Clinical trial NCT06422884: A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Progressive Fibrosing Interstitial Lung Disease
Keywords: taladegib
hedgehog pathway inhibitor
pulmonary fibrosis
Lead sponsor: Endeavor Biomedicines, Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-21
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Rate of change in percent predicted forced vital capacity (ppFVC) compared to placebo
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Absolute change in FVC (mL) compared to placebo
timeFrame: Baseline and Week 24
measure: Time to disease progression (absolute decline in ppFVC >10%, IPF-related hospitalization, or death) compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in the Living with Pulmonary Fibrosis Symptoms (L-PF Symptoms) Questionnaire Cough domain score compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in the L-PF Symptoms Questionnaire Dyspnea domain score compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in the L-PF Symptoms Questionnaire Fatigue domain score compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in total lung capacity (TLC) by chest high-resolution computed tomography (HRCT) imaging compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in % quantitative interstitial lung disease (QILD) by chest HRCT imaging compared to placebo compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in % quantitative ground glass opacity (QGG) by chest HRCT imaging compared to placebo
timeFrame: Baseline and Week 24
measure: Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Quilmes
country: Argentina
facility: Research Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Research Site
city: Buenos Aires
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Mendoza
country: Argentina
facility: Research Site
city: Camperdown
country: Australia
facility: Research Site
state: New South Wales
city: Macquarie Park
country: Australia
facility: Research Site
state: New South Wales
city: Brisbane
country: Australia
facility: Research Site
state: Queensland
city: South Brisbane
country: Australia
facility: Research Site
state: Queensland
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Melbourne
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Graz
country: Austria
facility: Research Site
state: Steiermark
city: Vienna
country: Austria
facility: Research Site
city: Dinant
country: Belgium
facility: Research Site
state: Namur
city: Brussels
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Ajax
country: Canada
facility: Research Site
state: Ontario
city: Montréal
country: Canada
facility: Research Site
state: Quebec
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Trois-Rivières
country: Canada
facility: Research Site
state: Quebec
city: Angers
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nantes
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Tours
country: France
facility: Research Site
city: Giessen
country: Germany
facility: Research Site
state: Hessen
city: Immenhausen
country: Germany
facility: Research Site
state: Hessen
city: Hannover
country: Germany
facility: Research Site
state: Lower Saxony
city: Essen
country: Germany
facility: Research Site
state: North Rhine-Westphalia
city: Berlin
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
state: Leinster
city: Dublin
country: Ireland
facility: Research Site
state: Leinster
city: Cork
country: Ireland
facility: Research Site
state: Munster
city: Dublin
country: Ireland
facility: Research Site
city: Bologna
country: Italy
facility: Research Site
state: Forli-Cesena
city: Padova
country: Italy
facility: Research Site
state: Padua
city: Florence
country: Italy
facility: Research Site
state: Tuscany
city: Catania
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Turin
country: Italy
facility: Research Site
city: Seoul
country: Korea, Republic of
facility: Research Site
state: (Deogyang District)
city: Ulsan
country: Korea, Republic of
facility: Research Site
state: (Dong District)
city: Seoul
country: Korea, Republic of
facility: Research Site
state: (Gangnam District)
city: Busan
country: Korea, Republic of
facility: Research Site
state: (Haeundae District)
city: Seoul
country: Korea, Republic of
facility: Research Site
state: (Seongbuk District)
city: Seoul
country: Korea, Republic of
facility: Research Site
state: (Songpa District)
city: Seoul
country: Korea, Republic of
facility: Research Site
state: (Yongsan District)
city: Seoul
country: Korea, Republic of
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Selangor
city: Kuala Lumpur
country: Malaysia
facility: Research Site
state: Selangor
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo Leon
city: San Nicolás De Los Garza
country: Mexico
facility: Research Site
state: Nuevo Leon
city: San Juan Del Río
country: Mexico
facility: Research Site
state: Queretaro
city: Chihuahua
country: Mexico
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
city: Oaxaca
country: Mexico
facility: Research Site
city: Puebla
country: Mexico
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Hamilton
country: New Zealand
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Birmingham
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Edinburgh
country: United Kingdom
facility: Research Site
city: Exeter
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Londonderry
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Endeavor Biomedicines
name: Lisa Lancaster, M.D.
role: STUDY_DIRECTOR
References: