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 role in the development of AD. Methods:This paper describes the design and methodology behind the VIVIAD-trial. The aim of this study is to evaluate varoglutamstat in a state-of-the-art phase 2b, placebo-controlled, double-blind, randomized clinical trial on safety and tolerability, efficacy on cognition, 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 2023Conclusion: This state of the art phase 2b study will yield important results for the field and the treatment of AD with a small molecule directed against pyroglutamate-A-beta.

Pyroglutamate Aβ cascade as drug target in Alzheimer’s disease

“…PQ912, a competitive inhibitor of QC, was analyzed in clinical trials in order to assess the safety, pharmacokinetics, and pharmacodynamics in healthy individuals [53], MCI and AD patients [54,55] and was reported to be safe. QC-dependent blood biomarker levels were significantly altered by treatment with PQ912.…”