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A Study to Evaluate Safety and Tolerability of Different Doses and Efficacy of PQ912 in Subjects With MCI and Mild AD (VIVIAD)

Primary Purpose

Early Alzheimers Disease, Mild Cognitive Impairment Due to AD

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

PQ912

Placebo

About this trial

This is an interventional treatment trial for Early Alzheimers Disease

Eligibility Criteria

50 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

Positive CSF AD biomarker signature according to the AA-NIA criteria
Clinical syndrome of MCI or mild dementia according to the AA-NIA Research Framework
A cognitive impairment in the WAIS IV Coding Test of at least 0.5 standard deviation below the normative data
Adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the investigator
Meeting the completion and performance criteria for the CogState NTB
Outpatient with study partner capable of accompanying the subject on all applicable clinic visits

Main Exclusion Criteria:

Significant neurological or psychiatric disorders, other than AD, that may affect cognition.
Atypical clinical presentations of MCI due to AD or mild dementia due to AD, such as the visual variant of AD (including posterior cortical atrophy), frontal variant or the language variant (including logopenic aphasia).
Moderate and severe dementia with a Mini-Mental State Examination score (MMSE) below 20.
Current presence of a clinically important major psychiatric disorder (e.g. major depressive disorder) as defined by DSM-5 criteria, or symptom(s) (e.g. hallucinations) that could affect the subject's ability to complete the study.
History of clinically evident stroke.
History of seizures within the last two years prior to the screening visit.
Myocardial infarction within the last six months prior to screening.
History of uncontrolled hypertension (in the opinion of the investigator) within six months prior to screening.
Contraindication to lumbar puncture and MRI

Sites / Locations

Sanos Clinics
Sanos Clinics
Sanos Clinics
Charité - Universitätsmedizin Berlin
Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie
Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung
Institut für Studien zur Psychischen Gesundheit (ISPG)
Klinikum rechts der Isar der TU München / Klinik für Psychiatrie und Psychotherapie
Universitätsklinikum Münster / Klinik für Allgemeine Neurologie
Klinik für Neurologie Universitätsklinikum Ulm
Brain Research Center
Brain Research Center
Brain Research Center Zwolle
Podlaskie Centrum
SOMED CR
SOMED CR
Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych Uniwersytetu Medycznego w Łodzi
Neurology (Memory Unit) - Hospital de la Santa Creu i Sant Pau
Fundació ACE
Cae Oroitu
Unidad de Neurociencias. Hospital Victoria Eugenia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

300 mg

600 mg

Arm Description

Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-24: 300 mg BID

Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-12: 300 mg BID Dose in weeks 12-24: 600 mg BID

Outcomes

Primary Outcome Measures

Primary safety: The proportion of participants who experience any Adverse Event (AE), Serious Adverse Event (SAE), Adverse Event of Interest (AE-I)

The safety analysis will include the number of subjects with, and the number of any AE, any SAE (both overall and related), AEs leading to discontinuation of treatment, AEs leading to temporary treatment interruption, treatment compliance, the number of subjects with AEs of interest as defined above, the severity, duration and outcome of AEs

Primary efficacy: within-participant linear change with time of the combinded z-score for cognition compared between active arm and placebo.

The within-participant change over time in cognition measured by the combined z-score of the Detection test, Identification test and the 'One Back' test (attention and working memory domains) of the Neurological Test Battery

Secondary Outcome Measures

Secondary efficacy: The within-participant linear change from baseline to week 48 in quantitative EEG (global relative theta wave power), compared between active and placebo.

Using a quantitative EEG the within-participant change from baseline to week 48 of the global relative theta wave power (4-8 Hz) will serve as a primary efficacy outcome.

Secondary efficacy: The within-participant linear change with time in overall cognition as measured by the CogState Brief Battery (CBB) Z-score compared between active arm and placebo

he within-participant linear change with time in overall cognition as measured by the CBB (CogState Detection, Identification, One Card Learning and One Back test) -Z-score

Full Information

NCT ID

NCT04498650

First Posted

July 21, 2020

Last Updated

September 14, 2023

Sponsor

Vivoryon Therapeutics N.V.

