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

• ClinicalTrials.gov Identifier: NCT01890265
• Recruitment Status: Completed
• First Posted: July 1, 2013
• Results First Posted: September 4, 2020
• Last Update Posted: September 4, 2020
• Sponsor: FibroGen
• Information provided by (Responsible Party): FibroGen

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Pamrevlumab; Drug: Placebo; Drug: Sub-Study: Pirfenidone; Drug: Sub-Study: Nintedanib	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Participants, Investigators, and study staff were blinded to treatment assignments and did not have access to the randomization codes. The high-resolution computed tomography (HRCT) readers were blinded to treatment assignments.
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients With Idiopathic Pulmonary Fibrosis
• Actual Study Start Date: July 30, 2013
• Actual Primary Completion Date: November 16, 2017
• Actual Study Completion Date: November 16, 2017

Arms and Interventions

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: Fully human recombinant immunoglobulin G (IgG), kappa monoclonal anti-body.; FG-3019
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: Fully human recombinant immunoglobulin G (IgG), kappa monoclonal anti-body.; FG-3019; Drug: Sub-Study: Pirfenidone; Pirfenidone concomitant therapy will not be provided by the Sponsor.; Other Name: Esbeiet; Drug: Sub-Study: Nintedanib; Nintedanib concomitant therapy will not be provided by the Sponsor.; Other Name: 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 Name: Esbeiet; Drug: Sub-Study: Nintedanib; Nintedanib concomitant therapy will not be provided by the Sponsor.; Other Name: Ofev

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48 [ Time Frame: Baseline (Screening and Day 1), 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.

Secondary Outcome Measures :

1. Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48 [ Time Frame: Baseline (Screening), 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.
2. Number of Participants With IPF Progression Events up to Week 48 [ Time Frame: Baseline (Screening and Day 1) 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.
3. 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 [ Time Frame: Baseline (Day 1), 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.
4. Number of Participants With a Respiratory-Related Hospitalization [ Time Frame: Week 55 ]
   Respiratory-related hospitalizations were reported by participants and recorded by the Investigators.
5. Number of Participants With a Respiratory-Related Death [ Time Frame: Week 55 ]
   Investigators determined whether a death was respiratory-related.
6. Number of Participants With No Decline in FVC (% Predicted) at Week 48 [ Time Frame: Baseline (Day 1) to 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.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

The Kirklin Clinic

Birmingham, Alabama, United States, 35294

United States, California

David Geffen School of Medicine at UCLA

Los Angeles, California, United States, 90024

UC Davis Medical Center

Sacramento, California, United States, 95817

United States, Colorado

National Jewish Health

Denver, Colorado, United States, 80206

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06520

United States, Florida

Pulmonary Disease Specialist, PA

Kissimmee, Florida, United States, 34741

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

Pensacola, Florida, United States, 32504

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

United States, Illinois

Northwestern University

Chicago, Illinois, United States, 60611

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Via Christi Clinic, P.A.

Wichita, Kansas, United States, 67208

United States, Kentucky

University of Louisville

Louisville, Kentucky, United States, 40202

United States, Maryland

University of Maryland

Baltimore, Maryland, United States, 21201

United States, Massachusetts

Steward St. Elizabeth's Medical Center

Boston, Massachusetts, United States, 02135

United States, Michigan

Henry Ford Medical Center

Detroit, Michigan, United States, 48202

United States, Missouri

St. Luke's Hospital

Chesterfield, Missouri, United States, 63017

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, North Carolina

PulmonIx LLC

Greensboro, North Carolina, United States, 27403

United States, Ohio

University of Cinncinati

Cincinnati, Ohio, United States, 45267

Dartmouth-Hitchcock Medical Center

Lebanon, Ohio, United States, 03756

United States, Oregon

Legacy Research Institute

Portland, Oregon, United States, 97210

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37232-5735

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

United States, Utah

University of Utah - Lung Health Research

Salt Lake City, Utah, United States, 84108

United States, Vermont

Vermont Lung Center

Colchester, Vermont, United States, 05446

Australia, New South Wales

Concord Repatriation

Concord, New South Wales, Australia, 2139

Australia, South Australia

Daw Park Repatriation

Adelaide, South Australia, Australia, 5041

Bulgaria

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

Sofia, Bulgaria, 1407

Canada, Quebec

Université de Sherbrooke / Hôpital Charles LeMoyne

Greenfield Park, Quebec, Canada, J4V 2H1

India

St Johns Medical College Hospital

Bangalore, Karnataka, India, 560034

Bhatia Hospital

Mumbai, Maharashtra, India, 400007

Sri Bala Medical Centre and Hospital

Coimbatore, Tamil Nadu, India, 641045

Midland Healthcare & Research Center

Lucknow, Uttar Pradesh, India, 226006

Fortis Hospitals

Kolkata, West Bengal, India, 700107

New Zealand

Christchurch Hospital NZ

Christchurch, New Zealand, 8011

Dunedin Public Hospital

Dunedin, New Zealand, 9016

Waikato Hospital

Hamilton, New Zealand, 3204

Tauranga Hospital

Tauranga, New Zealand, 3143

South Africa

Into Research

Pretoria, Gauteng, South Africa, 0181

Life Mount Edgecombe Hospital

Durban, KwaZulu-Natal, South Africa, 4068

Tygerberg Hospital Respiratory Research Unit

Cape Town, Western Cape, South Africa, 7505

Sponsors and Collaborators

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

  Study Documents (Full-Text)

Documents provided by FibroGen:

Study Protocol  [PDF] December 12, 2016

Statistical Analysis Plan: Part 1  [PDF] July 26, 2017

Statistical Analysis Plan: Part 2  [PDF] March 14, 2018

More Information

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: FibroGen
• ClinicalTrials.gov Identifier: NCT01890265
• Other Study ID Numbers: FGCL-3019-067
• First Posted: July 1, 2013
• Results First Posted: September 4, 2020
• Last Update Posted: September 4, 2020
• Last Verified: August 2020

Keywords provided by FibroGen:

Idiopathic Pulmonary Fibrosis; IPF; Idiopathic Interstitial Pneumonia; Interstitial Lung Disease; Lung Fibrosis

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Pirfenidone; Nintedanib; Immunoglobulins; Antibodies; Immunoglobulin G; Antibodies, Monoclonal; Immunologic Factors; Physiological Effects of Drugs; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents