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

NCT04498650 | Completed Phase 2 DMC

• 2 other identifiers: PBD-011802019-003532-23
• Study Type: interventional
• Target: 259
• Locations: 5 countries
• Sites: 21

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.

Conditions

Early Alzheimers Disease; Mild Cognitive Impairment Due to AD

Outcome Measures

Primary Outcomes (2)

• 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

  48 weeks

• 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

  48 weeks and EoT (96 weeks at maximum)

Secondary Outcomes (2)

• 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.

  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

  48 weeks and EoT (96 weeks at maximum)

Other Outcomes (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.

  48 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

300 mg

EXPERIMENTAL

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

600 mg

EXPERIMENTAL

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

Interventions

PQ912 DRUG

PQ912 50 mg tablets and 150 mg tablets

Also known as: varoglutamstat

300 mg; 600 mg

Placebo DRUG

Placebo tablets to mimic PQ912 50 mg and 150 mg tablets

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vivoryon Therapeutics N.V.: lead
• Nordic Bioscience A/S: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (21)

Sanos Clinics

Ganderup, Denmark

Location

Sanos Clinics

Herlev, Denmark

Location

Sanos Clinics

Vejle, Denmark

Location

Charité - Universitätsmedizin Berlin

Berlin, 10450, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie

Kiel, 24105, Germany

Location

Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung

Magdeburg, 39120, Germany

Location

Institut für Studien zur Psychischen Gesundheit (ISPG)

Mannheim, 68165, Germany

Location

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

München, 81675, Germany

Location

Universitätsklinikum Münster / Klinik für Allgemeine Neurologie

Münster, 48149, Germany

Location

Klinik für Neurologie Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Brain Research Center

's-Hertogenbosch, Netherlands

Location

Brain Research Center

Amsterdam, Netherlands

Location

Brain Research Center Zwolle

Zwolle, 8025, Netherlands

Location

Podlaskie Centrum

Bialystok, 15-756, Poland

Location

SOMED CR

Lodz, 90-368, Poland

Location

Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych Uniwersytetu Medycznego w Łodzi

Lodz, 92-216, Poland

Location

SOMED CR

Warsaw, 01-737, Poland

Location

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

Barcelona, 08025, Spain

Location

Fundació ACE

Barcelona, 08028, Spain

Location

Cae Oroitu

Getxo, 48993, Spain

Location

Unidad de Neurociencias. Hospital Victoria Eugenia

Seville, 41009, Spain

Location

Related Publications (1)

• 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.

  PMID: 34425883 DERIVED

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Everard Vijverberg, Dr

  VUmc Alzheimer Centre

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: August 4, 2020
• Study Start: July 6, 2020
• Primary Completion: December 18, 2023
• Study Completion: January 12, 2024
• Last Updated: March 12, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

PL (4); DE (7); NL (3); ES (4); DK (3)