Evidence mapPaperPMID 39166791Full record

SynthesisAlzheimer's & dementia : the journal of the Alzheimer's Association2024

CT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.

Britney N Lizama, Claire Williams, Hilary A North, Kiran Pandey, Duc Duong, Valentina Di Caro, Adam P Mecca, Kaj Blennow, Henrik Zetterberg, Allan I Levey and 5 more

2 registry-linked trialsAbstract readMeta-AnalysisClinical Trial, Phase II
In one paragraph

Synthesis in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03493282 phase1 / phase2completednot on this map

A Pilot Synaptic Vesicle Glycoprotein 2A (SV2A) PET Study to Evaluate the Effect of CT1812 Treatment on Synaptic Density in Participants With Mild to Moderate Alzheimer's Disease

TypeinterventionalSponsorCognition TherapeuticsRan2018 to 2020Enrolled43ConditionsAlzheimer DiseaseArmsActive Treatment- CT1812 100 mg, Active Treatment- CT1812 300 mg, Placebo
NCT03507790 phase2completednot on this map

A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase 2 Study to Evaluate the Safety and Efficacy of CT1812 in Subjects With Mild to Moderate Alzheimer's Disease.

TypeinterventionalSponsorCognition TherapeuticsRan2018 to 2024Enrolled153ConditionsMild to Moderate Alzheimer's DiseaseArmsCT1812, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. The roles of biomarkers in Alzheimer's disease clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Britney N LizamaCognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Claire WilliamsCognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Hilary A NorthCognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Kiran PandeyEmtherapro Inc, Systems Biology, Atlanta, Georgia, USA.
Duc DuongEmory University School of Medicine, Biochemistry, Atlanta, Georgia, USA.
Valentina Di CaroCognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Adam P MeccaDepartment of Psychiatry, Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA.
Kaj BlennowParis Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris, France.
Henrik ZetterbergDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Göteborg, Sweden.
Allan I LeveyEmory University School of Medicine, Neurology, Atlanta, Georgia, USA.
Michael GrundmanGlobal R&D Partners, LLC, San Diego, California, USA.
Christopher H van DyckDepartment of Psychiatry, Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA.
Anthony O CaggianoCognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Nicholas T SeyfriedEmory University School of Medicine, Biochemistry, Atlanta, Georgia, USA.
Mary E HambyCognition Therapeutics, Pittsburgh, Pennsylvania, USA.ORCID 0000-0002-6782-1853

Funding

Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
The Goizueta Alzheimer's Disease Research CenterP30AG066511 · EMORY UNIVERSITY · 2025 to 2025
$4.5M
Alzheimer's Drug Discovery FoundationEuropean Union's Horizon Europe research and innovation programme 101053962NCATS NIH HHS UL1 TR001863NIA NIH HHS 1R01AG058660-01NIA NIH HHS P30 AG066511NIA NIH HHS R01 AG058660NIA NIH HHS RF1 AG057553NIA NIH HHS RF1AG057553Swedish Research Council #2019-02397Swedish Research Council #2022-01018Swedish Research Council #2023-00356Swedish State Support for Clinical Research #ALFGBG-71320
6 · The paper itself

Abstract

introductionCT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.

methodsUnbiased analysis of tandem-mass tag mass spectrometry (TMT-MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282). Comparative analyses and a meta-analysis with the interim SHINE cohort (NCT03507790; SHINE-A) followed by network analysis (weighted gene co-expression network analysis [WGCNA]) were used to understand the biological impact of CT1812.

resultsCT1812 pharmacodynamic biomarkers and biological pathways were identified that replicate across two clinical cohorts. The meta-analysis revealed novel candidate biomarkers linked to S2R biology and AD, and network analysis revealed treatment-associated networks driven by S2R.  DISCUSSION: Early clinical validation of CT1812 candidate biomarkers replicating in independent cohorts strengthens the understanding of the biological impact of CT1812 in patients with AD, and supports CT1812's synaptoprotective mechanism of action and its continued clinical development. HIGHLIGHTS: This exploratory proteomics study identified candidate biomarkers of CT1812 in SPARC (NCT03493282) Comparative analyses identified biomarkers replicating across trials/cohorts Two independent Ph2 trial cohorts (SPARC and interim SHINE [NCT03507790; SHINE-A]) were used in a meta-analysis Amyloid beta (Aβ) & synaptic biology impacted by CT1812 and volumetric magnetic resonance imaging (vMRI) treatment-related correlates emerge Network analyses revealed sigma-2 receptor (S2R)-interacting proteins that may be "drivers" of changes.

Indexed as

Alzheimer DiseaseBiomarkersProteomicsAgedAmyloid beta-PeptidesCohort StudiesFemaleHumansMagnetic Resonance ImagingMaleAmyloid beta-PeptidesBiomarkersAlzheimer's diseaseAβ oligomersclinical trialCSF pharmacodynamic biomarkersCT1812investigational therapeuticTMT‐MS proteomics

Identifiers

PMID39166791
PMCPMC11485314

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.