A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial)

A Phase 2, Multi-Center, Randomized, Double-Blind, Controlled Trial Evaluating the Safety and Efficacy of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial)

The goal of this clinical trial is to evaluate the impact that ENV-101 has on lung function and key measures of fibrosis in adult patients with idiopathic pulmonary fibrosis (IPF). Another goal of this study is to better understand the safety and tolerability of ENV-101 in this patient population.

Study Overview

• Status: Active, not recruiting
• Conditions: Idiopathic Pulmonary Fibrosis; Progressive Fibrosing Interstitial Lung Disease
• Intervention / Treatment: Drug: ENV-101; Drug: Placebo

Detailed Description

This trial is a 6-month, randomized, double-blind, controlled, dose-ranging trial of ENV-101 in adult patients with idiopathic pulmonary fibrosis (IPF). Patients are allowed to continue treatment with approved standard of care (e.g., nintedanib, pirfenidone) during the trial. Patients will be randomized to one of 3 dose levels of ENV-101 or placebo at baseline. The objectives of this trial are to characterize the efficacy, antifibrotic activity, and safety of ENV-101 to select the Phase 3 dose of ENV-101.

• Study Type: Interventional
• Enrollment (Actual): 213
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ABP
    • Research Site
  • Buenos Aires, Argentina, 1888
    • Research Site
  • Mendoza, Argentina, 5501
    • Research Site
  • Mendoza, Argentina, CP 5500
    • Research Site
  • Buenos Aires
    • Quilmes, Buenos Aires, Argentina, B1878FNR
      • Research Site
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Research Site
    • Macquarie Park, New South Wales, Australia, 2109
      • Research Site
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • Research Site
    • South Brisbane, Queensland, Australia, 4101
      • Research Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Research Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Research Site
• Austria
  • Vienna, Austria, 1090
    • Research Site
  • Styria
    • Graz, Styria, Austria, 8036
      • Research Site
• Belgium
  • Brussels, Belgium, 1200
    • Research Site
  • Brussels, Belgium, 1070
    • Research Site
  • Namur
    • Dinant, Namur, Belgium, 5500
      • Research Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2C8
      • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • Research Site
  • Ontario
    • Ajax, Ontario, Canada, L1S 2J5
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Research Site
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Research Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Research Site
• France
  • Angers, France, 49933
    • Research Site
  • Bordeaux, France, 33604
    • Research Site
  • Caen, France, 14033
    • Research Site
  • Dijon, France, 21000
    • Research Site
  • Montpellier, France, 34090
    • Research Site
  • Nantes, France, 44093
    • Research Site
  • Paris, France, 75014
    • Research Site
  • Paris, France, 94270
    • Research Site
  • Rennes, France, 35033
    • Research Site
  • Tours, France, 37044
    • Research Site
• Germany
  • Berlin, Germany, 13125
    • Research Site
  • Leipzig, Germany, 4103
    • Research Site
  • Hesse
    • Giessen, Hesse, Germany, 35398
      • Research Site
    • Immenhausen, Hesse, Germany, 34376
      • Research Site
  • Lower Saxony
