Evaluation of Efficacy and Safety of PLN-74809 in Patients With Idiopathic Pulmonary Fibrosis

A Randomized, Double-blind, Dose-ranging, Placebo Controlled Phase 2a Evaluation of the Safety, Tolerability and Pharmacokinetics of PLN-74809 in Participants With Idiopathic Pulmonary Fibrosis (INTEGRIS-IPF)

A Phase 2a, multicenter, 4-part, randomized, double-blind, dose-ranging, placebo-controlled study to evaluate the safety, tolerability, and PK of once-daily treatment with PLN-74809 in participants with idiopathic pulmonary fibrosis.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: Placebo; Drug: PLN-74809

Detailed Description

Four part study:

Part A - 4 week treatment period evaluating PLN-74809 or matching placebo

Part B - 12 week treatment period evaluating PLN-74809 or matching placebo

Part C - 12 week treatment period evaluating up to two intermediatery PLN-74809 doses or matching placebo

Part D - ≥ 24 week treatment period evaluating higher PLN-74809 dose or matching placebo

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Royal Prince Alfred Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven
• Canada
  • Ontario
    • Windsor, Ontario, Canada, N8X 5A6
      • Dr. Anil Dhar Medicine Professional Corporation
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie Centre
• Italy
  • Milan, Italy, 20123
    • San Giuseppe Hospital, Multimedica S.p.a.
• Netherlands
  • EJ
    • Eindhoven, EJ, Netherlands, 5623
      • Catharina Ziekenhuis
  • SZ
    • Nijmegen, SZ, Netherlands, 6532
      • Canisius-Wilhelmina Ziekenhuis
• New Zealand
  • Christchurch, New Zealand, 8011
    • University of Otago Christchurch
  • Auckland
    • Greenlane, Auckland, New Zealand, 1051
      • New Zealand Respiratory and Sleep institute
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Pulmonary Associates, PA
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center, Interstitial Lung Disease Program, Pulmonary and Critical Care Medicine
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University Scool of Medicine/ Yale New Haven Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • The Emory Clinic
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Missouri
    • Chesterfield, Missouri, United States, 63017-3625
      • Cardio-Pulmonary Associates of St. Luke's Hospital - Chesterfield
  • North Carolina
    • Greensboro, North Carolina, United States, 27403
      • PulmonIx
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Lung Institute at One Hundred Oaks
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of IPF based upon the Fleischner Society guidelines within 3 years from Screening (Part A) or based on ATS/ERS/JRS/ALAT 2018 guidelines within 5 years from Screening (Part B, C & D)
• FVC % of predicted ≥45%
• DLco (hemoglobin-adjusted) ≥30%
• Participants receiving treatment for IPF with nintedanib or pirfenidone are allowed, if on a stable dose for at least 3 months

Exclusion Criteria:

• Currently receiving or planning to initiate treatment for IPF (fibrosis) with agents not approved for that indication by the FDA
• Forced expiratory volume during the first seconds of the forced breath (FEV1)/FVC ratio <0.7 at Screening
• Clinical evidence of active infection, including but not limited to bronchitis, pneumonia, sinusitis that can affect FVC measurement or IPF progression
• Known acute IPF exacerbation or suspicion by the Investigator of such, within 6 months of Screening
• Smoking of any kind within 3 months of Screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Drug: Placebo; Placebo
Experimental: PLN-74809 Dose Level 1 (Part A); PLN-74809 Dose Level 1 (Part A) - 4 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 Dose Level 2 (Part A); PLN-74809 Dose Level 2 (Part A) - 4 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 Dose Level 2 (Part B); PLN-74809 Dose Level 2 (Part B) - 12 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 - Dose Level 3 (Part C); PLN-74809 Dose Level 3 (Part C) - 12 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 - Dose Level 4 (Part C); PLN-74809 Dose Level 4 (Part C) - 12 weeks	Drug: PLN-74809; PLN-74809
Experimental: PLN-74809 - Dose Level 5 (Part D); PLN-74809 Dose Level 5 (Part D) - ≥ 24 weeks	Drug: PLN-74809; PLN-74809

