Evidence map›Paper›PMID 39422941›Full record

ArticleJournal of Alzheimer's disease : JAD2024

Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer's Disease.

Howard H Feldman, Karen Messer, Yuqi Qiu, Marwan Sabbagh, Douglas Galasko, R Scott Turner, Oscar Lopez, Amanda Smith, January Durant, Jody-Lynn Lupo and 11 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03919162 (A Phase 2A Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Varoglutamstat), which is not on this map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
–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.

NCT03919162 phase2terminatednot on this map

A Phase 2A Randomized Double-Blind Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Varoglutamstat (PQ912) in Patients With Early Alzheimer's Disease With a Stage-Gate to Phase 2B (VIVA-MIND)

TypeinterventionalSponsorVivoryon Therapeutics N.V.Ran2021 to 2024Enrolled112ConditionsAlzheimer DiseaseArmsPQ912, Placebo
3 · Its place in the literature

Who cites it

12 citing papers in PubMed.

  1. Trial
  2. Review
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  4. Article
  5. Review
  6. Advances in the treatment of Alzheimer's disease.Frontiers in pharmacology · 2026
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. 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

21 authors.

Howard H FeldmanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Karen MesserDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Yuqi QiuDepartment of Statistics, East China Normal University, Shanghai, China.
Marwan SabbaghDepartment of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
Douglas GalaskoDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
R Scott TurnerDepartment of Neurology, Georgetown University, Washington, DC, USA.
Oscar LopezDepartment of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.
Amanda SmithUSF Health Byrd Alzheimer's Institute, Tampa, FL, USA.
January DurantDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Jody-Lynn LupoDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Carolyn RevtaDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Archana BalasubramanianDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Kerstin Kuehn-WacheVivoryon Therapeutics NV, Halle, Germany.
Tanja WassmannVivoryon Therapeutics NV, Halle, Germany.
Sylvia Schell-MaderVivoryon Therapeutics NV, Halle, Germany.
Diane M JacobsDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
David P SalmonDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Gabriel LégerDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Mari L DeMarcoDepartment of Pathology and Laboratory Medicine, Providence Health Care, Vancouver, BC, Canada.
Frank WeberVivoryon Therapeutics NV, Halle, Germany.
ADCS VIVA-MIND Study Group

Funding

UCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark W Bondi · 2019 to 2026
$34.9M
A Seamless Phase 2A-B Randomized Double Blind Placebo Controlled Trial to Evaluate the Efficacy and Safety of PQ 912 in Patients with Early Alzheimer's DiseaseR01AG061146 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2019 to 2023
$16.2M
NIA NIH HHS P30 AG062429NIA NIH HHS R01 AG061146
6 · The paper itself

Abstract

Background: Varoglutamstat is a first-in-class, small molecule being investigated as a treatment for early Alzheimer's disease (AD). It is an inhibitor of glutaminyl cyclase (QC), the enzyme that post-translationally modifies amyloid-β (Aβ) peptides into a toxic form of pyroglutamate Aβ (pGlu-Aβ) and iso-QC which post-translationally modifies cytokine monocyte chemoattractant protein-1 (CCL2) into neuroinflammatory pGlu-CCL2. Early phase clinical trials identified dose margins for safety and tolerability of varoglutamstat and biomarker data supporting its potential for clinical efficacy in early AD. Objective: Present the scientific rationale of varoglutamstat in the treatment of early AD and the methodology of the VIVA-MIND (NCT03919162) trial, which uses a seamless phase 2A-2B design. Our review also includes other pharmacologic approaches to pGlu-Aβ. Methods: Phase 2A of the VIVA-MIND trial will determine the highest dose of varoglutamstat that is safe and well tolerated with sufficient plasma exposure and a calculated target occupancy. Continuous safety evaluation using a pre-defined safety stopping boundary will help determine the highest tolerated dose that will carry forward into phase 2B. An interim futility analysis of cognitive function and electroencephalogram changes will be conducted to inform the decision of whether to proceed with phase 2B. Phase 2B will assess the efficacy and longer-term safety of the optimal selected phase 2A dose through 72 weeks of treatment. Conclusions: Varoglutamstat provides a unique dual mechanism of action addressing multiple pathogenic contributors to the disease cascade. VIVA-MIND provides a novel and efficient trial design to establish its optimal dosing, safety, tolerability, and efficacy in early AD.

Indexed as

Alzheimer DiseaseAminoacyltransferasesAgedAmyloid beta-PeptidesClinical Trials, Phase II as TopicFemaleHumansMaleRandomized Controlled Trials as TopicAminoacyltransferasesAmyloid beta-Peptidesglutaminyl-peptide cyclotransferaseAlzheimer’s diseaseamyloid β-peptidesCCL2cerebrospinal fluidglutaminyl cyclasemild cognitive impairmentN3pE-AβpGlu-AβQPCTQPCTL

Identifiers

PMID39422941
PMCPMC11494639

What OpenQuestion holds

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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 OpenQuestion graph.