Collaborators

Nordic Bioscience A/S, Amsterdam UMC, location VUmc

1. Study Identification

Unique Protocol Identification Number

NCT04498650

Brief Title

A Study to Evaluate Safety and Tolerability of Different Doses and Efficacy of PQ912 in Subjects With MCI and Mild AD

Acronym

VIVIAD

Official Title

A Phase 2b Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel Group Dose Finding, Safety, Tolerability and Efficacy Study of PQ912 in Subjects With MCI and Mild Dementia Due to Alzheimer's Disease.

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

July 6, 2020 (Actual)

Primary Completion Date

January 2024 (Anticipated)

Study Completion Date

March 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Vivoryon Therapeutics N.V.

Collaborators

Nordic Bioscience A/S, Amsterdam UMC, location VUmc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a phase 2B multicenter, randomized, double-blind, placebo-controlled, parallel group dose finding study to evaluate the safety, tolerability and efficacy of PQ912, an inhibitor of the glutaminyl cyclase enzyme, in 250 subjects with mild cognitive impairment and mild dementia due to Alzheimer 's Disease.

Detailed Description

In the parallel group dose finding part of the study the first 90 subjects will be randomized 1:1:1 between PQ912 300 mg BID, 600 mg BID, and placebo. When the 90th patient has completed the week 24 treatment visit, the DSMB will decide on the dose of PQ912 to be continued. The decision is based on safety findings only, no efficacy data will be considered. After the DSMB has reached a decision on the dose to be continued, all subjects randomized to receive PQ912 will be reallocated to this dose (1:1). The duration of Subjects participation in the study is either 48, 60, 72, 84 or 96 weeks of treatment (depending on time of randomization). Subjects recruited early into the study will be kept on treatment for 96 weeks or until the regular, scheduled study visit which is closest to the scheduled week 48 visit of the last subject recruited in the study, whichever comes first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Early Alzheimers Disease, Mild Cognitive Impairment Due to AD

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

259 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

300 mg

Arm Type

Experimental

Arm Description

Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-24: 300 mg BID

Arm Title

600 mg

Arm Type

Experimental

Arm Description

Dose in weeks 1 and 2: 50 mg once daily (evening) Dose in weeks 3 and 4: 50 mg BID Dose in weeks 5-8: 150 mg BID Dose in weeks 9-12: 300 mg BID Dose in weeks 12-24: 600 mg BID

Intervention Type

Drug

Intervention Name(s)

PQ912

Other Intervention Name(s)

varoglutamstat

Intervention Description

PQ912 50 mg tablets and 150 mg tablets

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Placebo tablets to mimic PQ912 50 mg and 150 mg tablets

Primary Outcome Measure Information:

Title

Primary safety: The proportion of participants who experience any Adverse Event (AE), Serious Adverse Event (SAE), Adverse Event of Interest (AE-I)

Description

Time Frame

48 weeks

Title

Primary efficacy: within-participant linear change with time of the combinded z-score for cognition compared between active arm and placebo.

Description

Time Frame

48 weeks and EoT (96 weeks at maximum)

Secondary Outcome Measure Information:

Title

Secondary efficacy: The within-participant linear change from baseline to week 48 in quantitative EEG (global relative theta wave power), compared between active and placebo.

Description

Using a quantitative EEG the within-participant change from baseline to week 48 of the global relative theta wave power (4-8 Hz) will serve as a primary efficacy outcome.

Time Frame

48 weeks at minimum or until EoT (96 weeks at maximum)

Title

Secondary efficacy: The within-participant linear change with time in overall cognition as measured by the CogState Brief Battery (CBB) Z-score compared between active arm and placebo

Description

he within-participant linear change with time in overall cognition as measured by the CBB (CogState Detection, Identification, One Card Learning and One Back test) -Z-score

Time Frame

48 weeks and EoT (96 weeks at maximum)

Other Pre-specified Outcome Measures:

Title

Exploratory efficacy - The within-participants change from baseline in a set of representative functional network topology EEG measures compared between active arms and placebo.

Description

Evaluation of brain functional network activity and connectivity will be performed using quantitative EEG measurements, as described by (Briels et al. 2020; Poil et al. 2013; Scheltens et al. 2018) Global relative power in the delta (0.5 - 4 Hz), alpha (8 -13 Hz) and beta (13 - 30Hz) frequency bands Global posterior dominant peak frequency Amplitude Envelope Correlation (AEC) in the 4- 13 Hz band Functional network topology measures such as centrality, modularity, minimum spanning tree.

