ENV-101 for Pulmonary Fibrosis

Recruiting at 88 trial locations

Overseen By Endeavor Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Endeavor Biomedicines, Inc.

Must be taking: Antifibrotics, Immunosuppressants

Must not be taking: Endothelin antagonists, Riociguat

Disqualifiers: Smoking, Malignancy, Hepatic impairment, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ENV-101 (also known as taladegib) for idiopathic pulmonary fibrosis (IPF), a lung disease that causes scarring and affects breathing. The main goal is to assess how ENV-101 impacts lung function and the scarring process, while also evaluating the treatment's safety and tolerability for patients. Participants will receive different doses of ENV-101 or a placebo to compare results. The trial seeks individuals diagnosed with IPF who have stable lung function and are not currently smoking or using certain medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in IPF treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, you need to have been on stable treatment with standard care for at least 3 months or not treated for at least 8 weeks before starting the study. Some specific medications must be stopped before the trial, such as certain drugs affecting liver enzymes and some immunosuppressants.

Is there any evidence suggesting that ENV-101 is likely to be safe for humans?

Research has shown that ENV-101, also known as taladegib, has been tested in people with idiopathic pulmonary fibrosis (IPF). In these studies, participants generally found ENV-101 safe and well-tolerated. Some side effects occurred, but none were serious enough to halt the research.

The studies tested different doses, similar to those in the current trial. The results support further investigation of ENV-101 to better understand its safety and potential benefits for lung function in people with IPF.

For those considering joining a trial, this information indicates that ENV-101 has been safe enough in past studies to warrant continued testing. However, discussing any concerns with a doctor is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about ENV-101 for pulmonary fibrosis because it targets the disease differently from current treatments like pirfenidone and nintedanib. Unlike these standard medications that primarily slow disease progression, ENV-101 is designed to actively repair and regenerate lung tissue, potentially reversing damage rather than just managing symptoms. Additionally, ENV-101 offers dosing flexibility with its high, mid, and low-dose options, allowing for personalized treatment approaches that could better meet individual patient needs.

What evidence suggests that ENV-101 might be an effective treatment for idiopathic pulmonary fibrosis?

Research has shown that ENV-101, also known as taladegib, may help treat idiopathic pulmonary fibrosis (IPF). This trial will test different doses of ENV-101, including high, mid, and low doses, along with a placebo. Studies found that patients taking ENV-101 experienced better lung function and increased lung capacity. Important measures of lung health, such as forced vital capacity (FVC)—the amount of air exhaled—improved from the start of treatment. Most patients tolerated the treatment well, with side effects usually mild to moderate. These findings suggest that ENV-101 could effectively manage IPF. ^{1 2 3 6 7}

Who Is on the Research Team?

Lisa Lancaster, M.D.

Principal Investigator

Endeavor Biomedicines

Are You a Good Fit for This Trial?

Adults with idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF) are eligible for this trial. Specific criteria will determine who can join, but the main requirement is a diagnosis of lung fibrosis.

Inclusion Criteria

Percent predicted diffusing capacity of lung for carbon monoxide (DLCO) ≥ 25%, adjusted for hemoglobin (Hgb) at study start

I am 40 or older and have been diagnosed with IPF.

I can perform breathing tests.

Exclusion Criteria

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

I have not had any cancer, except for certain types, in the last 5 years.

I have not been hospitalized for a serious illness in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized doses of ENV-101 or placebo for 6 months

24 weeks

Regular visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ENV-101

Trial Overview The WHISTLE-PF Trial is testing ENV-101's effects on lung function and fibrosis in patients compared to a placebo. The study aims to understand how well ENV-101 works and its safety.

How Is the Trial Designed?

Group I: ENV-101 Mid Dose (IPF Population) Experimental Treatment 1 Intervention

Group II: ENV-101 Low Dose (IPF Population) Experimental Treatment 1 Intervention

Group III: ENV-101 High Dose (IPF Population) Experimental Treatment 1 Intervention

Group IV: Placebo (IPF Population) Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Endeavor Biomedicines, Inc.

Lead Sponsor

Trials

4

Recruited

310+

Published Research Related to This Trial

In a study involving 13 patients with idiopathic pulmonary fibrosis (IPF), pirfenidone treatment did not significantly reduce the number of fibroblast foci, indicating that its anti-fibrotic effects may not be immediately observable in tissue samples after 6 months.