    • Hanover, Lower Saxony, Germany, 30625
      • Research Site
  • North Rhine-Westphalia
    • Essen, North Rhine-Westphalia, Germany, 45239
      • Research Site
• Ireland
  • Dublin, Ireland, D04 T6F4
    • Research Site
  • Leinster
    • Dublin, Leinster, Ireland, D05 AT88
      • Research Site
    • Dublin, Leinster, Ireland, D07 A8NN
      • Research Site
  • Munster
    • Cork, Munster, Ireland, T12 DC4A
      • Research Site
• Italy
  • Catania, Italy, 95123
    • Research Site
  • Milan, Italy, 20123
    • Research Site
  • Turin, Italy, 10126
    • Research Site
  • Forli-Cesena
    • Bologna, Forli-Cesena, Italy, 47121
      • Research Site
  • Padua
    • Padua, Padua, Italy, 35128
      • Research Site
  • Tuscany
    • Florence, Tuscany, Italy, 50314
      • Research Site
• Malaysia
  • Selangor
    • Kuala Lumpur, Selangor, Malaysia, 42300
      • Research Site
    • Kuala Lumpur, Selangor, Malaysia, 50590
      • Research Site
    • Kuala Lumpur, Selangor, Malaysia, 56000
      • Research Site
• Mexico
  • Chihuahua City, Mexico, 31230
    • Research Site
  • Mexico City, Mexico, 14080
    • Research Site
  • Oaxaca City, Mexico, 68000
    • Research Site
  • Puebla City, Mexico, 72180
    • Research Site
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64060
      • Research Site
    • Monterrey, Nuevo León, Mexico, 64718
      • Research Site
    • San Nicolás de los Garza, Nuevo León, Mexico, 66465
      • Research Site
  • Querétaro
    • San Juan del Río, Querétaro, Mexico, 76800
      • Research Site
• New Zealand
  • Auckland, New Zealand
    • Research Site
  • Christchurch, New Zealand, 8011
    • Research Site
  • Hamilton, New Zealand
    • Research Site
• South Korea
  • Seoul, South Korea, 16499
    • Research Site
  • (Deogyang District)
    • Seoul, (Deogyang District), South Korea, 10475
      • Research Site
  • (Dong District)
    • Ulsan, (Dong District), South Korea, 44033
      • Research Site
  • (Haeundae District)
    • Busan, (Haeundae District), South Korea, 48108
      • Research Site
  • (Seongbuk District)
    • Seoul, (Seongbuk District), South Korea, 02841
      • Research Site
  • (Songpa District)
    • Seoul, (Songpa District), South Korea, 05505
      • Research Site
  • (Yongsan District)
    • Seoul, (Yongsan District), South Korea, 04401
      • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Research Site
  • Birmingham, United Kingdom, B9 5SS
    • Research Site
  • Birmingham, United Kingdom, B15 2GW
    • Research Site
  • Cambridge, United Kingdom, CB2 0AY
    • Research Site
  • Edinburgh, United Kingdom, EH1 3EG
    • Research Site
  • Exeter, United Kingdom, EX2 5DW
    • Research Site
  • Leicester, United Kingdom, LE3 9QP
    • Research Site
  • London, United Kingdom, SW3 6NP
    • Research Site
  • Londonderry, United Kingdom, BT47 6SB
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 40 years old with an IPF diagnosis as confirmed by the Investigator.
• Percent predicted FVC of ≥ 45% at study start.
• Percent predicted diffusing capacity of lung for carbon monoxide (DLCO) ≥ 25%, adjusted for hemoglobin (Hgb) at study start.
• Ability to perform spirometry tests.
• Either stable treatment with standard of care (SoC) [i.e., antifibrotics, immunosuppressants (PPF only)] for at least 3 months prior to study start or not treated with SoC for at least 8 weeks prior to study start.

