Dataset Information

The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review.

ABSTRACT: Nearly 35 million people worldwide live with Alzheimer's disease (AD). The prevalence of the disease is expected to rise two-fold by 2050. With only symptomatic treatment options available, it is essential to understand the developments and existing evidence that aims to target brain pathology and dementia outcomes. This scoping systematic review aimed to collate existing evidence of CT1812 for use in patients with AD and summarize the methodologies of ongoing trials. Adhering to PRISMA Statement 2020 guidelines, PubMed/MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were systematically searched through up to 15 November 2022 by applying the following keywords: CT1812, Alzheimer's disease, dementia, and/or sigma-2 receptor. Three completed clinical trials were included along with three ongoing records of clinical trials. The three completed trials were in Phases I and II of testing. The sample size across all three trials was 135. CT1812 reached endpoints across the trials and obtained a maximum concentration in the cerebrospinal fluid with 97-98% receptor occupancy. The findings of this systematic review must be used with caution as the results, while mostly favorable so far, must be replicated in higher-powered, placebo-controlled Phase II-III trials.

SUBMITTER: Rasheed A

PROVIDER: S-EPMC9866790 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review.

Rasheed Anum A Zaheer Ahmad Bin AB Munawwar Aqsa A Sarfraz Zouina Z Sarfraz Azza A Robles-Velasco Karla K Cherrez-Ojeda Ivan I

Life (Basel, Switzerland) 20221220 1

Nearly 35 million people worldwide live with Alzheimer's disease (AD). The prevalence of the disease is expected to rise two-fold by 2050. With only symptomatic treatment options available, it is essential to understand the developments and existing evidence that aims to target brain pathology and dementia outcomes. This scoping systematic review aimed to collate existing evidence of CT1812 for use in patients with AD and summarize the methodologies of ongoing trials. Adhering to PRISMA Statemen ...[more]

PMID: 36675950

Similar Datasets

Project description:BACKGROUND:Alzheimer's disease is characterized by the deposition of amyloid-beta (Aβ) plaques in the brain. Aβ is produced from the sequential cleavage of amyloid precursor protein by β-site amyloid precursor protein-cleaving enzyme 1 (BACE-1) followed by γ-secretase. Verubecestat is an oral BACE-1 inhibitor that reduces the Aβ level in the cerebrospinal fluid of patients with Alzheimer's disease. METHODS:We conducted a randomized, double-blind, placebo-controlled, 78-week trial to evaluate verubecestat at doses of 12 mg and 40 mg per day, as compared with placebo, in patients who had a clinical diagnosis of mild-to-moderate Alzheimer's disease. The coprimary outcomes were the change from baseline to week 78 in the score on the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog; scores range from 0 to 70, with higher scores indicating worse dementia) and in the score on the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory scale (ADCS-ADL; scores range from 0 to 78, with lower scores indicating worse function). RESULTS:A total of 1958 patients underwent randomization; 653 were randomly assigned to receive verubecestat at a dose of 12 mg per day (the 12-mg group), 652 to receive verubecestat at a dose of 40 mg per day (the 40-mg group), and 653 to receive matching placebo. The trial was terminated early for futility 50 months after onset, which was within 5 months before its scheduled completion, and after enrollment of the planned 1958 patients was complete. The estimated mean change from baseline to week 78 in the ADAS-cog score was 7.9 in the 12-mg group, 8.0 in the 40-mg group, and 7.7 in the placebo group (P=0.63 for the comparison between the 12-mg group and the placebo group and P=0.46 for the comparison between the 40-mg group and the placebo group). The estimated mean change from baseline to week 78 in the ADCS-ADL score was -8.4 in the 12-mg group, -8.2 in the 40-mg group, and -8.9 in the placebo group (P=0.49 for the comparison between the 12-mg group and the placebo group and P=0.32 for the comparison between the 40-mg group and the placebo group). Adverse events, including rash, falls and injuries, sleep disturbance, suicidal ideation, weight loss, and hair-color change, were more common in the verubecestat groups than in the placebo group. CONCLUSIONS:Verubecestat did not reduce cognitive or functional decline in patients with mild-to-moderate Alzheimer's disease and was associated with treatment-related adverse events. (Funded by Merck; ClinicalTrials.gov number, NCT01739348 .).

Dataset Information

The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review.

Publications

The Allosteric Antagonist of the Sigma-2 Receptors-Elayta (CT1812) as a Therapeutic Candidate for Mild to Moderate Alzheimer's Disease: A Scoping Systematic Review.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets