Evaluate the Safety and Efficacy of FG-3019 (Pamrevlumab) in Participants With Idiopathic Pulmonary Fibrosis (IPF)

NCT ID: NCT01890265

Last Updated: 2020-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-30
• Study Completion Date: 2017-11-16

Brief Summary

To evaluate the safety and tolerability of pamrevlumab in participants with IPF, and the efficacy of pamrevlumab in slowing the loss of forced vital capacity (FVC) and the progression of IPF in these participants.

Detailed Description

The study has been amended in February 2016 to further allow for the enrollment of a subgroup of participants (N=60) who will be allowed to receive treatment with approved IPF therapy with pirfenidone or with nintedanib as concomitant therapy.

These additional participants will be stratified by background therapy, randomized to pamrevlumab or placebo, and followed up for 24 weeks. The main objective of the study remains safety. Pharmacokinetic (PK) samples to assess drug concentrations will also be collected.

This sub-study portion only applies to a select United States centers.

Enrollment for the main study was completed on 29 June 2016. Enrollment for the sub-study was completed on 16 December 2016.

Conditions

Idiopathic Pulmonary Fibrosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pamrevlumab

Participants will receive pamrevlumab 30 milligram/kilogram (mg/kg) by intravenous (IV) infusion every 3 weeks for a total of 16 infusions over 45 weeks.

Group Type: EXPERIMENTAL

Pamrevlumab

Intervention Type: DRUG

Solution for infusion

Placebo

Participants will receive placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 16 infusions over 45 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for infusion

Sub-Study: Pamrevlumab+Pirfenidone or Nintedanib

Participants will receive pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with pamrevlumab in all active comparator participants will be administered at a dose of 15 mg/kg for the first 2 dose administrations. If these are well tolerated, all following study drug administrations will be at 30 mg/kg.

Pirfenidone or nintedanib will be dosed according to the instructions in their respective labels and the prescribing physician.

Group Type: ACTIVE_COMPARATOR

Pamrevlumab

Intervention Type: DRUG

Solution for infusion

Sub-Study: Pirfenidone

Intervention Type: DRUG

Pirfenidone concomitant therapy will not be provided by the Sponsor.

Sub-Study: Nintedanib

Intervention Type: DRUG

Nintedanib concomitant therapy will not be provided by the Sponsor.

Sub-Study: Placebo+Pirfenidone or Nintedanib

Participants will receive placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 8 infusions over 21 weeks. Initial treatment with placebo in all active comparator participants will be administered at a dose of 15 mg/kg for the first 2 dose administrations. If these are well tolerated, all following study drug administrations will be at 30 mg/kg.

Pirfenidone or nintedanib will be dosed according to the instructions in their respective labels and the prescribing physician.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Solution for infusion

Sub-Study: Pirfenidone

Intervention Type: DRUG

Pirfenidone concomitant therapy will not be provided by the Sponsor.

Sub-Study: Nintedanib

Intervention Type: DRUG

Nintedanib concomitant therapy will not be provided by the Sponsor.

Interventions

Pamrevlumab

Solution for infusion

Intervention Type: DRUG

Placebo

Solution for infusion

Intervention Type: DRUG

Sub-Study: Pirfenidone

Pirfenidone concomitant therapy will not be provided by the Sponsor.

Intervention Type: DRUG

Sub-Study: Nintedanib

Nintedanib concomitant therapy will not be provided by the Sponsor.

Intervention Type: DRUG

Other Intervention Names

Fully human recombinant immunoglobulin G (IgG), kappa monoclonal anti-body.; FG-3019; Esbeiet; Ofev

Eligibility Criteria

Inclusion Criteria

1. Age 40 to 80 years, inclusive.

2. Diagnosis of IPF as defined by current international guidelines. Each participant must have 1 of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available high-resolution computed tomography (HRCT) scan; or (2) Possible UIP Pattern on an available HRCT scan and surgical lung biopsy within 4 years of Screening showing UIP Pattern.

3. History of IPF of ≤5 years duration with onset defined as the date of the first diagnosis of IPF by HRCT or surgical lung biopsy.

4. Interstitial pulmonary fibrosis defined by HRCT scan at Screening, with evidence of ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing, within the whole lung, as determined by the HRCT central reader.

5. FVC percent of predicted value ≥55% at Screening.

6. Female participants of childbearing potential (including those <1 year postmenopausal) must be willing to use a medically acceptable method of contraception, for example, an oral contraceptive, depot progesterone, or intrauterine device. Male participants with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (for example, condom) if not surgically sterile (for example, vasectomy).

7. For sub-study only: Receiving treatment for IPF with a stable dose of pirfenidone or with a stable dose of nintedanib for at least 3 months before Screening initiation and willing to continue treatment with pirfenidone or with nintedanib according to the corresponding approved label and the prescribing physician, including all listed safety requirements (for example, liver function tests, avoidance of sunlight and sunlamp exposure and wearing of sunscreen and protective clothing daily for pirfenidone, and smoking cessation).