Exclusion Criteria:

• Evidence of other known causes of interstitial lung disease (ILD).
• Forced expiratory volume in one second (FEV1)/FVC ratio <0.7 at study start.

• History of malignancy, including carcinoma during the preceding 5 years from study start, with the following exceptions:

  1. Prior history of in situ melanoma, basal or squamous cell skin cancer if treated with curative therapy.
  2. Patients with prostate cancer that are managed by surveillance.
  3. Patients with ductal carcinoma in situ, treated surgically with curative intent.
• Patients with moderate to severe hepatic impairment (Child-Pugh B and C).
• Smoking (including vaping) within 6 months of study start; current smoker, or unwillingness to refrain from smoking during the clinical trial duration.
• Active or suspected alcohol or drug abuse in the opinion of the Investigator.
• Currently enrolled in another investigational device or drug trial, or less than 3 months from study start since ending another investigational device or drug trial(s) or receiving other investigational treatment(s).
• Presence of active infection at study start or confirmed active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
• Major surgery requiring hospitalization (according to the Investigator) performed within 3 months prior to study start or planned during the course of the trial. Being on a transplant list is allowed.
• Occurrence of serious illness requiring hospitalization within 90 days prior to study start.

• Current or previous use (within 28 days prior to study start) of the following:

  1. Endothelin receptor antagonist
  2. Riociguat
  3. Prostacyclin or prostacyclin analogue
  4. Radiation to the lungs
  5. Oral corticosteroids >15 mg/day
• Use of cyclophosphamide or tocilizumab within 8 weeks, or rituximab within 6 months, prior to study start.
• Use of drugs that are known moderate or stronger CYP3A4 inhibitors or inducers within 14 days prior to study start. Patients must also agree not to eat fruits that inhibit CYP3A4 such as grapefruit, Seville oranges, pomelo and star fruit.
• Patients of reproductive potential who are sexually active and unwilling to use birth control for the duration of the study and for 3 months after their final dose of study drug.
• Females that are pregnant or nursing.
• Patients that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final dose of study drug.
• Males who are unwilling to refrain from sperm donation and females who are unwilling to refrain from egg donation for the duration of the study and for 3 months after their final dose of study drug.
• Patients with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of ENV-101.
• Patients who have previously taken ENV-101.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ENV-101 Low Dose (IPF Population)	Drug: ENV-101; oral tablet, dosed once a day; Other Names: taladegib
Experimental: ENV-101 Mid Dose (IPF Population)	Drug: ENV-101; oral tablet, dosed once a day; Other Names: taladegib
Experimental: ENV-101 High Dose (IPF Population)	Drug: ENV-101; oral tablet, dosed once a day; Other Names: taladegib
Placebo Comparator: Placebo (IPF Population)	Drug: Placebo; oral tablet, dosed once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in percent predicted forced vital capacity (ppFVC) compared to placebo	ppFVC is a measure of lung function	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Absolute change in FVC (mL) compared to placebo	FVC is a measure of lung function	Baseline and Week 24
Time to disease progression (absolute decline in ppFVC >10%, IPF-related hospitalization, or death) compared to placebo		Baseline and Week 24
Absolute change in the Living with Pulmonary Fibrosis Symptoms (L-PF Symptoms) Questionnaire Cough domain score compared to placebo	The L-PF Symptoms Questionnaire Cough domain consists of 6 questions regarding a subject's experience with cough over the prior 24 hours. Questions have response options on a five-point numeric rating scale with an anchor of 0 ("Not at all") to 4 ("Extremely"). Total score for the Cough domain is normalized to the range 0 to 100, with higher scores indicating greater impairment.	Baseline and Week 24
Absolute change in the L-PF Symptoms Questionnaire Dyspnea domain score compared to placebo	The L-PF Symptoms Questionnaire Dyspnea domain consists of 12 questions regarding a subject's experience with dyspnea (shortness of breath) over the prior 24 hours. Questions have response options on a five-point numeric rating scale with an anchor of 0 ("Not at all") to 4 ("Extremely"). Total score for the Dyspnea domain is normalized to the range 0 to 100, with higher scores indicating greater impairment.	Baseline and Week 24
Absolute change in the L-PF Symptoms Questionnaire Fatigue domain score compared to placebo	The L-PF Symptoms Questionnaire Fatigue domain consists of 5 questions regarding a subject's experience with fatigue over the prior 24 hours. Questions have response options on a five-point numeric rating scale with an anchor of 0 ("Not at all") to 4 ("Extremely"). Total score for the Fatigue domain is normalized to the range 0 to 100, with higher scores indicating greater impairment.	Baseline and Week 24
Absolute change in total lung capacity (TLC) by chest high-resolution computed tomography (HRCT) imaging compared to placebo	HRCT is a method of imaging which is more precise than chest x-ray in the diagnosis and monitoring of diseases of the lung tissue and the airways.	Baseline and Week 24
Absolute change in % quantitative interstitial lung disease (QILD) by chest HRCT imaging compared to placebo compared to placebo		Baseline and Week 24
Absolute change in % quantitative ground glass opacity (QGG) by chest HRCT imaging compared to placebo		Baseline and Week 24
Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo		Baseline and Week 24
Absolute change in the L-PF Symptoms module score compared to placebo	The L-PF Symptoms module is a 23-item patient-reported outcome measure designed to assess the severity of dyspnea (12 items), cough (6 items), and fatigue (5 items) experienced by a subject over the prior 24 hours. Questions have response options on a five-point numeric rating scale with an anchor of 0 ("Not at all") to 4 ("Extremely"). Total score for the Symptoms module is normalized to the range 0 to 100, with higher scores indicating greater impairment.	Baseline and Week 24
Absolute change in the L-PF Impacts module score compared to placebo	The L-PF Impacts module consists of 21 questions regarding a subject's experience with the impacts of pulmonary fibrosis on daily life over the prior week. Questions have response options on a five-point numeric rating scale with an anchor of 0 ("Not at all") to 4 ("Extremely"). Total score for the Impacts module domain is normalized to the range 0 to 100, with higher scores indicating greater impairment.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Endeavor Biomedicines, Inc.
• Investigators: Study Director: Lisa Lancaster, M.D., Endeavor Biomedicines

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: May 15, 2024
• First Submitted That Met QC Criteria: May 15, 2024
• First Posted (Actual): May 21, 2024

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 20, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: hedgehog pathway inhibitor; pulmonary fibrosis; taladegib
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pathological Conditions, Signs and Symptoms; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Substandard Drugs; Pharmaceutical Preparations; LY2940680
• Other Study ID Numbers: ENV-IPF-103

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
• product manufactured in and exported from the U.S.: Yes