF Exacerbation
Time frame: Up to Week 48
DB Period (Main Study Cohort): Time to All-Cause Mortality
Time frame: Up to Week 48
DB Period (Main Study Cohort): Time to First Respiratory Hospitalizations
Time frame: Up to Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38762797Raghu 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.
- Derived from this study: PubMed 35204752Rayego-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.
- Individual participant dataSharing planned: Undecided
Related trials for Idiopathic Pulmonary Fibrosis
RecruitingPhase 2
Study to Evaluate the Efficacy, Safety, and Tolerability of PIPE 791 in Subjects With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
RecruitingPhase 2
An Extension Study of Subjects Who Received an Avalyn Inhaled Antifibrotic Agent (SAIL)
Progressive Pulmonary Fibrosis, Idiopathic Pulmonary Fibrosis (IPF)
RecruitingObservational study
Real-world Study of Nerandomilast in Patients With Idiopathic Pulmonary Fibrosis and Progressive Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF), Progressive Pulmonary Fibrosis
RecruitingPhase 2
A Phase 2 Study of LTI-03 in Patients With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF)
Not yet recruitingPhase 2
A Phase 2 Study of HB0056 in Patients With Idiopathic Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis (IPF)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
125 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pamrevlumab in people with Idiopathic Pulmonary Fibrosis, run by Kyntra Bio at 125 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 125 sites in United States, China, Russia, South Korea, Argentina and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DB Period (Main Study Cohort): Change From Baseline in FVC at Week 48 (time frame: Baseline, Week 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03955146, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.