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

May 15, 2024 updated by: Endeavor Biomedicines, Inc.

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) and progressive pulmonary fibrosis (PPF). Another goal of this study is to better understand the safety and tolerability of ENV-101 in these patient populations.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This trial is a 6-month, randomized, double-blind, controlled, dose-ranging trial of ENV-101 in two parallel cohorts of adult patients with lung fibrosis: idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF). 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 in each indication.

Study Type

Interventional

Enrollment (Estimated)

320

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • IPF Population: Patients ≥ 40 years old with an IPF diagnosis as confirmed by the Investigator.
  • PPF Population: Patients ≥ 18 years old (or the minimum legal adult age, whichever is greater) with a diagnosis of PPF, 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:

  • IPF Population: 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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
Experimental: ENV-101 Low Dose (PPF Population)
Drug: ENV-101
oral tablet, dosed once a day
Other Names:
  • taladegib
Experimental: ENV-101 Mid Dose (PPF Population)
Drug: ENV-101
oral tablet, dosed once a day
Other Names:
  • taladegib
Experimental: ENV-101 High Dose (PPF Population)
Drug: ENV-101
oral tablet, dosed once a day
Other Names:
  • taladegib
Placebo Comparator: Placebo (PPF Population)
Drug: Placebo
oral tablet, dosed once a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
IPF Population Primary Endpoint: Rate of change in percent predicted forced vital capacity (ppFVC) compared to placebo
Time Frame: Baseline and Week 24
ppFVC is a measure of lung function
Baseline and Week 24
PPF Population Primary Endpoint: Safety
Time Frame: Baseline and Week 24
The incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), and treatment-emergent and clinically significant changes in lab parameters, vital signs, electrocardiogram (ECG), and oxygen saturation
Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PPF Population: Rate of change in ppFVC compared to placebo
Time Frame: Baseline and Week 24
Baseline and Week 24
Absolute change in FVC (mL) compared to placebo
Time Frame: Baseline and Week 24
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
Time Frame: Baseline and Week 24
Baseline and Week 24
Absolute change in the Living with Pulmonary Fibrosis Symptoms (L-PF Symptoms) Questionnaire Cough domain score compared to placebo
Time Frame: Baseline and Week 24
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
Time Frame: Baseline and Week 24
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
Time Frame: Baseline and Week 24
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
Time Frame: Baseline and Week 24
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
Time Frame: Baseline and Week 24
Baseline and Week 24
Absolute change in % quantitative ground glass opacity (QGG) by chest HRCT imaging compared to placebo
Time Frame: Baseline and Week 24
Baseline and Week 24
Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo
Time Frame: Baseline and Week 24
Baseline and Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Endeavor Biomedicines, Inc.

Investigators

  • Study Director: Paul Frohna, M.D., Ph.D., Pharm.D., Endeavor Biomedicines

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

September 1, 2024

Primary Completion (Estimated)

June 1, 2026

Study Completion (Estimated)

June 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)

May 21, 2024

Last Update Submitted That Met QC Criteria

May 15, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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