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

Idiopathic Pulmonary Fibrosis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06422884
• Other study ID #: ENV-IPF-103
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 2024
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: Endeavor Biomedicines, Inc.
• Contact: Endeavor Clinical Trials
• Phone: 1-858-727-3199
• Email: ebmclinical[@]endeavorbiomedicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 320
• Est. completion date: June 2026
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis

Intervention

Drug:
• ENV-101
oral tablet, dosed once a day
• Placebo
oral tablet, dosed once a day

Locations

Country	Name	City	State
Australia	Research Site	Adelaide	South Australia
Australia	Research Site	Box Hill	Victoria
Australia	Research Site	Melbourne	Victoria
Australia	Research Site	Nedlands	Western Australia
Australia	Research Site	South Brisbane	Queensland
Austria	Research Site	Vienna
Canada	Research Site	Sherbrooke	Quebec
Canada	Research Site	Vancouver	British Columbia
Germany	Research Site	Munich
Ireland	Research Site	Dublin
Korea, Republic of	Research Site	Busan	(Haeundae District)
Korea, Republic of	Research Site	Seoul	(Seongbuk District)
Korea, Republic of	Research Site	Seoul	(Songpa District)
Korea, Republic of	Research Site	Seoul	(Yongsan District)
Korea, Republic of	Research Site	Seoul	(Gangnam District)
Korea, Republic of	Research Site	Ulsan	(Dong District)
Malaysia	Research Site	Kuala Lumpur
Malaysia	Research Site	Selayang Baru Utara
Mexico	Research Site	Chihuahua
Mexico	Research Site	Mexico City
Mexico	Research Site	Monterrey	Nuevo Leon
Mexico	Research Site	Monterrey	Nuevo Leon
Mexico	Research Site	Oaxaca
Mexico	Research Site	Puebla
Mexico	Research Site	San Juan Del Río	Queretaro
Mexico	Research Site	San Nicolás De Los Garza	Nuevo Leon
Switzerland	Research Site	Bern
United Kingdom	Research Site	Edinburgh
United Kingdom	Research Site	Exeter
United Kingdom	Research Site	London
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Birmingham	Alabama
United States	Research Site	Dallas	Texas
United States	Research Site	Gainesville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Maywood	Illinois
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Portland	Oregon
United States	Research Site	Royal Oak	Michigan
United States	Research Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Endeavor Biomedicines, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Germany,  Ireland,  Korea, Republic of,  Malaysia,  Mexico,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IPF Population Primary Endpoint: Rate of change in percent predicted forced vital capacity (ppFVC) compared to placebo	ppFVC is a measure of lung function	Baseline and Week 24
Primary	PPF Population Primary Endpoint: Safety	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	PPF Population: Rate of change in ppFVC compared to placebo		Baseline and Week 24
Secondary	Absolute change in FVC (mL) compared to placebo	FVC is a measure of lung function	Baseline and Week 24
Secondary	Time to disease progression (absolute decline in ppFVC >10%, IPF-related hospitalization, or death) compared to placebo		Baseline and Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Absolute change in % quantitative interstitial lung disease (QILD) by chest HRCT imaging compared to placebo compared to placebo		Baseline and Week 24
Secondary	Absolute change in % quantitative ground glass opacity (QGG) by chest HRCT imaging compared to placebo		Baseline and Week 24
Secondary	Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo		Baseline and Week 24