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

Primary Purpose

Alzheimer Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PQ912
Placebo
Sponsored by
Vivoryon Therapeutics N.V.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Disease focused on measuring Alzheimer's Disease, Mild Cognitive Impairment, Mild Alzheimer's Disease, Early Alzheimer's disease, MCI

Eligibility Criteria

50 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Banner Sun Health Research InstituteRecruiting
  • The Neuron ClinicRecruiting
  • University of CaliforniaRecruiting
  • UCSD Alzheimer's Disease Research CenterRecruiting
  • Cedars-Sinai CenterRecruiting
  • PCND NeurologyRecruiting
  • Georgetown University Medical CenterRecruiting
  • USF Health Byrd Alzheimer's Center and Research InstituteRecruiting
  • Emory UniversityRecruiting
  • Northwestern University Feinberg School of MedicineRecruiting
  • The University of Iowa Carver College of MedicineRecruiting
  • The University of Kentucky Sanders-Brown Center on AgingRecruiting
  • Northern Light Acadia HospitalRecruiting
  • NYU Langone Health Tisch HospitalRecruiting
  • SUNY Upstate Medical UniversityRecruiting
  • Ohio State UniversityRecruiting
  • OHSU Neurology ClinicRecruiting
  • Abington Neurological AssociatesRecruiting
  • Rhode Island HospitalRecruiting
  • Lowcountry Center for Veterans Research (LCVR)Recruiting
  • UT Health San AntonioRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

600 mg

300 mg

150 mg

Placebo

Arm Description

First 4 weeks 150 mg BID, week 5-8 300 mg BID, week 9-24 600 mg BID

First 4 weeks 150 mg BID, week 5-24 300 mg BID

24 weeks on 150 mg BID

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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

Secondary Outcome Measures

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.

Full Information

First Posted
April 15, 2019
Last Updated
October 18, 2023
Sponsor
Vivoryon Therapeutics N.V.
Collaborators
Alzheimer's Disease Cooperative Study (ADCS), National Institute on Aging (NIA)
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1. Study Identification

Unique Protocol Identification Number
NCT03919162
Brief Title
A Trial to Evaluate the Efficacy and Safety of PQ912 in Patients With Early AD
Acronym
VIVA-MIND
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 15, 2021 (Actual)
Primary Completion Date
November 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vivoryon Therapeutics N.V.
Collaborators
Alzheimer's Disease Cooperative Study (ADCS), National Institute on Aging (NIA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Disease
Keywords
Alzheimer's Disease, Mild Cognitive Impairment, Mild Alzheimer's Disease, Early Alzheimer's disease, MCI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
414 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
600 mg
Arm Type
Experimental
Arm Description
First 4 weeks 150 mg BID, week 5-8 300 mg BID, week 9-24 600 mg BID
Arm Title
300 mg
Arm Type
Experimental
Arm Description
First 4 weeks 150 mg BID, week 5-24 300 mg BID
Arm Title
150 mg
Arm Type
Experimental
Arm Description
24 weeks on 150 mg BID
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
PQ912
Other Intervention Name(s)
Varoglutamstat
Intervention Description
PQ912 150 mg tablets
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo tablets to mimic PQ912 150 mg tablets
Primary Outcome Measure Information:
Title
2A Primary safety: proportion of participants who experience any adverse event of interest (AE-I).
Description
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.
Time Frame
24 weeks
Title
2A Primary PK: derived mean values of varoglutamstat levels and corresponding calculated target occupancy (TO)
Description
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.
Time Frame
24 weeks
Title
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.
Description
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.
Time Frame
24 weeks
Title
2A Primary efficacy:The within-participant change from baseline to week 24 in quantitative EEG (global relative theta wave power)
Description
The within-participant change frombaseline to week 24 of the global relative theta wave power (4-8 Hz) compared between active arm and placebo.
Time Frame
24 weeks
Title
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.
Description
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
Time Frame
72 weeks
Secondary Outcome Measure Information:
Title
Key secondary efficacy: CFC2, a cognitive-functional composite
Description
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.
Time Frame
72 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Archana Balasubramanian
Phone
+1 858-246-1277
Email
viva-mind@health.ucsd.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Tanja Wassmann
Phone
+49 345 5559900
Email
clinics@vivoryon.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Howard Feldman
Organizational Affiliation
Alzheimer's Disease Cooperative Study (ADCS)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Banner Sun Health Research Institute
City
Sun City
State/Province
Arizona
ZIP/Postal Code
85351
Country
United States
Individual Site Status
Recruiting
Facility Name
The Neuron Clinic
City
Chula Vista
State/Province
California
ZIP/Postal Code
91910
Country
United States
Individual Site Status
Recruiting
Facility Name
University of California
City
Irvine
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
UCSD Alzheimer's Disease Research Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Individual Site Status
Recruiting
Facility Name
Cedars-Sinai Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Individual Site Status
Recruiting
Facility Name
PCND Neurology
City
Poway
State/Province
California
ZIP/Postal Code
92064
Country
United States
Individual Site Status
Recruiting
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20057
Country
United States
Individual Site Status
Recruiting
Facility Name
USF Health Byrd Alzheimer's Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33613
Country
United States
Individual Site Status
Recruiting
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Name
Northwestern University Feinberg School of Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Iowa Carver College of Medicine
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Kentucky Sanders-Brown Center on Aging
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Individual Site Status
Recruiting
Facility Name
Northern Light Acadia Hospital
City
Bangor
State/Province
Maine
ZIP/Postal Code
04401
Country
United States
Individual Site Status
Recruiting
Facility Name
NYU Langone Health Tisch Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
SUNY Upstate Medical University
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Individual Site Status
Recruiting
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Name
OHSU Neurology Clinic
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Name
Abington Neurological Associates
City
Abington
State/Province
Pennsylvania
ZIP/Postal Code
19001
Country
United States
Individual Site Status
Recruiting
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Individual Site Status
Recruiting
Facility Name
Lowcountry Center for Veterans Research (LCVR)
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29403
Country
United States
Individual Site Status
Recruiting
Facility Name
UT Health San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes

Learn more about this trial

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

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