ENV-101 for Pulmonary Fibrosis

Recruiting at66 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this 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.

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.

How is the drug ENV-101 different from other treatments for pulmonary fibrosis?

ENV-101 (taladegib) is unique because it targets the Hedgehog signaling pathway, which is involved in tissue repair and fibrosis, offering a novel approach compared to existing treatments like pirfenidone that focus on reducing inflammation and fibrosis through different mechanisms. ^{1 2 3 4 5}

Research Team

John Huetsch, M.D.

Principal Investigator

Endeavor Biomedicines

Eligibility Criteria

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

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

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 been hospitalized for a serious illness in the last 3 months.

Trial Timeline

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

Treatment Details

Interventions

• ENV-101 (Anti-fibrotic Agent)

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Pirfenidone in patients with unclassifiable progressive fibrosing interstitial lung disease: a double-blind, randomised, placebo-controlled, phase 2 trial. [2021]

3. England 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. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Antifibrotic activities of pirfenidone in animal models. [2022]