RCT Abstract - ENV-101 for the treatment of idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled phase 2 trial
Bibliographic record
Abstract
Background: The hedgehog (Hh) signaling pathway promotes fibrosis in idiopathic pulmonary fibrosis (IPF), an interstitial lung disease with a high mortality rate. Currently, there is no cure for IPF, and available antifibrotics only slow the rate of decline in lung function in IPF. We aimed to assess the safety and efficacy of ENV-101 (taladegib) in IPF, an Hh pathway inhibitor, in a phase 2a, proof-of-concept clinical trial. Methods: ENV-IPF-101 ( NCT04968574 ) was a phase 2a, randomised, double-blind placebo-controlled trial conducted at 16 clinical sites in Australia, Canada, Malaysia, Mexico, and South Korea for patients with IPF older than 40 years of age who were not treated with concurrent IPF therapy. Patients were randomised to ENV-101 200 mg or placebo equivalent once daily orally for 12 weeks with a 6-week follow-up. The main outcomes were safety in the intention-to-treat population and change from baseline in forced vital capacity (FVC) in the efficacy-evaluable population. Exploratory outcomes were measures of fibrosis on high-resolution computed tomography (HRCT) in the efficacy-evaluable population. Findings: Between August 12, 2021, and July 28, 2023, 41 patients were randomised. Twenty-one patients were randomly allocated to the ENV-101 treatment arm (3 [14%], female; 18 [86%], male) and 20 to the placebo arm (4 [20%], female; 16 [80%], male). All treatment-emergent adverse events (TEAEs) possibly or probably related to the study drug were grade 1 or 2, all except one were mild or moderate in severity, and none were serious AEs. The most common TEAEs in the ENV-101 arms were dysgeusia (12/21 [57%]), muscle spasms (12/21 [57%), and alopecia (11/21 [52%]). No deaths occurred during this study. Patients treated with ENV-101 experienced an improvement from baseline in FVC and across multiple HRCT-based measures of disease. Between-arm differences in change from baseline to week 12 favored ENV-101 for the efficacy measures % predicted FVC (3·95%; 95% confidence interval [CI], 0·31% to 7·60%; p=0·035), total lung capacity by HRCT (257·0 mL; 95% CI, 86·8 to 427·2 mL; p=0·004), and % quantitative interstitial lung disease (–7·5%; p=0·047; 95% CI, –18·3 to –0·56). Interpretation: The acceptable safety profile and efficacy analyses of ENV-101 support further investigation in a phase 2b trial in patients with IPF (WHISTLE-PF).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.004 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.004 | 0.003 |
| Insufficient payload (model declined to judge) | 0.037 | 0.004 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".