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

NCT06422884 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: ENV-IPF-103
• Study Type: interventional
• Target: 213
• Locations: 13 countries
• Sites: 76

Brief Summary

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.

Conditions

Idiopathic Pulmonary Fibrosis; Progressive Fibrosing Interstitial Lung Disease

Keywords

taladegib; hedgehog pathway inhibitor; pulmonary fibrosis

Outcome Measures

Primary Outcomes (1)

• Change in percent predicted forced vital capacity (ppFVC) compared to placebo

  ppFVC is a measure of lung function

  Baseline and Week 24

Secondary Outcomes (11)

• Absolute change in FVC (mL) compared to placebo

  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

  Baseline and Week 24

• Absolute change in the L-PF Symptoms Questionnaire Dyspnea domain score compared to placebo

  Baseline and Week 24

• Absolute change in the L-PF Symptoms Questionnaire Fatigue domain score compared to placebo

  Baseline and Week 24

Study Arms (4)

ENV-101 Low Dose (IPF Population)

EXPERIMENTAL

Drug: ENV-101

ENV-101 Mid Dose (IPF Population)

EXPERIMENTAL

Drug: ENV-101

ENV-101 High Dose (IPF Population)

EXPERIMENTAL

Drug: ENV-101

Placebo (IPF Population)

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ENV-101 DRUG

oral tablet, dosed once a day

Also known as: taladegib

ENV-101 High Dose (IPF Population); ENV-101 Low Dose (IPF Population); ENV-101 Mid Dose (IPF Population)

Placebo DRUG

oral tablet, dosed once a day

Placebo (IPF Population)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Prior history of in situ melanoma, basal or squamous cell skin cancer if treated with curative therapy.
• Patients with prostate cancer that are managed by surveillance.
• 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:
• Endothelin receptor antagonist

Sponsors & Collaborators

• Endeavor Biomedicines, Inc.: lead

Study Sites (78)

Research Site

Quilmes, Buenos Aires, B1878FNR, Argentina

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Buenos Aires, 1888, Argentina

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Buenos Aires, C1426ABP, Argentina

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Mendoza, 5501, Argentina

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Mendoza, CP 5500, Argentina

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Camperdown, New South Wales, 2050, Australia

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Macquarie Park, New South Wales, 2109, Australia

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Brisbane, Queensland, 4032, Australia

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South Brisbane, Queensland, 4101, Australia

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Box Hill, Victoria, 3128, Australia

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Nedlands, Western Australia, 6009, Australia

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Graz, Styria, 8036, Austria

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Vienna, 1090, Austria

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Dinant, Namur, 5500, Belgium

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Edmonton, Alberta, T6G 2C8, Canada

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Vancouver, British Columbia, V6Z 2K5, Canada

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Ajax, Ontario, L1S 2J5, Canada

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Montreal, Quebec, H2X 0A9, Canada

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Sherbrooke, Quebec, J1H 5N4, Canada

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Trois-Rivières, Quebec, G8T 7A1, Canada

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Angers, 49933, France

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Bordeaux, 33604, France

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Caen, 14033, France

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Dijon, 21000, France

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Montpellier, 34090, France

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Nantes, 44093, France

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Paris, 75014, France

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Paris, 94270, France

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Rennes, 35033, France

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Tours, 37044, France

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Giessen, Hesse, 35398, Germany

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Immenhausen, Hesse, 34376, Germany

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Hanover, Lower Saxony, 30625, Germany

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Essen, North Rhine-Westphalia, 45239, Germany

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Berlin, 13125, Germany

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Leipzig, 4103, Germany

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Dublin, Leinster, D05 AT88, Ireland

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Dublin, Leinster, D07 A8NN, Ireland

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Cork, Munster, T12 DC4A, Ireland

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Dublin, D04 T6F4, Ireland

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Bologna, Forli-Cesena, 47121, Italy

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Padua, Padua, 35128, Italy

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Florence, Tuscany, 50314, Italy

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Catania, 95123, Italy

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Milan, 20123, Italy

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Turin, 10126, Italy

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Kuala Lumpur, Selangor, 42300, Malaysia

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Kuala Lumpur, Selangor, 50590, Malaysia

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Kuala Lumpur, Selangor, 56000, Malaysia

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Monterrey, Nuevo León, 64060, Mexico

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Monterrey, Nuevo León, 64718, Mexico

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San Nicolás de los Garza, Nuevo León, 66465, Mexico

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San Juan del Río, Querétaro, 76800, Mexico

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Chihuahua City, 31230, Mexico

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Mexico City, 14080, Mexico

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Oaxaca City, 68000, Mexico

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Puebla City, 72180, Mexico

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Auckland, New Zealand

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Christchurch, 8011, New Zealand

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Hamilton, New Zealand

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Seoul, (Deogyang District), 10475, South Korea

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Ulsan, (Dong District), 44033, South Korea

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Busan, (Haeundae District), 48108, South Korea

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Seoul, (Seongbuk District), 02841, South Korea

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Seoul, (Songpa District), 05505, South Korea

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Seoul, (Yongsan District), 04401, South Korea

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Seoul, 16499, South Korea

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Belfast, BT9 7AB, United Kingdom

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Birmingham, B15 2GW, United Kingdom

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Birmingham, B9 5SS, United Kingdom

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Cambridge, CB2 0AY, United Kingdom

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Edinburgh, EH1 3EG, United Kingdom

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Exeter, EX2 5DW, United Kingdom

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Leicester, LE3 9QP, United Kingdom

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London, SW3 6NP, United Kingdom

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Londonderry, BT47 6SB, United Kingdom

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MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis

Interventions

LY2940680

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Lisa Lancaster, M.D.

  Endeavor Biomedicines

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2024
• First Posted: May 21, 2024
• Study Start: November 15, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (7); GB (9); MY (3); ME (8); FR (10); CA (6); AU (6); DE (6); BE (3); IE (4); IT (6); NZ (3); AR (5)