A Trial to Evaluate the Efficacy and Safety of PQ912 in Patients With Early AD

Summary

This is a Phase 2A multi-center, randomized, double blind, placebo-controlled, parallel group study of varoglutamstat, with a stage gate to Phase 2B. In Phase 2A there will be adaptive dosing evaluation of three dose levels with exposure to varoglutamstat or placebo for a minimum of 24 weeks, with preliminary evaluation of both cognitive function and pharmacodynamic changes on EEG spectral analysis in approximately 180 participants. In the event that the stage gate for Phase 2B is reached, then Phase 2B will assesses efficacy and longer-term safety in a larger study group, i.e., 414.

Timeline

Start

2021-11-15

Primary completion

2024-07-12

Completion

2024-08-12

Outcome

Missed primary endpoint

Stopped (Business): “It has been made the strategic decision to terminate the study. This decision to terminate the study early is not being made for safety reasons.”

registry analysis (superiority test); PQ912 vs Placebo; p = 0.2261; Difference LS Mean 0.058 (95% CI -0.036 to 0.152) NCT03919162 ↗

registry analysis (superiority test); PQ912 vs Placebo; p = 0.4814; Difference LS Mean -0.00526 (95% CI -0.02017 to 0.00964) NCT03919162 ↗

registry analysis (superiority test); PQ912 vs Placebo; p = 0.9135; Difference LS Mean -0.05 (95% CI -1.03 to 0.92) NCT03919162 ↗

release “VIVIAD Phase 2b study did not meet its primary and key secondary endpoints” vivoryon.com ↗

Publications

• Background Feldman HH, Messer K, Qiu Y, Sabbagh M, Galasko D, Turner RS, Lopez O, Smith A, Durant J, Lupo JL, Revta C, Balasubramanian A, Kuehn-Wache K, Wassmann T, Schell-Mader S, Jacobs DM, Salmon DP, Leger G, DeMarco ML, Weber F; ADCS VIVA-MIND Study Group. Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer's Disease. J Alzheimers Dis. 2024;101(s1):S79-S93. doi: 10.3233/JAD-231126.
• Background Messer K, Jacobs DM, Salmon DP, Qiu Y, Revta C, Weber F, Kuhn-Wache K, Leger GC, Feldman HH. (2022), A novel, efficient and seamless Phase 2A-2B design to test varoglutamstat in early AD: the VIVAMIND study. Alzheimer's Dement., 18(S10): e065197.
• Background Lues I, Weber F, Meyer A, Buhring U, Hoffmann T, Kuhn-Wache K, Manhart S, Heiser U, Pokorny R, Chiesa J, Glund K. A phase 1 study to evaluate the safety and pharmacokinetics of PQ912, a glutaminyl cyclase inhibitor, in healthy subjects. Alzheimers Dement (N Y). 2015 Oct 3;1(3):182-195. doi: 10.1016/j.trci.2015.08.002. eCollection 2015 Nov.
• Background Scheltens P, Hallikainen M, Grimmer T, Duning T, Gouw AA, Teunissen CE, Wink AM, Maruff P, Harrison J, van Baal CM, Bruins S, Lues I, Prins ND. Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimers Res Ther. 2018 Oct 12;10(1):107. doi: 10.1186/s13195-018-0431-6.
• Results Feldman HH, Messer K, Zhang J, Quach NE, Léger GC, Jacobs DM, Edland SD, Duehring J, MacKelfresh A, Pol A, Revta C, Lupo JL, Balasubramanian A, Lama N, Wassmann T, Schaeffer M, Hoffmann T, Meyer A, Schell-Mader S, Wenzkowski C, Weber F, for the ADCS VIVA-MIND Study Group. The VIVA-MIND study: Topline Results from Phase 2 RCT of Varoglutamstat in Early AD. In press, abstract at 2025 AAIC, Alzheimer's and Dementia

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	PQ912	Small molecule	150 mg	Oral
Subject	PQ912	Small molecule	300 mg	Oral
Subject	PQ912	Small molecule	600 mg	Oral

Indications