Time Frame

48 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Main Inclusion Criteria: Positive CSF AD biomarker signature according to the AA-NIA criteria Clinical syndrome of MCI or mild dementia according to the AA-NIA Research Framework A cognitive impairment in the WAIS IV Coding Test of at least 0.5 standard deviation below the normative data Adequate visual and auditory abilities to perform the cognitive and functional assessments in the opinion of the investigator Meeting the completion and performance criteria for the CogState NTB Outpatient with study partner capable of accompanying the subject on all applicable clinic visits Main Exclusion Criteria: Significant neurological or psychiatric disorders, other than AD, that may affect cognition. Atypical clinical presentations of MCI due to AD or mild dementia due to AD, such as the visual variant of AD (including posterior cortical atrophy), frontal variant or the language variant (including logopenic aphasia). Moderate and severe dementia with a Mini-Mental State Examination score (MMSE) below 20. Current presence of a clinically important major psychiatric disorder (e.g. major depressive disorder) as defined by DSM-5 criteria, or symptom(s) (e.g. hallucinations) that could affect the subject's ability to complete the study. History of clinically evident stroke. History of seizures within the last two years prior to the screening visit. Myocardial infarction within the last six months prior to screening. History of uncontrolled hypertension (in the opinion of the investigator) within six months prior to screening. Contraindication to lumbar puncture and MRI

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Everard Vijverberg, Dr

Organizational Affiliation

VUmc Alzheimer Centre

Official's Role

Study Chair

Facility Information:

Facility Name

Sanos Clinics

City

Ganderup

Country

Denmark

Facility Name

Sanos Clinics

City

Herlev

Country

Denmark

Facility Name

Sanos Clinics

City

Vejle

Country

Denmark

Facility Name

Charité - Universitätsmedizin Berlin

City

Berlin

ZIP/Postal Code

10450

Country

Germany

Facility Name

Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung

City

Magdeburg

ZIP/Postal Code

39120

Country

Germany

Facility Name

Institut für Studien zur Psychischen Gesundheit (ISPG)

City

Mannheim

ZIP/Postal Code

68165

Country

Germany

Facility Name

Klinikum rechts der Isar der TU München / Klinik für Psychiatrie und Psychotherapie

City

München

ZIP/Postal Code

81675

Country

Germany

Facility Name

Universitätsklinikum Münster / Klinik für Allgemeine Neurologie

City

Münster

ZIP/Postal Code

48149

Country

Germany

Facility Name

Klinik für Neurologie Universitätsklinikum Ulm

City

Ulm

ZIP/Postal Code

89081

Country

Germany

Facility Name

Brain Research Center

City

Amsterdam

Country

Netherlands

Facility Name

Brain Research Center

City

Den Bosch

Country

Netherlands

Facility Name

Brain Research Center Zwolle

City

Zwolle

ZIP/Postal Code

8025

Country

Netherlands

Facility Name

Podlaskie Centrum

City

Białystok

ZIP/Postal Code

15-756

Country

Poland

Facility Name

SOMED CR

City

Warsaw

ZIP/Postal Code

01-737

Country

Poland

Facility Name

SOMED CR

City

Łódź

ZIP/Postal Code

90-368

Country

Poland

Facility Name

Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych Uniwersytetu Medycznego w Łodzi

City

Łódź

ZIP/Postal Code

92-216

Country

Poland

Facility Name

Neurology (Memory Unit) - Hospital de la Santa Creu i Sant Pau

City

Barcelona

ZIP/Postal Code

08025

Country

Spain

Facility Name

Fundació ACE

City

Barcelona

ZIP/Postal Code

08028

Country

Spain

Facility Name

Cae Oroitu

City

Getxo

ZIP/Postal Code

48993

Country

Spain

Facility Name

Unidad de Neurociencias. Hospital Victoria Eugenia

City

Seville

ZIP/Postal Code

41009

Country

Spain

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

34425883

Citation

Vijverberg EGB, Axelsen TM, Bihlet AR, Henriksen K, Weber F, Fuchs K, Harrison JE, Kuhn-Wache K, Alexandersen P, Prins ND, Scheltens P. 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. Alzheimers Res Ther. 2021 Aug 23;13(1):142. doi: 10.1186/s13195-021-00882-9.

Results Reference

derived

Learn more about this trial

A Study to Evaluate Safety and Tolerability of Different Doses and Efficacy of PQ912 in Subjects With MCI and Mild AD

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