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

A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients With Idiopathic Pulmonary Fibrosis

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.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: Pamrevlumab; Drug: Sub-Study: Pirfenidone; Drug: Sub-Study: Nintedanib

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation
  • South Australia
    • Adelaide, South Australia, Australia, 5041
      • Daw Park Repatriation
• Bulgaria
  • Sofia, Bulgaria, 1407
    • MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology
• Canada
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Université de Sherbrooke / Hôpital Charles LeMoyne
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560034
      • St Johns Medical College Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400007
      • Bhatia Hospital
  • Tamil Nadu
    • Coimbatore, Tamil Nadu, India, 641045
      • Sri Bala Medical Centre and Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226006
      • Midland Healthcare & Research Center
  • West Bengal
    • Kolkata, West Bengal, India, 700107
      • Fortis Hospitals
• New Zealand
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital NZ
  • Dunedin, New Zealand, 9016
    • Dunedin Public Hospital
  • Hamilton, New Zealand, 3204
    • Waikato Hospital
  • Tauranga, New Zealand, 3143
    • Tauranga Hospital
• South Africa
  • Gauteng
    • Pretoria, Gauteng, South Africa, 0181
      • Into Research
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4068
      • Life Mount Edgecombe Hospital
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7505
      • Tygerberg Hospital Respiratory Research Unit
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • The Kirklin Clinic
  • California
    • Los Angeles, California, United States, 90024
      • David Geffen School of Medicine at UCLA
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center
  • Colorado
    • Denver, Colorado, United States, 80206
      • National Jewish Health
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Florida
    • Kissimmee, Florida, United States, 34741
      • Pulmonary Disease Specialist, PA
    • Pensacola, Florida, United States, 32504
      • Pensacola Research Consultants, Inc., d.b.a. Avanza Medical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
    • Wichita, Kansas, United States, 67208
      • Via Christi Clinic, P.A.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02135
      • Steward St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Medical Center
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • St. Luke's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • PulmonIx LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cinncinati
    • Lebanon, Ohio, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Legacy Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5735
      • Vanderbilt University
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah - Lung Health Research
  • Vermont
    • Colchester, Vermont, United States, 05446
      • Vermont Lung Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Pamrevlumab; Solution for infusion; Other Names: FG-3019; Fully human recombinant immunoglobulin G (IgG), kappa monoclonal anti-body.
Placebo Comparator: Placebo; Participants will receive placebo matching pamrevlumab by IV infusion every 3 weeks for a total of 16 infusions over 45 weeks.	Drug: Placebo; Solution for infusion
Active Comparator: 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.	Drug: Pamrevlumab; Solution for infusion; Other Names: FG-3019; Fully human recombinant immunoglobulin G (IgG), kappa monoclonal anti-body.; Drug: Sub-Study: Pirfenidone; Pirfenidone concomitant therapy will not be provided by the Sponsor.; Other Names: Esbeiet; Drug: Sub-Study: Nintedanib; Nintedanib concomitant therapy will not be provided by the Sponsor.; Other Names: Ofev
Placebo Comparator: 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.	Drug: Placebo; Solution for infusion; Drug: Sub-Study: Pirfenidone; Pirfenidone concomitant therapy will not be provided by the Sponsor.; Other Names: Esbeiet; Drug: Sub-Study: Nintedanib; Nintedanib concomitant therapy will not be provided by the Sponsor.; Other Names: Ofev

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48	FVC in liters was measured during the spirometry assessments at screening and during the randomized treatment period at Day 1 and every 12 weeks. The FVC (% predicted) was calculated for the corresponding gender-race-age group. The least squares (LS) mean change from Baseline to Week 48 (end of the randomized treatment period) in FVC (% predicted) is presented. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Other statistical analysis data is reported in the statistical analysis section. Observed data from all visits were included in the model.	Baseline (Screening and Day 1), Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48	The extent of pulmonary fibrosis was measured by HRCT scans of the chest at screening and at Weeks 24 and 48, to determine the HRCT QLF score. Each lung was divided into 5 lobes (right upper, right middle, right lower, left upper, left lower). For the quantitative HRCT analyses, a computer read the images and quantified the percent (%) and volume (mL) of fibrosis for the whole lung by averaging the scores from each of 5 lung lobes. Baseline was defined as the Screening evaluation. Missing data were imputed using the multiple imputation (MI) method to handle missing values.	Baseline (Screening), Week 24 and Week 48
Number of Participants With IPF Progression Events up to Week 48	IPF progression events included death from any cause or absolute decline in FVC (% predicted) value of ≥10%, confirmed by repeat spirometry. Classification of FVC (% predicted) declined ≥10% was based on observed and imputed data. Missing data in FVC (% predicted) were imputed using the predicted values from the random coefficient module with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope as random effect.	Baseline (Screening and Day 1) up to Week 48
Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48	HRQoL was assessed by the SGRQ to measure health impairment, and includes 17 questions in 3 domains: Symptoms, Activity and Impacts. The domain and total scores range from 0 to 100, with 0 indicating the best and 100 indicating the worst possible health status. Missing data at post-baseline visits were imputed as the predicted values from the random coefficient model which included treatment, visit, visit-by-treatment interaction, and Baseline SGRQ score as fixed effects and linear slope of visit as random effect.	Baseline (Day 1), Week 24 and Week 48
Number of Participants With a Respiratory-Related Hospitalization	Respiratory-related hospitalizations were reported by participants and recorded by the Investigators.	Week 55
Number of Participants With a Respiratory-Related Death	Investigators determined whether a death was respiratory-related.	Week 55
Number of Participants With No Decline in FVC (% Predicted) at Week 48	FVC in liters was measured during the spirometry assessments. The FVC (% predicted) was calculated for the corresponding gender-race-age group. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Classification of 'No decline' is based on observed and imputed data. Missing data in FVC (% predicted) are imputed using the predicted values from the random coefficient model with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope of visit as random effect.	Baseline (Day 1) to Week 48.