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Number of Participants With Treatment-Emergent Adverse Events	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 14 days after permanent discontinuation of study drug.	Up to 4 weeks
Part B, C, D - Number of Participants With Treatment-Emergent Adverse Events	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 14 days after permanent discontinuation of study drug.	Up to 12 weeks
Part D - Number of Participants With Treatment-Emergent Adverse Events	An AE was any untoward medical occurrence in a clinical study participant administered a study drug that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and/or unintended sign, symptom, or disease temporally associated with the use of a study drug, whether or not the AE is considered related to the study drug. TEAEs were defined as any AEs with an onset date on or after the study drug start date and no later than 14 days after permanent discontinuation of study drug.	Up to 48 weeks
Part A - Number of Participants With Serious Treatment-Emergent Adverse Events	An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	Up to 4 weeks
Part B, C, D - Number of Participants With Serious Treatment-Emergent Adverse Events	An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	Up to 12 weeks
Part D - Number of Participants With Serious Treatment-Emergent Adverse Events	An SAE was defined as an event that, at any dose, results in the following: death, a life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect or a medically important event or reaction.	Up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A - Assessment of PLN-74809 Total Plasma Concentrations	Part A - Assessment of PLN-74809 Total Plasma Concentrations Week 4, 1 Hour Post Dose	Week 4, 1 Hour Post Dose
Part B, C, D - Assessment of PLN-74809 Total Plasma Concentrations	Part B, C, D - Assessment of PLN-74809 Total Plasma Concentrations Week 12, 2 Hours Post Dose	Week 12, 2 Hours Post Dose
Part D - Assessment of PLN-74809 Total Plasma Concentrations	Part D - Assessment of PLN-74809 Total Plasma Concentrations Week 24, 2 Hours Post Dose	Week 24, 2 Hours Post Dose

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B, C, D - Assessment of Change From Baseline in Forced Vital Capacity (FVC)	Change from Baseline by Visit, Mixed Model for Repeated Measures through Week 12.	Up to 12 weeks
Part D - Assessment of Change From Baseline in Forced Vital Capacity (FVC)	Change from Baseline by Visit, Mixed Model for Repeated Measures through Week 24.	Up to 24 weeks
Part B, C, D - Change in Pulmonary Fibrosis Score by Quantitative HRCT at Week 12	Quantitative Lung Fibrosis extent (%) measures the percentage of lung tissue that is assessed as fibrotic.	Up to 12 weeks
Part D - Change in Pulmonary Fibrosis Score by Quantitative HRCT at Week 24	Quantitative Lung Fibrosis extent (%) measures the percentage of lung tissue that is assessed as fibrotic.	Up to 24 weeks
Part B,C, D - Assessment of Change From Baseline in a Visual Analog Scale (VAS) Scale for Cough	Visual Analog Scale for Cough measures participant reported cough severity on a scale of 0 to 100 with higher scores representative of more severe cough. A negative change from baseline nominally represents reduced cough severity and a positive change from baseline nominally represents increased cough severity.	Up to 12 weeks
Part D - Assessment of Change From Baseline in a Visual Analog Scale (VAS) Scale for Cough	Visual Analog Scale for Cough measures participant reported cough severity on a scale of 0 to 100 with higher scores representative of more severe cough. A negative change from baseline nominally represents reduced cough severity and a positive change from baseline nominally represents increased cough severity.	Up to 24 weeks

Collaborators and Investigators

• Sponsor: Pliant Therapeutics, Inc.
• Investigators: Study Director: Pliant Therapeutics Medical Monitor, Pliant Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2020
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): February 15, 2023

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 21, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: PLN-74809-IPF-202; INTEGRIS-IPF (Other Identifier: Pliant Therapeutics)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No