Exclusion Criteria

1. Women who are pregnant or nursing.

2. Infiltrative lung disease other than IPF, including any of the other types of idiopathic interstitial pneumonias (Travis, 2013); lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis and connective tissue diseases.

3. HRCT scan findings at Screening are inconsistent with UIP Pattern, as determined by the HRCT central reader.

4. Pathology diagnosis on surgical lung biopsy is anything other than UIP Pattern, as determined by the local pathologist.

5. The Investigator judges that there has been sustained improvement in the severity of IPF during the 12 months prior to Screening, based on changes in FVC, diffusing capacity of the lung for carbon monoxide (DLCO), and/or HRCT scans of the chest.

6. Clinically important abnormal laboratory tests.

7. Upper or lower respiratory tract infection of any type within 4 weeks of the first Screening visit.

8. Acute exacerbation of IPF within 3 months of the first Screening visit.

9. Use of medications to treat IPF within 5 half-lives of Day 1 dosing. If monoclonal antibodies were used, the last dose of the antibody must be at least 4 weeks before Day 1 dosing. This applies to participants enrolled in Main Study only.

10. Use of any investigational drugs, including any investigational drugs for IPF, within 4 weeks prior to Day 1 dosing.

11. History of cancer diagnosis of any type in the 3 years preceding Screening, excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cancers.

12. Diffusing capacity (DLCO) less than 30% of predicted value.

13. History of allergic or anaphylactic reaction to human, humanized, chimeric, or murine monoclonal antibodies.

14. Previous treatment with FG-3019.

15. Body weight greater than 130 kilograms.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FibroGen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Wencel, M.D

Role: PRINCIPAL_INVESTIGATOR

Via Christi Clinic, P.A., USA

Joao de Andrade, M.D

Role: PRINCIPAL_INVESTIGATOR

The Kirklin Clinic, USA

Peter LaCamera, M.D.

Role: PRINCIPAL_INVESTIGATOR

Steward St. Elizabeth's Medical Center, USA

Danielle Antin-Ozerkis, M.D.

Role: PRINCIPAL_INVESTIGATOR

Yale University, USA

Rishi Raj, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Neil Ettinger, M.D

Role: PRINCIPAL_INVESTIGATOR

St Luke's Hospital, USA

Rafael Perez, M.D

Role: PRINCIPAL_INVESTIGATOR

University of Louisville, USA

Timothy Albertson, M.D

Role: PRINCIPAL_INVESTIGATOR

University of California Davis Medical Center, USA

Yolanda Mageto, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vermont Lung Center, USA

Srihari Veeraraghavan, M.D

Role: PRINCIPAL_INVESTIGATOR

Emory University, USA

Nishant Gupta, M.D

Role: PRINCIPAL_INVESTIGATOR

University of Cinncinati, USA

Kevin Gibson, M.D

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh Medical Center, USA

Lisa Lancaster, M.D.

Role: PRINCIPAL_INVESTIGATOR

Vanderbilt University, USA

Mary Beth Scholand, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Utah - Lung Health Research, USA

Mark Hamblin, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center, USA

John Fitzgerald, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center, USA

John Belperio, M.D.

Role: PRINCIPAL_INVESTIGATOR

David Geffen School of Medicine at UCLA, USA

Richard Enelow, M.D.

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center, USA

Evans R Fernandez-Perez, M.D

Role: PRINCIPAL_INVESTIGATOR

National Jewish Center, USA

Peter A Bercz, M.D

Role: PRINCIPAL_INVESTIGATOR

Pensacola Research Consultants, INC., USA

Krishna Thavarajah, M.D.

Role: PRINCIPAL_INVESTIGATOR

Henry Ford Medical Center, USA

James Britt, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, College Park

Danielle D. Hosmer

Role: PRINCIPAL_INVESTIGATOR

Legacy Research Institute, USA

David Lederer, M.D.

Role: PRINCIPAL_INVESTIGATOR

Columbia University Medical Center, USA

Murali Ramaswamy, M.D.

Role: PRINCIPAL_INVESTIGATOR

PulmonIx LLC, USA

Thomas O'Brien, M.D.

Role: PRINCIPAL_INVESTIGATOR

Pulmonary Disease Specialist, PA, USA

Nadim Srour, M.D.

Role: PRINCIPAL_INVESTIGATOR

Université de Sherbrooke / Hôpital Charles LeMoyne, Canada

Elvis Irusen, M.D.

Role: PRINCIPAL_INVESTIGATOR

Tygerberg Hospital Respiratory Research Unit, South Africa

Anish Ambaram, M.D.

Role: PRINCIPAL_INVESTIGATOR

Life Mount Edgecombe Hospital, South Africa

Heidi Siebert, M.D.

Role: PRINCIPAL_INVESTIGATOR

Into Research, South Africa

Elizabeth Veitch, M.D.

Role: PRINCIPAL_INVESTIGATOR

Concord Repatriation, Australia

Huw Davies, M.D.

