Idiopathic Pulmonary FibrosisPhase 2NCT06422884
A Phase 2 Trial of ENV-101 in Patients With Lung Fibrosis (WHISTLE-PF Trial)
A Phase 2 study testing ENV-101 in people with Idiopathic Pulmonary Fibrosis and Progressive Fibrosing Interstitial Lung Disease, run by Endeavor Biomedicines, Inc. at 78 sites in 14 countries.
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). Another goal of this study is to better understand the safety and tolerability of ENV-101 in this patient population. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis, Progressive Fibrosing Interstitial Lung Disease
- What is being tested?
- ENV-101
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 213 participants
- Where
- 78 sitesin 14 countries
- Study dates
- 15 Nov 2024to Oct 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 27Show fewer
- 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
- Riociguat
- Prostacyclin or prostacyclin analogue
- Radiation to the lungs
- 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.
Trial locations and contacts
78 sites in 14 countries.
78 sites in 14 countries
France10 sites
Research Site
Angers, 49933
Research Site
Bordeaux, 33604
Research Site
Caen, 14033
Research Site
Dijon, 21000
Research Site
Montpellier, 34090
Research Site
Nantes, 44093
Research Site
Paris, 75014
Research Site
Paris, 94270
Research Site
Rennes, 35033
Research Site
Tours, 37044
United Kingdom9 sites
Research Site
Belfast, BT9 7AB
Research Site
Birmingham, B15 2GW
Research Site
Birmingham, B9 5SS
Research Site
Cambridge, CB2 0AY
Research Site
Edinburgh, EH1 3EG
Research Site
Exeter, EX2 5DW
Research Site
Leicester, LE3 9QP
Research Site
London, SW3 6NP
Research Site
Londonderry, BT47 6SB
Mexico8 sites
Research Site
Chihuahua City, 31230
Research Site
Mexico City, 14080
Research Site
Monterrey, Nuevo León, 64060
Research Site
Monterrey, Nuevo León, 64718
Research Site
Oaxaca City, 68000
Research Site
Puebla City, 72180
Research Site
San Juan del Río, Querétaro, 76800
Research Site
San Nicolás de los Garza, Nuevo León, 66465
South Korea7 sites
Research Site
Busan, (Haeundae District), 48108
Research Site
Seoul, (Deogyang District), 10475
Research Site
Seoul, (Seongbuk District), 02841
Research Site
Seoul, (Songpa District), 05505
Research Site
Seoul, (Yongsan District), 04401
Research Site
Seoul, 16499
Research Site
Ulsan, (Dong District), 44033
Australia6 sites
Research Site
Box Hill, Victoria, 3128
Research Site
Brisbane, Queensland, 4032
Research Site
Camperdown, New South Wales, 2050
Research Site
Macquarie Park, New South Wales, 2109
Research Site
Nedlands, Western Australia, 6009
Research Site
South Brisbane, Queensland, 4101
Canada6 sites
Research Site
Ajax, Ontario, L1S 2J5
Research Site
Edmonton, Alberta, T6G 2C8
Research Site
Montreal, Quebec, H2X 0A9
Research Site
Sherbrooke, Quebec, J1H 5N4
Research Site
Trois-Rivières, Quebec, G8T 7A1
Research Site
Vancouver, British Columbia, V6Z 2K5
Germany6 sites
Research Site
Berlin, 13125
Research Site
Essen, North Rhine-Westphalia, 45239
Research Site
Giessen, Hesse, 35398
Research Site
Hanover, Lower Saxony, 30625
Research Site
Immenhausen, Hesse, 34376
Research Site
Leipzig, 4103
Italy6 sites
Research Site
Bologna, Forli-Cesena, 47121
Research Site
Catania, 95123
Research Site
Florence, Tuscany, 50314
Research Site
Milan, 20123
Research Site
Padova, Padua, 35128
Research Site
Turin, 10126
Argentina5 sites
Research Site
Buenos Aires, 1888
Research Site
Buenos Aires, C1426ABP
Research Site
Mendoza, 5501
Research Site
Mendoza, CP 5500
Research Site
Quilmes, Buenos Aires, B1878FNR
Ireland4 sites
Research Site
Cork, Munster, T12 DC4A
Research Site
Dublin, Leinster, D05 AT88
Research Site
Dublin, Leinster, D07 A8NN
Research Site
Dublin, D04 T6F4
Belgium3 sites
Research Site
Brussels, 1070
Research Site
Brussels, 1200
Research Site
Dinant, Namur, 5500
Malaysia3 sites
Research Site
Kuala Lumpur, Selangor, 42300
Research Site
Kuala Lumpur, Selangor, 50590
Research Site
Kuala Lumpur, Selangor, 56000
New Zealand3 sites
Research Site
Auckland
Research Site
Christchurch, 8011
Research Site
Hamilton
About this study
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)
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.
