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

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

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 r...

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Main Authors: E. G. B. Vijverberg, T. M. Axelsen, A. R. Bihlet, K. Henriksen, F. Weber, K. Fuchs, J. E. Harrison, K. Kühn-Wache, P. Alexandersen, N. D. Prins, Philip Scheltens
Format: Article
Language:English
Published: BMC 2021-08-01
Series:Alzheimer’s Research & Therapy
Subjects:
Alzheimer
Clinical trials; Small molecules; Puroglutamate
Abeta
Placebo
Amyloid
Online Access:https://doi.org/10.1186/s13195-021-00882-9
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spelling doaj-5e794479e452488bbaeb0ed21e24caf22021-08-29T11:42:51ZengBMCAlzheimer’s Research & Therapy1758-91932021-08-011311810.1186/s13195-021-00882-9Rationale 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—VIVIADE. G. B. Vijverberg0T. M. Axelsen1A. R. Bihlet2K. Henriksen3F. Weber4K. Fuchs5J. E. Harrison6K. Kühn-Wache7P. Alexandersen8N. D. Prins9Philip Scheltens10Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMCDepartment of Biomedical Sciences, Faculty of Health and Medical Sciences, University of CopenhagenNBCD A/SVivoryon Therapeutics NVVivoryon Therapeutics NVVivoryon Therapeutics NVAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMCVivoryon Therapeutics NVSanos Clinic A/SAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMCAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMCAbstract 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: NCT04498650https://doi.org/10.1186/s13195-021-00882-9AlzheimerClinical trials; Small molecules; PuroglutamateAbetaPlaceboAmyloid
collection DOAJ
language English
format Article
sources DOAJ
author E. G. B. Vijverberg
T. M. Axelsen
A. R. Bihlet
K. Henriksen
F. Weber
K. Fuchs
J. E. Harrison
K. Kühn-Wache
P. Alexandersen
N. D. Prins
Philip Scheltens
spellingShingle E. G. B. Vijverberg
T. M. Axelsen
A. R. Bihlet
K. Henriksen
F. Weber
K. Fuchs
J. E. Harrison
K. Kühn-Wache
P. Alexandersen
N. D. Prins
Philip Scheltens
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
Alzheimer’s Research & Therapy
Alzheimer
Clinical trials; Small molecules; Puroglutamate
Abeta
Placebo
Amyloid
author_facet E. G. B. Vijverberg
T. M. Axelsen
A. R. Bihlet
K. Henriksen
F. Weber
K. Fuchs
J. E. Harrison
K. Kühn-Wache
P. Alexandersen
N. D. Prins
Philip Scheltens
author_sort E. G. B. Vijverberg
title 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
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
publisher BMC
series Alzheimer’s Research & Therapy
issn 1758-9193
publishDate 2021-08-01
description 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
topic Alzheimer
Clinical trials; Small molecules; Puroglutamate
Abeta
Placebo
Amyloid
url https://doi.org/10.1186/s13195-021-00882-9
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