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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
Information provided by (Responsible Party):
FibroGen

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.

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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


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




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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01890265


Locations
Show Show 42 study locations
Sponsors and Collaborators
FibroGen
Investigators
Layout table for investigator information
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

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: FibroGen
ClinicalTrials.gov Identifier: NCT01890265    
Other Study ID Numbers: FGCL-3019-067
First Posted: July 1, 2013    Key Record Dates
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:
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Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Pirfenidone
Nintedanib
Immunoglobulins
Antibodies
Immunoglobulin G
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
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