Read the 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.
- Being tested
- ENV-101, Placebo
- Keywords
- taladegib, hedgehog pathway inhibitor, pulmonary fibrosis
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ENV-101Drug
Also called taladegib
oral tablet, dosed once a day
PlaceboDrug
oral tablet, dosed once a day
| Study group | Role | What they receive |
|---|---|---|
| ENV-101 Low Dose (IPF Population) | Experimental | Not described Receives: Drug: ENV-101 |
| ENV-101 Mid Dose (IPF Population) | Experimental | Not described Receives: Drug: ENV-101 |
| ENV-101 High Dose (IPF Population) | Experimental | Not described Receives: Drug: ENV-101 |
| Placebo (IPF Population) | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in percent predicted forced vital capacity (ppFVC) compared to placebo
ppFVC is a measure of lung function
Measured: Baseline and Week 24
Secondary outcomes (11)
Absolute change in FVC (mL) compared to placebo
FVC is a measure of lung function
Measured: Baseline and Week 24
Time to disease progression (absolute decline in ppFVC >10%, IPF-related hospitalization, or death) compared to placebo
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline and Week 24
Absolute change in % quantitative interstitial lung disease (QILD) by chest HRCT imaging compared to placebo compared to placebo
Measured: Baseline and Week 24
Absolute change in % quantitative ground glass opacity (QGG) by chest HRCT imaging compared to placebo
Measured: Baseline and Week 24
Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo
Measured: Baseline and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start15 Nov 2024
- Primary completionOct 2026 (estimated)
- Study completionOct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 213 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endeavor Biomedicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lisa Lancaster, M.D., Study director, Endeavor Biomedicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06422884
- Sponsor's protocol ID
- ENV-IPF-103
- Status last verified
- Feb 2026
- First submitted
- 15 May 2024
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06422884
- Acronym / sponsor ID
- ENV-IPF-103
- Keywords
- taladegib, hedgehog pathway inhibitor, pulmonary fibrosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 213 participants (actual)
- Lead sponsor
- Endeavor Biomedicines, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Nov 2024 (actual)
- Primary completion
- Oct 2026 (estimated)
- Study completion
- Oct 2026 (estimated)
- First posted
- 21 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (27 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ENV-101Also: taladegiboral tablet, dosed once a day | Drug | ENV-101 High Dose (IPF Population), ENV-101 Low Dose (IPF Population), ENV-101 Mid Dose (IPF Population) |
| Placebooral tablet, dosed once a day | Drug | Placebo (IPF Population) |
Primary outcome
Change in percent predicted forced vital capacity (ppFVC) compared to placebo
Time frame: Baseline and Week 24
ppFVC is a measure of lung function
11 secondary outcomes
Absolute change in FVC (mL) compared to placebo
Time frame: 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
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
Absolute change in the L-PF Symptoms Questionnaire Dyspnea domain score compared to placebo
Time frame: Baseline and Week 24
Absolute change in the L-PF Symptoms Questionnaire Fatigue domain score compared to placebo
Time frame: Baseline and Week 24
Absolute change in the L-PF Symptoms module score compared to placebo
Time frame: Baseline and Week 24
Absolute change in the L-PF Impacts module score compared to placebo
Time frame: 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
Absolute change in % quantitative interstitial lung disease (QILD) by chest HRCT imaging compared to placebo compared to placebo
Time frame: 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
Absolute change in % quantitative lung fibrosis (QLF) by chest HRCT imaging compared to placebo
Time frame: Baseline and Week 24
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lisa Lancaster, M.D. study director
Endeavor Biomedicines
78 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ENV-101 in people with Idiopathic Pulmonary Fibrosis and Progressive Fibrosing Interstitial Lung Disease, run by Endeavor Biomedicines, Inc. at 78 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 78 sites in France, United Kingdom, Mexico, South Korea, Australia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in percent predicted forced vital capacity (ppFVC) compared to placebo (time frame: Baseline and Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.