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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)

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ClinicalTrials.gov Identifier: NCT04498650
Recruitment Status : Recruiting
First Posted : August 4, 2020
Last Update Posted : August 10, 2022
Nordic Bioscience A/S
Amsterdam UMC, location VUmc
Information provided by (Responsible Party):
Vivoryon Therapeutics N.V.

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.

Condition or disease Intervention/treatment Phase
Early Alzheimers Disease Mild Cognitive Impairment Due to AD Drug: PQ912 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 6, 2020
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : July 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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 Name: 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 Name: varoglutamstat

Primary Outcome Measures :
  1. 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

  2. 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

Secondary Outcome Measures :
  1. 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.

  2. 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

Other Outcome Measures:
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04498650

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Contact: Katharina Fuchs +49 345 5559900 clinics@vivoryon.com
Contact: Kerstin Kuehn-Wache +49 345 5559900 clinics@vivoryon.com

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Sanos Clinics Recruiting
Ganderup, Denmark
Contact: Hanne Soerensen         
Principal Investigator: Pernille Luehdorf, MD         
Sanos Clinics Recruiting
Herlev, Denmark
Contact: Charlotta Arpi         
Principal Investigator: Ulla Schmidt, MD         
Sanos Clinics Recruiting
Vejle, Denmark
Contact: Ellen Frank         
Principal Investigator: Peter Alexandersen, MD         
Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 10450
Contact: Katja Lindner         
Principal Investigator: Oliver Peters, MD         
Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie Recruiting
Kiel, Germany, 24105
Contact: Katrin Lange         
Principal Investigator: Thorsten Bartsch, MD         
Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung Recruiting
Magdeburg, Germany, 39120
Contact: Urte Schneider         
Principal Investigator: Emrah Duezel, MD         
Institut für Studien zur Psychischen Gesundheit (ISPG) Recruiting
Mannheim, Germany, 68165
Contact: Dörthe Hafke         
Principal Investigator: Georg Adler, MD         
Klinikum rechts der Isar der TU München / Klinik für Psychiatrie und Psychotherapie Recruiting
München, Germany, 81675
Contact: Karin Liebl         
Principal Investigator: Timo Grimmer, MD         
Universitätsklinikum Münster / Klinik für Allgemeine Neurologie Recruiting
Münster, Germany, 48149
Contact: Gloria Lwanga         
Principal Investigator: Matthias Pawlowski, MD         
Klinik für Neurologie Universitätsklinikum Ulm Recruiting
Ulm, Germany, 89081
Principal Investigator: Doerte Polivka, MD         
Brain Research Center Recruiting
Amsterdam, Netherlands
Contact: Femke van der Linden         
Principal Investigator: Sterre Rutgers, MD         
Brain Research Center Recruiting
Den Bosch, Netherlands
Contact: Hetty Den Burger         
Principal Investigator: Paul Dautzenberg, MD         
Brain Research Center Zwolle Recruiting
Zwolle, Netherlands, 8025
Contact: Carlie Dille-Amo         
Principal Investigator: Niels Prins, MD         
Neurology (Memory Unit) - Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08025
Contact: Andrea Subirana         
Principal Investigator: Alberto Lleo, MD         
Fundació ACE Recruiting
Barcelona, Spain, 08028
Contact: Mar Buendia         
Principal Investigator: Merce Boada, MD         
Unidad de Neurociencias. Hospital Victoria Eugenia Recruiting
Seville, Spain, 41009
Contact: Angelles Barro         
Principal Investigator: Felix Vinuela, MD         
Sponsors and Collaborators
Vivoryon Therapeutics N.V.
Nordic Bioscience A/S
Amsterdam UMC, location VUmc
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Study Chair: Philip Scheltens Amsterdam UMC, location VUmc
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Vivoryon Therapeutics N.V.
ClinicalTrials.gov Identifier: NCT04498650    
Other Study ID Numbers: PBD-01180
2019-003532-23 ( EudraCT Number )
First Posted: August 4, 2020    Key Record Dates
Last Update Posted: August 10, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Cognitive Dysfunction