J008 The phase 3 proof-hd trial demonstrates benefits of pridopidine on progression in Huntington Disease
Bibliographic record
Abstract
Introduction Pridopidine is a potent S1R agonist in clinical development for Huntington disease (HD). Aims To evaluate the safety and efficacy of pridopidine (45mg bid) in participants with early HD (TFC≥7). Methods Primary and key secondary endpoints were change to week 65 in total functional capacity (TFC) and cUHDRS, respectively. Additional endpoints included cognition (SWR), motor (Q-Motor) and Quality-of-Life (HD-QoL). Prespecified subgroup analyses excluded participants on antidopaminergic medications (ADMs) as ADMs are associated with faster functional and cognitive decline in HD. Results Pridopidine was well tolerated with a safety profile comparable to placebo. The primary and key secondary endpoints were not met in the full analysis set. In participants off ADMs, pridopidine shows improvement from baseline in cUHDRS up to week 52, with benefits at all timepoints through week 78. Pridopidine demonstrates maintenance or improvement from baseline in SWR and Q-Motor through week 78. Early improvements in Q-Motor are highly predictive of later benefits in function and cUHDRS. Pridopidine preserves quality-of-life through week 78. Subjects on lower doses of ADMs maintain the positive effects of pridopidine. Subjects on higher doses of ADMs show blunting of pridopidine’s benefit for numerous endpoints, and plasma levels of VMAT2 inhibitors are elevated in the presence of pridopidine (CYP2D6 inhibitor). Conclusions Pridopidine shows consistent, sustained, and clinically meaningful benefits across multiple endpoints including function, disease progression, cognition, motor and QoL in subjects off and on low doses of ADMs. Remarkably, pridopidine demonstrated unprecedented improvements from baseline in cUHDRS, SWR, Q-Motor and HD-QoL, for at least 1 year.
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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 | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.014 | 0.002 |
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".