A Trial to Evaluate the Efficacy and Safety of PQ912 in Patients With Early AD (VIVA-MIND)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: PQ912; Other: Placebo

Detailed Description

The goal of this study is to advance a first-in-class, new small molecule treatment for early Alzheimer's disease (AD). Varoglutamstat (PQ912) is an oral, twice daily medication that addresses a novel and significantly differentiated amyloid target: N-terminal post-translationally modified Ab (pGlu-Ab), a particularly toxic subspecies of amyloid beta (Ab). This study will further evaluate whether varoglutamstat's mechanism of action can result in a measurable therapeutic effect on cognition, function and relevant pharmacodynamic and biological markers in early AD.

The study is a phase 2A multi-center, randomized, double-blind, parallel group trial, with a stage gate to phase 2B. Phase 2A will determine the highest dose that is both safe and well tolerated. During this phase, there is an adaptive dosing evaluation, using a well-defined safety stopping boundary, of three dose levels with exposure to varoglutamstat or placebo for a minimum of 24 weeks to help determine which dose will be carried forward in phase 2B. A sequential dose design will be employed in phase 2A where each of three dose cohorts are randomized equally to placebo or varoglutamstat and treated for at least 8 weeks at the originally assigned full dose. Participants will be randomized 1:1 to varoglutamstat or placebo, and stratified between mild AD and MCI, as well as by site.

Phase 2A also includes preliminary evaluation of both cognitive function and pharmacodynamics changes on electroencephalogram (EEG) spectral analysis.

In the event that the stage gate for phase 2B is reached from data in this phase 2A study, then phase 2B will assess the longer-term efficacy and safety of varoglutamstat in a larger study group, using the highest dose selected in phase 2A. In phase 2B, a composite cognitive and functional measure as well as PD biomarkers will be used to evaluate efficacy during the extended treatment period.

• Study Type: Interventional
• Enrollment (Estimated): 414
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Archana Balasubramanian; Phone Number: +1 858-246-1277; Email: viva-mind@health.ucsd.edu
• Study Contact Backup: Name: Tanja Wassmann; Phone Number: +49 345 5559900; Email: clinics@vivoryon.com

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Recruiting
      • Barrow Neurological Institute
    • Sun City, Arizona, United States, 85351
      • Recruiting
      • Banner Sun Health Research Institute
  • California
    • Chula Vista, California, United States, 91910
      • Recruiting
      • The Neuron Clinic
    • Irvine, California, United States, 92868
      • Recruiting
      • University of California
    • La Jolla, California, United States, 92037
      • Recruiting
      • UCSD Alzheimer's Disease Research Center
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Center
    • Poway, California, United States, 92064
      • Recruiting
      • PCND Neurology
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Recruiting
      • Georgetown University Medical Center
  • Florida
    • Tampa, Florida, United States, 33613
      • Recruiting
      • USF Health Byrd Alzheimer's Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern University Feinberg School of Medicine
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • The University of Iowa Carver College of Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Recruiting
      • The University of Kentucky Sanders-Brown Center on Aging
  • Maine
    • Bangor, Maine, United States, 04401
      • Recruiting
      • Northern Light Acadia Hospital
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health Tisch Hospital
    • Syracuse, New York, United States, 13210
      • Recruiting
      • SUNY Upstate Medical University
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • OHSU Neurology Clinic
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Recruiting
      • Abington Neurological Associates
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Recruiting
      • Lowcountry Center for Veterans Research (LCVR)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • UT Health San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Age 50-89 (inclusive) at screening
• Diagnosed as having Mild Cognitive Impairment (MCI) due to Alzheimer's disease (AD) or Mild probable AD according to workgroups of the Diagnostic Guidelines of the National Institute on Aging and Alzheimer's Association (NIA-AA)
• Mini-Mental State Examination (MMSE) score 20-30 inclusive at screening
• Montreal Cognitive Assessment score (MoCA) < 26 at screening
• Clinical Dementia Rating global score 0.5 or 1 with memory score of > 0.5 at screening
• Positive CSF AD biomarker signature
• A brain MRI scan within 6 months of screening consistent with a diagnosis of Alzheimer's disease
• Participants must have a study partner who has frequent interaction with them (approximately >3-4 times per week), will be present for all clinic visits, and can assist in compliance with study procedures.

