A Phase 2, Randomized, Placebo-Controlled Trial to Evaluate the Effects of SAGE-718 in Patients with Alzheimer’s Disease: Study Design (P8-6.010)
Notice bibliographique
Résumé
Objective: To describe the design of a Phase 2, randomized, double-blind, placebo-controlled study evaluating the effect of SAGE-718 on cognitive performance in patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer’s disease (AD). Background: Executive functioning and learning and memory deficits associated with AD occur early in the disease. There is an unmet need for effective treatments that address early cognitive impairment in patients with AD. SAGE-718, an investigational N-methyl-D-aspartate receptor positive allosteric modulator, is being evaluated for the treatment of cognitive impairment due to AD and other neurodegenerative disorders. Design/Methods: Approximately 150 patients will be enrolled across 40 US sites. Eligible patients aged 50–80 years meeting diagnostic criteria for MCI or mild dementia due to AD with a baseline Montreal Cognitive Assessment score of 15–25, a baseline Clinical Dementia Rating score of 0.5–1.0 (inclusive), and a memory box score ≥0.5 will be randomized to receive oral SAGE-718 or placebo for 3 months. The study includes: a 3-week screening period, 1-week baseline period, 12-week treatment period, and a 4-week follow-up period. During the 12-week treatment period, patients will either receive SAGE-718 (initial dose for 6 weeks followed by a lower dose for the next 6 weeks) or matching placebo. The primary endpoint is change from baseline to Day 84 in the Coding Test (total correct) from the Wechsler Adult Intelligence Scale Fourth Edition (WAIS-IV). Secondary endpoints are safety and tolerability, including the number of study withdrawals due to treatment-emergent adverse events and study discontinuations. Other exploratory cognitive and functional endpoints will be evaluated. Results: Study initiation is planned for late 2022. Conclusions: This randomized, placebo-controlled study is intended to evaluate the effects of SAGE-718 on cognitive performance and assess safety and tolerability in patients with MCI or mild dementia due to AD. Results will further inform the emerging clinical profile of SAGE-718. Disclosure: Dr. Lago has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Lago has stock in Sage Therapeutics. Aaron Koenig has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Johannesen has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Johannesen has stock in Sage Therapeutics . Dr. Johannesen has received research support from National Institute of Health. Dr. Johannesen has received research support from Brain & Behavior Research Foundation . Dr. Johannesen has received research support from VA office of Rehabilitation Research & Development. Dr. Park has nothing to disclose. Sigui Li has received personal compensation for serving as an employee of SAGE Therapeutics. Ms. Freitag has nothing to disclose. Jeffrey Wald has received personal compensation for serving as an employee of Sage Therapeutics. Jeffrey Wald has received stock or an ownership interest from Sage Thereapeutics. Dr. Paumier has nothing to disclose. Michael Quirk has received personal compensation for serving as an employee of Sage Therapeutics. Michael Quirk has received stock or an ownership interest from Sage Therapeutics. Dr. Doherty has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Doherty has received stock or an ownership interest from Sage Therapeutics.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,003 | 0,002 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,003 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,012 | 0,002 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».