Clinical trial NCT03955146: Zephyrus I: Evaluation of Efficacy and Safety of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Official title: 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: 2019-05-17
Enrollment: 393
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 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:

  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.

Eligibility criteria: 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.

Primary outcomes:
measure: DB Period (Main Study Cohort): Change From Baseline in FVC at Week 48
timeFrame: Baseline, Week 48
measure: DB Period (Japan Extension Cohort): Change From Baseline in FVC at Week 48
timeFrame: Baseline, Week 48
Secondary outcomes:
measure: DB Period (Main Study Cohort): Time to Disease Progression
timeFrame: Up to Week 48
measure: DB Period (Main Study Cohort): Time to First Occurrence of Any Component of the Clinical Composite Endpoint
timeFrame: Up to Week 48
measure: DB Period (Main Study Cohort and Japan Extension Cohort): Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48
timeFrame: Baseline, Week 48
measure: DB Period (Main Study Cohort): Time to First Acute IPF Exacerbation
timeFrame: Up to Week 48
measure: DB Period (Main Study Cohort): Time to All-Cause Mortality
timeFrame: Up to Week 48
measure: DB Period (Main Study Cohort): Time to First Respiratory Hospitalizations
timeFrame: Up to Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham Hospital
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medical Center - Phoenix
state: Arizona
city: Phoenix
country: United States
facility: Norton Thoracic Institute
state: Arizona
city: Phoenix
country: United States
facility: Pulmonary Associates, PA - Research
state: Arizona
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Conway
country: United States
facility: J&L Research
state: Arkansas
city: Loma Linda
country: United States
facility: Loma Linda University Health
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Medstar Georgetown University Hospital
state: District of Columbia
city: Clearwater
country: United States
facility: St. Francis Medical Center
state: Florida
city: Gainesville
country: United States
facility: University of Florida Pulmonary, Critical Care & Sleep Medicine Division
state: Florida
city: Jacksonville
country: United States
facility: University of Florida Health, Jacksonville
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialist, PA d/b/a, PDS Research
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Austell
country: United States
facility: Piedmont Healthcare, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Maywood
country: United States
facility: Loyola University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland, Baltimore
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Chesterfield
country: United States
facility: The Lung Research Center, LLC
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Liverpool
country: United States
facility: Pulmonary Health Physicians, PC
state: New York
city: Greensboro
country: United States
facility: Pulmonix, LLC
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Baptist Medical Center
state: Oklahoma
city: Portland
country: United States
facility: Legacy Research Institute
state: Oregon
city: Portland
country: United States
facility: The Oregon Clinic
state: Oregon
city: Hershey
country: United States
facility: Penn State Milton S. Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Lowcountry Lung and Critical Care, PA
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Hendersonville
country: United States
facility: Tennessee Comprehensive Lung and Sleep Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Cypress
country: United States
facility: Houston Pulmonary Sleep, Allergy and Asthma Associates
state: Texas
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: University of Texas - Houston
state: Texas
city: San Antonio
country: United States
facility: UT Health San Antonio
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah Health
state: Utah
city: Burlington
country: United States
facility: The University of Vermont
state: Vermont
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Ciudad Autonoma De Buenos Aires (caba)
country: Argentina
facility: Fundacion Respirar - Centro Médico Dra. De Salvo
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Centro de Investigacion Metabolica 'CINME'
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Consultorios Medicos. Organización del Buen Ayre. SRL
state: Buenos Aires
city: Florida
country: Argentina
facility: Centro Medico de Enfermedades Respiratorias
state: Buenos Aires
city: La Plata
country: Argentina
facility: Centro Platense en Investigaciones Respiratorias
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Instituto ave Pulmo Fundacion enfisema
state: Buenos Aires
city: Ciudad de Mendoza
country: Argentina
facility: INSARES
state: Mendoza
city: Godoy Cruz
country: Argentina
facility: Respira Salud Clinica Integral
state: Provincia De Mendoza
city: San Miguel De Tucumán
country: Argentina
facility: Investigaciones en Patologias Respiratorias
state: Tucumán
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Health Services Adult Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Talca
country: Chile
facility: Centro Investigacion del Maule CIM
state: Region Del Maule
city: Santiago
country: Chile
facility: Instituto Nacional del Torax
state: Region Metropolitana
city: Santiago
country: Chile
facility: CIMER
state: Region Metropolitana
city: Santiago
country: Chile
facility: M y F estudios clinicos
state: Region Metropolitana
city: Hefei
country: China
facility: Second Affiliated Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: BeiJing Chao-Yang Hospital,Capital medical university
state: Beijing
city: Beijing
country: China
facility: China-Japan friendship hospital
state: Beijing
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen people's hospital
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial chest hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Union Hospital，Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Hohhot
country: China
facility: Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Hohhot
country: China
facility: People's Hospital of Inner Mongolia Autonomous Region
state: Inner Mongolia
city: Dalian
country: China
facility: The second hospital of Dalian medical university
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: ChenDu
country: China
facility: Huaxi Hospital of Sichuan University.
state: Sichuan
city: Tianjin
country: China
facility: General Hospital of Tianjin Medical University
state: Tianjin
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital
state: Zhejiang
city: Central
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Tuen Mun Hospital
city: Bucheon-si
country: Korea, Republic of
facility: Soonchunhyang University Bucheon Hospital
state: Gyeonggi-do
city: Bucheon-si
country: Korea, Republic of
facility: The Catholic University of Korea, Bucheon St. Mary's Hospital
state: Gyeonggi-do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyeonggi-do
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Centerx
city: Chelyabinsk
country: Russian Federation
facility: Regional Clinical Hospital #3
city: Ekaterinburg
country: Russian Federation
facility: Medical Association "NEW HOSPITAL"
city: Kazan
country: Russian Federation
facility: Kazan State Medical University based on Republican Clinical Hospital
city: Kemerovo
country: Russian Federation
facility: Clinical Hospital #3
city: Moscow
country: Russian Federation
facility: Euromedservice, Clinical and Diagnostic Center
city: Moscow
country: Russian Federation
facility: MONIKI
city: Omsk
country: Russian Federation
facility: City Clinical Hospital #1 n.a. A.N. Kabanov
city: Saint-Petersburg
country: Russian Federation
facility: FSBEI HE First Pavlov Medical University
city: St. Petersburg
country: Russian Federation
facility: Vvedenskaya hospital
city: St. Petersburg
country: Russian Federation
facility: Medical Center "Reavita Med SPb"
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University - Shuang-Ho Hospital, Ministry of Health and Welfare
Study officials:
References:
citation: 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.