Givinostat in DMD: Results of the EPIDYS Study with Particular Attention to NSAA
Bibliographic record
Abstract
Background: Givinostat is a novel orally active histone deacetylase (HDAC) inhibitor being developed for the treatment of DMD. Methods: EPIDYS study is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study to evaluate the efficacy and safety of Givinostat in ambulant patients with DMD. A total of 179 boys aged ≥6 years at baseline affected by DMD were enrolled and 95% of them completed the study. Primary efficacy assessment was the time to climb 4 standard stairs (4SC). Six key secondary efficacy endpoints were included: physical function assessed by North Star Ambulatory Assessment (NSAA), time to rise from floor, distance walked in 6 minutes using 6-minute walk test, knee extension and elbow flexion quantitative muscle strength, and fat fraction of vastus lateralis muscle (VL MFF) evaluated by MR spectroscopy. Treatment duration was 18 months. Results: EPIDYS study met its primary endpoint and Givinostat demonstrated a statistically significant difference in change from baseline at 18 months in 4SC (GLS mean ratio [SD] = 0.86 [0.071]; p = 0.0345). Overall, treatment effect estimates relating to the key secondary endpoints consistently favored Givinostat over placebo supporting the primary endpoint result. NSAA was evaluated both as change from baseline at 18 months of the total score and as the cumulative loss of NSAA items. Givinostat treatment was associated with less decline in NSAA total score (mean difference: 1.91 points; nominal p = 0.021) as well as 39% less cumulative item loss (nominal p = 0.02). Givinostat treatment showed a good tolerability profile with primary issues being reversible and related to thrombocytopenia, and hypertriglyceridemia. Conclusion: EPIDYS study met its primary endpoint with consistent results in the key secondary endpoints. The treatment effects on physical function are considered clinically important and are related to how boys with DMD function in clinically meaningful motor tasks. Givinostat tolerability profile in study 48 was in line with results in previous studies in DMD and in other diseases. Publication History Article published online: 13 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".