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

March 11, 2024 updated by: Vivoryon Therapeutics N.V.

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.

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
259

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Denmark
      • Ganderup, Denmark
        • Sanos Clinics
      • Herlev, Denmark
        • Sanos Clinics
      • Vejle, Denmark
        • Sanos Clinics
  • Germany
      • Berlin, Germany, 10450
        • Charité - Universitätsmedizin Berlin
      • Kiel, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie
      • Magdeburg, Germany, 39120
        • Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung
      • Mannheim, Germany, 68165
        • Institut für Studien zur Psychischen Gesundheit (ISPG)
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München / Klinik für Psychiatrie und Psychotherapie
      • Münster, Germany, 48149
        • Universitätsklinikum Münster / Klinik für Allgemeine Neurologie
      • Ulm, Germany, 89081
        • Klinik für Neurologie Universitätsklinikum Ulm
  • Netherlands
      • Amsterdam, Netherlands
        • Brain Research Center
      • Den Bosch, Netherlands
        • Brain Research Center
      • Zwolle, Netherlands, 8025
        • Brain Research Center Zwolle
  • Poland
      • Białystok, Poland, 15-756
        • Podlaskie Centrum
      • Warsaw, Poland, 01-737
        • SOMED CR
      • Łódź, Poland, 90-368
        • SOMED CR
      • Łódź, Poland, 92-216
        • Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych Uniwersytetu Medycznego w Łodzi
  • Spain
      • Barcelona, Spain, 08028
        • Fundació ACE
      • Barcelona, Spain, 08025
        • Neurology (Memory Unit) - Hospital de la Santa Creu i Sant Pau
      • Getxo, Spain, 48993
        • Cae Oroitu
      • Seville, Spain, 41009
        • Unidad de Neurociencias. Hospital Victoria Eugenia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Drug: Placebo
Placebo tablets to mimic PQ912 50 mg and 150 mg tablets
Experimental: 300 mg
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
Drug: PQ912
PQ912 50 mg tablets and 150 mg tablets
Other Names:
  • varoglutamstat
Experimental: 600 mg
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
Drug: PQ912
PQ912 50 mg tablets and 150 mg tablets
Other Names:
  • varoglutamstat

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary safety: The proportion of participants who experience any Adverse Event (AE), Serious Adverse Event (SAE), Adverse Event of Interest (AE-I)
Time Frame: 48 weeks
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
48 weeks
Primary efficacy: within-participant linear change with time of the combinded z-score for cognition compared between active arm and placebo.
Time Frame: 48 weeks and EoT (96 weeks at maximum)
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
48 weeks and EoT (96 weeks at maximum)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 48 weeks at minimum or until EoT (96 weeks at maximum)
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.
48 weeks at minimum or until EoT (96 weeks at maximum)
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
Time Frame: 48 weeks and EoT (96 weeks at maximum)
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
48 weeks and EoT (96 weeks at maximum)

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Exploratory efficacy - The within-participants change from baseline in a set of representative functional network topology EEG measures compared between active arms and placebo.
Time Frame: 48 weeks

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.
48 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Vivoryon Therapeutics N.V.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Amsterdam UMC, location VUmc
Nordic Bioscience A/S

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Everard Vijverberg, Dr, VUmc Alzheimer Centre

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 6, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 18, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 12, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 3, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 4, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 12, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PBD-01180
  • 2019-003532-23 (EudraCT Number)

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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