Collaborators and Investigators

• Sponsor: FibroGen
• Investigators: Principal Investigator: Mark Wencel, M.D, Via Christi Clinic, P.A., USA; Principal Investigator: Joao de Andrade, M.D, The Kirklin Clinic, USA; Principal Investigator: Peter LaCamera, M.D., Steward St. Elizabeth's Medical Center, USA; Principal Investigator: Danielle Antin-Ozerkis, M.D., Yale University, USA; Principal Investigator: Rishi Raj, M.D., Northwestern University; Principal Investigator: Neil Ettinger, M.D, St Luke's Hospital, USA; Principal Investigator: Rafael Perez, M.D, University of Louisville, USA; Principal Investigator: Timothy Albertson, M.D, University of California Davis Medical Center, USA; Principal Investigator: Yolanda Mageto, M.D., Vermont Lung Center, USA; Principal Investigator: Srihari Veeraraghavan, M.D, Emory University, USA; Principal Investigator: Nishant Gupta, M.D, University of Cinncinati, USA; Principal Investigator: Kevin Gibson, M.D, University of Pittsburgh Medical Center, USA; Principal Investigator: Lisa Lancaster, M.D., Vanderbilt University, USA; Principal Investigator: Mary Beth Scholand, M.D., University of Utah - Lung Health Research, USA; Principal Investigator: Mark Hamblin, M.D., University of Kansas Medical Center, USA; Principal Investigator: John Fitzgerald, M.D., University of Texas Southwestern Medical Center, USA; Principal Investigator: John Belperio, M.D., David Geffen School of Medicine at UCLA, USA; Principal Investigator: Richard Enelow, M.D., Dartmouth-Hitchcock Medical Center, USA; Principal Investigator: Evans R Fernandez-Perez, M.D, National Jewish Center, USA; Principal Investigator: Peter A Bercz, M.D, Pensacola Research Consultants, INC., USA; Principal Investigator: Krishna Thavarajah, M.D., Henry Ford Medical Center, USA; Principal Investigator: James Britt, M.D., University of Maryland, College Park; Principal Investigator: Danielle D. Hosmer, Legacy Research Institute, USA; Principal Investigator: David Lederer, M.D., Columbia University Medical Center, USA; Principal Investigator: Murali Ramaswamy, M.D., PulmonIx LLC, USA; Principal Investigator: Thomas O'Brien, M.D., Pulmonary Disease Specialist, PA, USA; Principal Investigator: Nadim Srour, M.D., Université de Sherbrooke / Hôpital Charles LeMoyne, Canada; Principal Investigator: Elvis Irusen, M.D., Tygerberg Hospital Respiratory Research Unit, South Africa; Principal Investigator: Anish Ambaram, M.D., Life Mount Edgecombe Hospital, South Africa; Principal Investigator: Heidi Siebert, M.D., Into Research, South Africa; Principal Investigator: Elizabeth Veitch, M.D., Concord Repatriation, Australia; Principal Investigator: Huw Davies, M.D., Daw Park Repatriation, Australia; Principal Investigator: Lutz Beckert, M.D., Christchurch Hospital NZ, New Zealand; Principal Investigator: Catherina Chang, M.D., Waikato Hospital, New Zealand; Principal Investigator: Benedict Brockway, M.D., Dunedin Public Hospital, New Zealand; Principal Investigator: Suzanne Poole, M.D., Tauranga Hospital, New Zealand; Principal Investigator: Raja Dhar, M.D., Fortis Hospitals, India; Principal Investigator: Bhanu Singh, M.D., Midland Healthcare & Research Center, India; Principal Investigator: Nandagopal Velayuthaswamy, M.D., Sri Bala Medical Centre and Hospital, India; Principal Investigator: Sujeet Rajan, M.D., Bhatia Hospital, India; Principal Investigator: Priya Ramachandran, M.D., St Johns Medical College Hospital, India; Principal Investigator: Natalia Stoeva, M.D., MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology, Bulgaria

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 30, 2013
• Primary Completion (Actual): November 16, 2017
• Study Completion (Actual): November 16, 2017

Study Registration Dates

• First Submitted: June 24, 2013
• First Submitted That Met QC Criteria: June 27, 2013
• First Posted (Estimate): July 1, 2013

Study Record Updates

• Last Update Posted (Actual): September 4, 2020
• Last Update Submitted That Met QC Criteria: August 19, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Idiopathic Pulmonary Fibrosis; IPF; Interstitial Lung Disease; Idiopathic Interstitial Pneumonia; Lung Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Protein Kinase Inhibitors; Antibodies; Immunoglobulins; Pirfenidone; Nintedanib; Antibodies, Monoclonal; Immunoglobulin G
• Other Study ID Numbers: FGCL-3019-067