Evaluation of Efficacy and Safety of Pamrevlumab in Patients With Idiopathic Pulmonary Fibrosis

• ClinicalTrials.gov Identifier: NCT03955146
• Recruitment Status: Recruiting
• First Posted: May 17, 2019
• Last Update Posted: January 29, 2021
• Sponsor: FibroGen
• Information provided by (Responsible Party): FibroGen

Tracking Information

• First Submitted Date: May 16, 2019
• First Posted Date: May 17, 2019
• Last Update Posted Date: January 29, 2021
• Actual Study Start Date: June 27, 2019
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 20, 2020): Change in FVC (L) [ Time Frame: Baseline to Week 48 ]
• Original Primary Outcome Measures (submitted: May 16, 2019): Change in FVC (L) [ Time Frame: Baseline to Week 52 ]

Current Secondary Outcome Measures (submitted: November 20, 2020)

• Time to disease progression defined as absolute FVCpp decline of ≥10% or death, whichever occurs first. [ Time Frame: Baseline to Week 48 ]
• Change in FVCpp (absolute and relative) [ Time Frame: Baseline to Week 48 ]
• Time to composite of clinical outcomes: respiratory hospitalization or death or absolute FVCpp decline ≥10%, whichever occurs first [ Time Frame: Baseline to Week 48 ]
• Time to first respiratory hospitalizations during study [ Time Frame: Baseline to Week 48 ]
• Change in Quantitative Lung Fibrosis (QLF) volume [ Time Frame: Baseline to Week 48 ]
• Change in St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline to Week 48 ]
  The SGRQ is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status.
• Change in University of California San Diego - Shortness of Breath Questionnaire (UCSD-SOBQ) [ Time Frame: Baseline to Week 48 ]
  The UCSD SOBQ is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).
• Change in Leicester Cough Questionnaire (LCQ) [ Time Frame: Baseline to Week 48 ]
  The LCQ is a self-reporting quality of life measure of chronic cough. It consists of 19 items with a 7 point likert response scale (range from 1 to 7). Each item is developed to assess symptoms during cough and impact of cough on three main domains: physical, psychological and social. Scores are calculated as a mean of each domain and the total score is calculated by adding every domain score.
• Time to all-cause mortality during study [ Time Frame: Baseline to Week 48 ]
• Time to first acute IPF exacerbations during study [ Time Frame: Baseline to Week 48 ]

Original Secondary Outcome Measures (submitted: May 16, 2019)

• Change in FVC percent predicted (FVCpp) [ Time Frame: Baseline to Week 52 ]
• Subjects with FVCpp decline of 10% or more or death during study [ Time Frame: Baseline to Week 52 ]
• Composite clinical outcomes including the following: respiratory hospitalization + death + acute IPF exacerbations + FVCpp decline ≥10% [ Time Frame: Baseline to Week 52 ]
• Change in St. George's Respiratory Questionnaire (SGRQ) score [ Time Frame: Baseline to Week 52 ]
  The St. George's Respiratory Questionnaire (SGRQ) is a 50-item questionnaire developed to measure health status (quality of life). Scores are calculated for three domains: Symptoms, Activity and Impacts. The total score (summed weights) can range from 0 to 100 with a lower score denoting a better health status.
• Change in QLF volume [ Time Frame: Baseline to Week 52 ]
• Change in University of California San Diego - Shortness of Breath Questionnaire (UCSD-SOBQ) [ Time Frame: Baseline to Week 52 ]
  The University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ) is a 24-item questionnaire developed to measure breathlessness associated with activities of daily living, on a scale between zero and five where 0 is not at all breathless and 5 is maximally breathless or too breathless to do the activity. The responses to all items are summed up to provide the overall score that can range from 0 (best outcome) to 120 (worst outcome).
• Mortality rate [ Time Frame: Baseline to Week 52 ]
• Acute IPF exacerbations [ Time Frame: Baseline to Week 52 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Efficacy and Safety of Pamrevlumab in Patients With Idiopathic Pulmonary Fibrosis
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Brief Summary: This is a Phase 3 trial to evaluate the efficacy and safety of 30 mg/kg intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in subjects with Idiopathic Pulmonary Fibrosis

Detailed Description

This is a Phase 3, randomized, double-blind, placebo-controlled, multi-center trial to evaluate the efficacy and safety of pamrevlumab in subjects with idiopathic pulmonary fibrosis (IPF).

Subjects who are not being treated with approved IPF therapies (i.e., nintedanib or pirfenidone) may be eligible for screening. Examples of reasons subjects 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
• Subject voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks

NOTE: No subject should discontinue an approved IPF therapy for the purpose of enrolling in this study.

Approximately 340 eligible subjects will be randomized at a 1:1 ratio to Arm A or Arm B, respectively:

Arm A: pamrevlumab, 30 mg/kg IV, Day 1 and every 3 weeks thereafter

Arm B: Matching placebo IV, Day 1 and every 3 weeks thereafter

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 subject 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 (i.e., 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.

Subjects who discontinue study treatment for any reason should be encouraged to remain in the study and be followed for all study visits and assessments.

Subjects who complete the study will be eligible for an open-label, extension with pamrevlumab.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

• Drug: Pamrevlumab
  Pamrevlumab: 30 mg/kg by intravenous infusion every 3 weeks for a total of 17 infusions over 48 weeks
  Other Name: FG-3019
• Drug: Placebo
  Placebo: 30 mg/kg by intravenous infusion every 3 weeks for a total of 17 infusions over 48 weeks

Study Arms

• Experimental: Pamrevlumab
  Intervention: Drug: Pamrevlumab
• Experimental: Placebo
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 1, 2020): 340
• Original Estimated Enrollment (submitted: May 16, 2019): 565
• Estimated Study Completion Date: January 2023
• Estimated Primary Completion Date: December 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Diagnosis of IPF as defined by ATS/ERS/JRS/ALAT guidelines (Raghu 2018) within the past 7 years prior to study participation.
2. HRCT scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
3. FVCpp value >45% and <95%
4. Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90% at screening (determined locally).
5. Not currently receiving treatment for IPF with an approved therapy (i.e., pirfenidone or nintedanib) for any reason, including prior intolerance to an approved IPF therapy.

Key Exclusion Criteria:

1. Previous exposure to pamrevlumab.
2. Evidence of significant obstructive lung disease.
3. Female subjects 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.
7. Other types of respiratory diseases including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
8. Certain medical conditions, including recent (e.g. MI/stroke, or severe chronic heart failure or pulmonary hypertension, or cancers.
9. Acute IPF exacerbation during Screening or Randomization.
10. Recent use of any investigational drugs or unapproved therapies, or approved or participation in any clinical trial.
11. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gustavo Lorente; 650-273-2264; Zephyrus@Fibrogen.com

• Listed Location Countries: Argentina, Australia, Chile, Hong Kong, Korea, Republic of, Taiwan, United States

Administrative Information

• NCT Number: NCT03955146
• Other Study ID Numbers: FGCL-3019-091
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: FibroGen
• Study Sponsor: FibroGen
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: FibroGen
• Verification Date: January 2021