Clinical trial NCT04968574: A Study Evaluating the Safety and Efficacy of ENV-101 in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase 2, Multi-Center Study Evaluating the Safety and Efficacy of ENV-101 (Taladegib) in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: hedgehog
smoothened
pulmonary fibrosis
Lead sponsor: Endeavor Biomedicines, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-20
Enrollment: 41
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: This is a Phase 2, randomized, placebo controlled, multi-center study in subjects with mild to moderate IPF. Eligible subjects will be randomized to receive placebo or ENV-101 as a daily oral dose for 12 consecutive weeks of treatment. Following treatment, subjects will be observed for an additional 6 weeks.


Eligibility criteria: Inclusion Criteria:

* IPF diagnosis based upon American Thoracic Association, Japanese Respiratory Society, European Respiratory Society, Latin American Thoracic Association guidelines within the last 7 years. Diagnosis will be confirmed to be consistent with IPF by centrally read high resolution computed tomography (HRCT).
* Ability to successfully perform lung function tests.
* Subjects are willing to remain on study treatment for the duration of the study.
* Subjects have a full understanding of the informed consent.

Exclusion Criteria:

* Evidence of other known causes of interstitial lung disease (ILD) (e.g., domestic, and occupational environmental exposures, connective tissue disease \[CTD\], and drug toxicity), lung transplant expected within 12 months of screening or evidence of clinically significant lung disease other than IPF including but not limited to asthma, chronic obstructive pulmonary disease (COPD), uncontrolled pulmonary hypertension and emphysema where computed tomography (CT)-assessed extent of emphysema is greater than extent of fibrosis.
* History of malignancy, including carcinoma during the preceding 5 years. With the following exceptions:

  1. Prior history of in situ basal or squamous cell skin cancer that was successfully treated with curative therapies.
  2. Subjects with other malignancies if they have been continuously disease free for at least 5 years prior to study start.
  3. Subjects with prostate cancer that are managed by surveillance are also eligible.
* Current use of supplemental oxygen for any condition unless prior approval is received from the Sponsor.
* Smoking within 6 months of study start, current smoker, or unwillingness to refrain from smoking during the clinical trial duration.
* Presence of active infection at study start or confirmed active human immunodeficiency virus (HIV), Hepatitis B virus (HBV) or Hepatitis C virus (HCV).
* Occurrence of serious illness requiring hospitalization within 90 days prior to study start.
* Current or previous use (within 30 days prior to study start) of the following:

  1. N-acetylcysteine
  2. endothelin receptor antagonist
  3. riociguat
  4. prostacyclin or prostacyclin analogue
  5. Warfarin for IPF
  6. Cytotoxic agents (e.g., colchicine if used for IPF)
  7. Radiation to the lungs
  8. Pulmonary rehabilitation
  9. Investigational agent for IPF
  10. Immunosuppressive medications (e.g., methotrexate, azathioprine)
  11. Systemic or inhaled glucocorticosteroids
  12. Antifibrotic therapy (e.g., nintedanib, pirfenidone)
* Regular use of phosphodiesterase type-5 inhibitor, occasional use for erectile dysfunction will be allowed.
* Use of drugs that are known moderate or stronger CYP3A4 inhibitors or inducers within 12 days prior to study start.
* Males and females 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.
* Females that are pregnant or nursing.
* Females and males that are unwilling to refrain from blood or blood product donation for the duration of the study and for 30 days after their final study dose.
* 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 study dose.
* Subjects with a history of a severe allergic reaction or anaphylactic reaction or known hypersensitivity to any component of ENV-101.
* Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study investigative site or the study Sponsor.

Primary outcomes:
measure: Change from baseline in frequency of adverse events (AEs)
timeFrame: Baseline to Week 18
measure: Change from baseline in severity of AEs
timeFrame: Baseline to Week 18
measure: Change from baseline in vital sign measurements - pulse
timeFrame: Baseline to Week 18
measure: Change from baseline in vital sign measurements - blood pressure
timeFrame: Baseline to Week 18
measure: Change from baseline in vital sign measurements - respiration rate
timeFrame: Baseline to Week 18
measure: Change from baseline in vital sign measurements - temperature
timeFrame: Baseline to Week 18
measure: Change from baseline in blood oxygen saturation level
timeFrame: Baseline to Week 18
measure: Incidence of clinical laboratory abnormalities
timeFrame: Baseline to Week 18
measure: Severity of clinical laboratory abnormalities
timeFrame: Baseline to Week 18
measure: Number of hospitalizations
timeFrame: Baseline to Week 18
Secondary outcomes:
measure: Change from baseline of FVC (forced vital capacity)
timeFrame: Baseline and Week 12
measure: Change from baseline of DLCO (diffusing capacity of the lungs for carbon monoxide)
timeFrame: Baseline and Week 12
measure: Change from baseline of patient reported outcomes by the University of California-San Diego (UCSD) Shortness of Breath Questionnaire (SOBQ)
timeFrame: Baseline and Week 12
Other outcomes:
measure: Change from baseline of FVC
timeFrame: Baseline and Week 6
measure: Change from baseline of FVC
timeFrame: Baseline and Week 18
measure: Change from baseline of DLCO
timeFrame: Baseline and Week 6
measure: Change from baseline of DLCO
timeFrame: Baseline and Week 18
measure: Change from baseline of patient reported outcomes by the UCSD SOBQ
timeFrame: Baseline and Week 6
measure: Change from baseline of patient reported outcomes by the UCSD SOBQ
timeFrame: Baseline and Week 18
Locations:
city: Liverpool
country: Australia
facility: Research Site
state: New South Wales
city: Benowa
country: Australia
facility: Research Site
state: Queensland
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Sherbrooke
country: Canada
facility: Research Site
state: Quebec
city: Incheon
country: Korea, Republic of
facility: Research Site (Namdong District)
city: Seongnam
country: Korea, Republic of
facility: Research Site (Bundang District)
city: Seoul
country: Korea, Republic of
facility: Research Site (Gangnam District)
city: Seoul
country: Korea, Republic of
facility: Research Site (Seongbuk District)
city: Seoul
country: Korea, Republic of
facility: Research Site (Songpa District)
city: Batu Caves
country: Malaysia
facility: Research Site
city: Kota Bharu
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Site
city: Kuala Lumpur
country: Malaysia
facility: Research Sire
city: Kuala Lumpur
country: Malaysia
facility: Research Site
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: Chihuahua
country: Mexico
facility: Research Site
city: Mexico City
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
Study officials:
affiliation: Endeavor Biomedicines
name: John Huetsch, M.D.
role: STUDY_DIRECTOR
References: