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

NCT ID: NCT04498650

Last Updated: 2024-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 259 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-06
• Study Completion Date: 2024-01-12

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.

Conditions

Early Alzheimers Disease; Mild Cognitive Impairment Due to AD

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablets to mimic PQ912 50 mg and 150 mg tablets

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

Group Type: EXPERIMENTAL

PQ912

Intervention Type: DRUG

PQ912 50 mg tablets and 150 mg tablets

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

Group Type: EXPERIMENTAL

PQ912

Intervention Type: DRUG

PQ912 50 mg tablets and 150 mg tablets

Interventions

PQ912

PQ912 50 mg tablets and 150 mg tablets

Intervention Type: DRUG

Placebo

Placebo tablets to mimic PQ912 50 mg and 150 mg tablets

Intervention Type: DRUG

Other Intervention Names

varoglutamstat

Eligibility Criteria

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

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nordic Bioscience A/S

INDUSTRY

Sponsor Role: collaborator

Amsterdam UMC, location VUmc

OTHER

Sponsor Role: collaborator

Vivoryon Therapeutics N.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Everard Vijverberg, Dr

Role: STUDY_CHAIR

VUmc Alzheimer Centre

Locations

Sanos Clinics

Ganderup, , Denmark

Sanos Clinics

Herlev, , Denmark

Sanos Clinics

Vejle, , Denmark

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Universitätsklinikum Schleswig-Holstein (UKSH), Klinik für Neurologie

Kiel, , Germany

Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung

Magdeburg, , Germany

Institut für Studien zur Psychischen Gesundheit (ISPG)

Mannheim, , Germany

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

München, , Germany

Universitätsklinikum Münster / Klinik für Allgemeine Neurologie

Münster, , Germany

Klinik für Neurologie Universitätsklinikum Ulm

Ulm, , Germany

Brain Research Center

's-Hertogenbosch, , Netherlands

Brain Research Center

Amsterdam, , Netherlands

Brain Research Center Zwolle

Zwolle, , Netherlands

Podlaskie Centrum

Bialystok, , Poland

SOMED CR

Lodz, , Poland

Klinika Psychiatrii Wieku Podeszłego i Zaburzeń Psychotycznych Uniwersytetu Medycznego w Łodzi

Lodz, , Poland

SOMED CR

Warsaw, , Poland

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

Barcelona, , Spain

Fundació ACE

Barcelona, , Spain

Cae Oroitu

Getxo, , Spain

Unidad de Neurociencias. Hospital Victoria Eugenia

Seville, , Spain

Countries

Denmark; Germany; Netherlands; Poland; Spain

References

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.

Reference Type: DERIVED

PMID: 34425883 (View on PubMed)

Other Identifiers

2019-003532-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PBD-01180

Identifier Type: -

Identifier Source: org_study_id