Key Exclusion Criteria:

• • Significant neurodegenerative diseases and causes of dementia, other than AD, including Parkinson's disease and Huntington's disease, vascular dementia, CJD (Creutzfeldt-Jakob disease), LBD (Lewy Body dementia), PSP (Progressive Supranuclear Palsy), AIDS (Acquired Immunodeficiency Syndrome), or NPH (normal pressure hydrocephalus)
• Meeting Diagnostic Criteria for Possible AD according to workgroups of the Diagnostic Guidelines of the NIA-AA
• Hepatic impairment defined as Child-Pugh class A or more severe liver impairment
• History of moderate or severe skin reactions to medications or current moderate or severe disease of the skin and subcutaneous tissues
• History of a major depressive episode within the past 6 months of screening
• History of diagnosis of schizophrenia
• History of uncontrolled bipolar disorder within past five years of screening
• History of seizures within past two years of screening
• Contraindication to lumbar puncture and MRI
• Participation in another clinical trial for an investigational agent and having taken at least one dose of study drug, unless confirmed as having been on placebo, within 90 days prior to the baseline visit. The end of a previous investigational trial is defined as the date of the last dose of an investigational agent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo tablets to mimic PQ912 150 mg tablets
Experimental: 600 mg; First 4 weeks 150 mg BID, week 5-8 300 mg BID, week 9-24 600 mg BID	Drug: PQ912; PQ912 150 mg tablets; Other Names: Varoglutamstat
Experimental: 300 mg; First 4 weeks 150 mg BID, week 5-24 300 mg BID	Drug: PQ912; PQ912 150 mg tablets; Other Names: Varoglutamstat
Experimental: 150 mg; 24 weeks on 150 mg BID	Drug: PQ912; PQ912 150 mg tablets; Other Names: Varoglutamstat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2A Primary safety: proportion of participants who experience any adverse event of interest (AE-I).	The primary endpoint in phase 2A is the proportion of participants, for each dose, who experience any adverse event of interest (AE-I) during the safety reporting period, from first dose to completion of 8 weeks at the full originally assigned dose.	24 weeks
2A Primary PK: derived mean values of varoglutamstat levels and corresponding calculated target occupancy (TO)	The pharmacokinetics (PK) endpoints in Phase 2A are the derived mean values of varoglutamstat levels in plasma and the correspondingcalculated TO in CSF, for each dose.	24 weeks
2A Primary efficacy: The within-participant change from baseline to week 24 in the composite sum of standardized scores from the ADNI Battery Composite (ABC, 9-item) compared between active arm and placebo.	The ABC is a set of ADNI neuropsychological test measures, including: Category Fluency (Animals and Vegetables), Trail Making A and B, Digit Symbol Substitution, Boston Naming Test, Rey's Auditory and Verbal Learning Test (RAVLT, Immediate and Delayed), Digit Span Forward and Backward.	24 weeks
2A Primary efficacy:The within-participant change from baseline to week 24 in quantitative EEG (global relative theta wave power)	The within-participant change frombaseline to week 24 of the global relative theta wave power (4-8 Hz) compared between active arm and placebo.	24 weeks
2B Primary efficacy: The within-participant change from baseline to week 72 in the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) score, compared between active arm and placebo.	The CDR-SB evaluates cognition and everyday functioning incorporating both informant input and direct assessment of performance. It is scored on a five-point scale a five point scale with following five possible scores: 0 = Normal 0.5 = Very Mild Dementia; = Mild Dementia; = Moderate Dementia; = Severe Dementia	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Key secondary efficacy: CFC2, a cognitive-functional composite	The key secondary objective in phase 2B is to evaluate the efficacy of PQ912 as measured by CFC2, a cognitive-functional composite, over a 72-week treatment period.	72 weeks

Collaborators and Investigators

• Sponsor: Vivoryon Therapeutics N.V.
• Collaborators: National Institute on Aging (NIA); Alzheimer's Disease Cooperative Study (ADCS)
• Investigators: Principal Investigator: Howard Feldman, Alzheimer's Disease Cooperative Study (ADCS)

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Estimated): November 30, 2023
• Study Completion (Estimated): November 30, 2023

Study Registration Dates

• First Submitted: April 15, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): November 2, 2023
• Last Update Submitted That Met QC Criteria: November 1, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Mild Cognitive Impairment; MCI; Mild Alzheimer's Disease; Early Alzheimer's disease
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: PBD-01187; 1R01AG061146-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No