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Randomized Controlled Trial
. 2021 Aug 23;13(1):142.
doi: 10.1186/s13195-021-00882-9.

Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD-VIVIAD

E G B Vijverberg #  1   2 , T M Axelsen #  3   4 , A R Bihlet  5 , K Henriksen  6 , F Weber  6 , K Fuchs  6 , J E Harrison  1   7   8 , K Kühn-Wache  6 , P Alexandersen  4 , N D Prins  1   2 , Philip Scheltens  9   10
Affiliations
Randomized Controlled Trial

Rationale and study design of a randomized, placebo-controlled, double-blind phase 2b trial to evaluate efficacy, safety, and tolerability of an oral glutaminyl cyclase inhibitor varoglutamstat (PQ912) in study participants with MCI and mild AD-VIVIAD

E G B Vijverberg et al. Alzheimers Res Ther. .

Abstract

Background: Varoglutamstat (formerly PQ912) is a small molecule that inhibits the activity of the glutaminyl cyclase to reduce the level of pyroglutamate-A-beta (pGluAB42). Recent studies confirm that pGluAB42 is a particular amyloid form that is highly synaptotoxic and plays a significant role in the development of AD.

Methods: This paper describes the design and methodology behind the phase 2b VIVIAD-trial in AD. The aim of this study is to evaluate varoglutamstat in a state-of-the-art designed, placebo-controlled, double-blind, randomized clinical trial for safety and tolerability, efficacy on cognition, and effects on brain activity and AD biomarkers. In addition to its main purpose, the trial will explore potential associations between novel and established biomarkers and their individual and composite relation to disease characteristics.

Results: To be expected early 2023 CONCLUSION: This state of the art phase 2b study will yield important results for the field with respect to trial methodology and for the treatment of AD with a small molecule directed against pyroglutamate-A-beta.

Trial registration: ClinicalTrials.gov Identifier: NCT04498650.

Keywords: Abeta; Alzheimer; Amyloid; Clinical trials; Small molecules; Puroglutamate; Placebo.

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Conflict of interest statement

Dr. Scheltens has received consultancy fees (paid to the institution) from AC Immune, Alkermes, Alnylam, Alzheon, Anavex, Biogen, Brainstorm Cell, Cortexyme, Denali, EIP, ImmunoBrain Checkpoint, GemVax, Genentech, Green Valley, Novartis, Novo Nordisk, PeopleBio, Renew LLC, and Roche. He is PI of studies with AC Immune, CogRx, FUJI-film/Toyama, IONIS, UCB, and Vivoryon. He is a part-time employee of Life Sciences Partners Amsterdam. He serves on the board of the Brain Research Center.

Dr. Vijverberg has received consultancy fees (paid to the institution) from Biogen, Brainstorm Cell, ImmunoBrain Checkpoint, New Amsterdam Pharma, and Treeway. He is PI of studies with AC Immune, CogRx, Green Valley, IONIS, Janssen, Roche, Rodin Therapeutics, Sanofi, UCB, and Vivoryon.

Dr. Harrison has received consultancy fees from 23andMe, Alkahest, AlzeCure, Aptinyx, Athira Pharma, Axon, Axovant, Bial, Biogen, BlackthornRx, Boehringer Ingelheim, Brands2Life, Cognition Therapeutics, Compass Pathways, Corlieve, Cronos, Curasen, DeNDRoN, Eisai, EIP Pharma, Eli Lilly, FSV7, G4X Discovery, GfHEU, Heptares, Imperial College, Johnson & Johnson, Kaasa Health, Ki-Elements, Lundbeck, Lysosome Therapeutics, Merck, Neurocentria, Neurocog, Neurodyn, Neurotrack, NHS, Novartis, Nutricia, Probiodrug, Regeneron, reMYND, Rodin Therapeutics, Roivant, Samumed, Sanofi, Signant Health, Syndesi Therapeutics, Takeda, Virusgenics, Vivoryon, and WinterLight Labs.

Dr. Axelsen has no conflicts of interest to declare.

Dr. Weber is a part-time employee of Vivoryon Therapeutics NV, Germany.

AR. Bihlet is a full-time employee of NBCD A/S, a clinical contract-research organization.

K. Kuehn-Wache and K. Fuchs are a full-time employees of Vivoryon Therapeutics NV, Germany.

Dr. Prins is consultant to Boehringer Ingelheim and Aribio. He is co-PI of studies with EIP Pharma and Fuji Film Toyama Chemical. He serves on the DSMB of Abbvie’s M15-566 trial. He is CEO and co-owner of the Brain Research Center, The Netherlands.

Figures

Fig. 1
Fig. 1
Overview of study design. Coding test, WAIS-IV coding test; MMSE, Mini Mental State Examination; NTB, Neuropsychological Test Battery; WLA, Winterlight Language Assessment; A-IADL-Q, Amsterdam Instrumental of Activities of Daily Living Questionnaire
Fig. 2
Fig. 2
Conceptual figure denoting statistical approach to incorporate the variable treatment times of the enrolled study participants in the data analysis
See this image and copyright information in PMC

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