Role: PRINCIPAL_INVESTIGATOR

Daw Park Repatriation, Australia

Lutz Beckert, M.D.

Role: PRINCIPAL_INVESTIGATOR

Christchurch Hospital NZ, New Zealand

Catherina Chang, M.D.

Role: PRINCIPAL_INVESTIGATOR

Waikato Hospital, New Zealand

Benedict Brockway, M.D.

Role: PRINCIPAL_INVESTIGATOR

Dunedin Public Hospital, New Zealand

Suzanne Poole, M.D.

Role: PRINCIPAL_INVESTIGATOR

Tauranga Hospital, New Zealand

Raja Dhar, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fortis Hospitals, India

Bhanu Singh, M.D.

Role: PRINCIPAL_INVESTIGATOR

Midland Healthcare & Research Center, India

Nandagopal Velayuthaswamy, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sri Bala Medical Centre and Hospital, India

Sujeet Rajan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Bhatia Hospital, India

Priya Ramachandran, M.D.

Role: PRINCIPAL_INVESTIGATOR

St Johns Medical College Hospital, India

Natalia Stoeva, M.D.

Role: PRINCIPAL_INVESTIGATOR

MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology, Bulgaria

Locations

The Kirklin Clinic

Birmingham, Alabama, United States

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

UC Davis Medical Center

Sacramento, California, United States

National Jewish Health

Denver, Colorado, United States

Yale University

New Haven, Connecticut, United States

Pulmonary Disease Specialist, PA

Kissimmee, Florida, United States

Pensacola Research Consultants, Inc., d.b.a. Avanza Medical Research Center

Pensacola, Florida, United States

Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Via Christi Clinic, P.A.

Wichita, Kansas, United States

University of Louisville

Louisville, Kentucky, United States

University of Maryland

Baltimore, Maryland, United States

Steward St. Elizabeth's Medical Center

Boston, Massachusetts, United States

Henry Ford Medical Center

Detroit, Michigan, United States

St. Luke's Hospital

Chesterfield, Missouri, United States

Columbia University Medical Center

New York, New York, United States

PulmonIx LLC

Greensboro, North Carolina, United States

University of Cinncinati

Cincinnati, Ohio, United States

Dartmouth-Hitchcock Medical Center

Lebanon, Ohio, United States

Legacy Research Institute

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Utah - Lung Health Research

Salt Lake City, Utah, United States

Vermont Lung Center

Colchester, Vermont, United States

Concord Repatriation

Concord, New South Wales, Australia

Daw Park Repatriation

Adelaide, South Australia, Australia

MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology

Sofia, , Bulgaria

Université de Sherbrooke / Hôpital Charles LeMoyne

Greenfield Park, Quebec, Canada

St Johns Medical College Hospital

Bangalore, Karnataka, India

Bhatia Hospital

Mumbai, Maharashtra, India

Sri Bala Medical Centre and Hospital

Coimbatore, Tamil Nadu, India

Midland Healthcare & Research Center

Lucknow, Uttar Pradesh, India

Fortis Hospitals

Kolkata, West Bengal, India

Christchurch Hospital NZ

Christchurch, , New Zealand

Dunedin Public Hospital

Dunedin, , New Zealand

Waikato Hospital

Hamilton, , New Zealand

Tauranga Hospital

Tauranga, , New Zealand

Into Research

Pretoria, Gauteng, South Africa

Life Mount Edgecombe Hospital

Durban, KwaZulu-Natal, South Africa

Tygerberg Hospital Respiratory Research Unit

Cape Town, Western Cape, South Africa

Countries

United States; Australia; Bulgaria; Canada; India; New Zealand; South Africa

References

Lipson KE, Wong C, Teng Y, Spong S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S24. doi: 10.1186/1755-1536-5-S1-S24. eCollection 2012.

Reference Type: BACKGROUND

PMID: 23259531 (View on PubMed)

Kim GH, Zhang X, Brown MS, Poole L, Goldin J. Minimum clinically important difference in Quantitative Lung Fibrosis score associated with all-cause mortality in idiopathic pulmonary fibrosis: subanalysis from two phase II trials of pamrevlumab. BMJ Open. 2025 May 12;15(5):e094559. doi: 10.1136/bmjopen-2024-094559.

Reference Type: DERIVED

PMID: 40355288 (View on PubMed)

Richeldi L, Fernandez Perez ER, Costabel U, Albera C, Lederer DJ, Flaherty KR, Ettinger N, Perez R, Scholand MB, Goldin J, Peony Yu KH, Neff T, Porter S, Zhong M, Gorina E, Kouchakji E, Raghu G. Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2020 Jan;8(1):25-33. doi: 10.1016/S2213-2600(19)30262-0. Epub 2019 Sep 28.

Reference Type: DERIVED

PMID: 31575509 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan: Part 1

View Document

Document Type: Statistical Analysis Plan: Part 2

View Document

Other Identifiers

FGCL-3019-067

Identifier Type: -

Identifier Source: org_study_id