Despite the lack of significant changes in fibroblast foci and proliferation markers, the treatment was well-tolerated, and there was an increase in certain cytokines associated with angiogenesis and anti-inflammation, suggesting potential immunomodulatory effects of pirfenidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. Ronan, N., Bennett, DM., Khan, KA., et al.[2019]

A new small-molecule inhibitor targeting the αvβ1 integrin was developed, which is crucial for understanding its role in diseases, particularly in activating TGFβ1, a key factor in fibrosis.

This inhibitor showed promising results in reducing pulmonary and liver fibrosis in animal models, indicating its potential as a therapeutic option for conditions involving excessive tissue scarring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. Reed, NI., Jo, H., Chen, C., et al.[2022]

The inhaled drug GSK3008348 demonstrated a 20% reduction in lung volume distribution in patients with idiopathic pulmonary fibrosis (IPF), indicating effective target engagement of the αvβ6 integrin in the lungs.

The study, involving 8 participants, showed that GSK3008348 was well tolerated with no serious adverse events, suggesting a favorable safety profile for this novel treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A positron emission tomography imaging study to confirm target engagement in the lungs of patients with idiopathic pulmonary fibrosis following a single dose of a novel inhaled αvβ6 integrin inhibitor. Maher, TM., Simpson, JK., Porter, JC., et al.[2020]

In a phase 2 trial involving 253 patients with progressive fibrosing unclassifiable interstitial lung disease (ILD), pirfenidone showed a significant reduction in the decline of lung function compared to placebo, suggesting it may be an effective treatment option.

The safety profile of pirfenidone was acceptable, with common side effects including gastrointestinal disorders and fatigue, but no significant differences in serious adverse events compared to placebo, indicating it is generally well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. Maher, TM., Corte, TJ., Fischer, A., et al.[2021]

Pirfenidone has shown consistent antifibrotic activity in various animal models, including those for lung, liver, heart, and kidney fibrosis, suggesting its potential effectiveness in treating fibrotic diseases.

The mechanism of action for pirfenidone involves the modulation of cytokines and growth factors, particularly reducing transforming growth factor-β, which is linked to the progression of fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antifibrotic activities of pirfenidone in animal models. Schaefer, CJ., Ruhrmund, DW., Pan, L., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41043447/?utm_source=FeedFetcher&utm_medium=rss&utm_campaign=None&utm_content=1T5FW5K6kI73iaYFcm6n6ILcuJDBKumLJYi5zjRCdcUGYRRQ1&fc=None&ff=20251101223229&v=2.18.0.post22+67771e2

Taladegib for the treatment of idiopathic pulmonary fibrosis ... The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy- ...

2. endeavorbiomedicines.com endeavorbiomedicines.com/endeavor-biomedicines-announces-publication-of-positive-data-from-phase-2a-trial-in-the-lancet-respiratory-medicine-evaluating-taladegib-env101-in-individuals-with-idiopathic-pulmonary-fibrosis/

Treatment with taladegib demonstrated improved lung ... Treatment with taladegib demonstrated improved lung function from baseline, increased total lung capacity and reversed key measures of lung ...

3. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(25)00239-5/abstract

Taladegib for the treatment of idiopathic pulmonary fibrosis ... The primary outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy- ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04968574

NCT04968574 | A Study Evaluating the Safety and Efficacy ... A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF). ClinicalTrials.gov ID NCT04968574. Sponsor ...

5. hcplive.com hcplive.com/view/taladegib-shows-potential-improve-fvc-idiopathic-pulmonary-fibrosis

Taladegib Shows Potential to Improve FVC in Idiopathic ... The therapy was well-tolerated in the phase 2a ENV-IPF-101 trial, with mostly mild-to-moderate TEAEs related to treatment.

6. endeavorbiomedicines.com endeavorbiomedicines.com/our-science/env-101/

ENV-101 | Changing the Trajectory of Fibrotic Lung Diseases Data from a Phase 2a, randomized, double-blind, placebo-controlled clinical trial that evaluated safety and efficacy of taladegib vs. placebo in 41 patients ...

7. atsjournals.org atsjournals.org/doi/abs/10.1164/ajrccm.2025.211.Abstracts.A2634

WHISTLE-PF: Study Design of a Phase 2b, Multi-center ... ENV-101 (taladegib) is a small molecule Hh inhibitor (Hhi), whose safety and efficacy in IPF were investigated in a recent 12-week Phase 2a, randomized, double- ...