Safety and Tolerability of PQ912 in Subjects With Early Alzheimer's Disease (SAPHIR)

May 31, 2017 updated by: Vivoryon Therapeutics N.V.

A Phase 2A Multicentre, Randomised, Double Blind, Placebo-Controlled, Parallel-Group Safety and Tolerability Study of PQ912 in Subjects With Early Alzheimer's Disease

The aim of this study is to evaluate the safety, tolerability and preliminary efficacy of PQ912 in subjects with Mild Cognitive Impairment (MCI) due to Alzheimers Disease (AD) or mild dementia due to AD.

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.

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.
120

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 Locations

  • Belgium
      • Hoboken, Belgium, 2660
        • Ziekenhuis Netwerk Antwerpen / Geheugenkliniek
  • Finland
      • Kuopio, Finland, 70211
        • Kliininen tutkimuskeskus
      • Oulu, Finland, 90220
        • Oulu University Hospital
      • Turku, Finland, 20520
        • CRST Oy
  • France
      • Bordeaux, France, 33076
        • CHU Bordeaux Pellegrin (CMRR)
      • Dijon, France, 21079
        • CHU François Mitterand (Centre Mémoire Ressources Recherche (CMRR))
      • Lille Cedex, France, 59037
        • CHRU de Lille / Hôpital Roger Salengro
      • Toulouse Cedex 9, France, 31059
        • Hôpital La Grave / Centre de Recherche Clinique
  • Germany
      • Berlin, Germany, 10450
        • Charité - Universitätsmedizin Berlin
      • Göttingen, Germany, 37075
        • Universitätsmedizin Göttingen / Klinik für Psychiatrie und Psychotherapie
      • Halle (Saale), Germany, 06112
        • Universitätsklinikum Halle (Saale) Klinik und Poliklinik für Psychiatrie, Psychotherapie und Psychosomatik
      • Leipzig, Germany, 04107
        • Arzneimittelforschung Leipzig GmbH
      • Magdeburg, Germany, 39120
        • Universitätsklinikum Magdeburg / Institut für Kognitive Neurologie und Demenzforschung
      • München, Germany, 81675
        • Klinikum rechts der Isar der TU München / Klinik für Psychiatrie und Psychotherapie
      • Münster, Germany, 48149
        • Universitätsklinikum Münster / Klinik für Allgemeine Neurologie
      • Rostock, Germany, 18147
        • Universitätsmedizin Rostock / Zentrum für Nervenheilkunde/ Klinik für Psychosomatik und Psychotherapeutische Medizin
      • Ulm, Germany, 89081
        • Neurologische Universitätsklinik Ulm
  • Netherlands
      • Amsterdam, Netherlands, 1081 GM
        • Alzheimer Research Center
  • Spain
      • Barcelona, Spain, 08025
        • Hospital de la Santa Creu i Sant Pau, Neurology Department, Memory Unit
      • Barcelona, Spain, 08028
        • Fundació ACE. Institut Català de Neurociències Aplicades
      • Santiago de Compostela, Spain, 15706
        • Complexo Hospitalario Universitario de Santiago (CHUS)
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena
  • Sweden
      • Mölndal, Sweden, 43141
        • Verksamheten för neuropsykiatri Sahlgrenska universitetssjukhuset

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 89 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Major Inclusion Criteria:

  • Signed and dated written informed consent
  • Male or surgically sterile or postmenopausal female aged ≥ 50 to ≤ 89 years. Male subjects with childbearing potential partners are willing to and should use condoms during treatment and until 28 days of the last dose of study medication.
  • Diagnosis of MCI due to AD or mild dementia due to AD with amnestic presentation, according to AA-NIA (Alzheimer's Association (AA) and the National Institute on (Aging NIA) criteria [Albert et al 2011; McKhann et al 2011]
  • Mini-Mental State Examination (MMSE) score of 21 to 30 inclusive at screening

  • A positive AD signature showing one of the following (either a, b, c, OR d):

    1. Screening CSF sample with an A-beta 42 concentration of less than 638 ng/L AND total tau >375 ng/L, as assessed by central laboratory.
    2. Screening CSF sample with an A-beta 42 concentration of less than 638 ng/L AND p-tau > 52 ng/L, as assessed by central laboratory.
    3. Tau/A-beta ratio > 0.52, as assessed by central laboratory.
    4. A positive amyloid PET if available prior to screening.
  • Treatment naïve, this means not having received any prior established specific treatment for MCI due to AD or mild dementia due to AD including no (prior) use of an acetylcholinesterase inhibitor or memantine. A maximum of two months of prior cumulative treatment with an acetylcholinesterase inhibitor or memantine is allowed if the acetylcholinesterase inhibitor or memantine was discontinued due to intolerance, and if this was done at least two months prior to baseline. Use of Souvenaid will be allowed if Souvenaid was discontinued at least twomonths prior to baseline, or if the subject is on stable dose for at least six months prior to baseline and is willing to continue during the study on the same dose and frequency.
  • Outpatient with study partner capable of accompanying the subject on all clinic visits. In accordance to Swedish regulations availability of study partner is not applicable for Sweden.

Major Exclusion Criteria:

  • Significant neurologic disease, 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) or the language variant (including logopenic aphasia).

  • Concomitant disorders:

    • Severe hepatic (Child-Pugh C) and/or kidney failure (creatinine clearance (estimated Glomerular Filtration Rate - eGFR) ≤ 30 ml/min/1.73m2) and/or serum creatinine above 1.5 fold of Upper Limit Normal (ULN) and/or Alanine-Amino Transferase (AST) or Asparagine-Amino Transferase (ALT) above 3 fold ULN at baseline.
    • History of or screening visit brain MRI scan indicative of any other significant abnormality.
    • 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.
    • . Current clinically important systemic illness that is likely to result in clinically relevant deterioration of the subject's condition or might affect the subject's safety during the study.
    • Other clinically important diseases or conditions or abnormalities of vital signs, physical examination, neurologic examination, laboratory results, or electrocardiogram (ECG) examination (e.g. atrial fibrillation) that could compromise the study or the safety of the subject.
    • Clinically important infection within 30 days prior to screening e.g. chronic persistent or acute infection, such as bronchitis or urinary tract infection.
    • Any known hypersensitivity to any of the excipients contained in the test article formulation.
    • Severe hepatic failure (Child-Pugh C) OR kidney failure (creatinine clearance (eGFR) ≤ 30 ml/min/1.73m2) OR serum creatinine above 1.5 fold of ULN OR AST or ALT above 3 fold of ULN at screening.´
  • Concomitant Medication/Therapies:

The following therapies are not permitted for the given intervals prior to baseline and until End-of-treatment (EOT):

  • Use of experimental medications for AD or any other investigational medications or devices for treatment of indications other than AD within 60 days prior to baseline.
  • Treatment with Souvenaid, except if the use of Souvenaid was discontinued at least two months prior to baseline, or if the subject is on stable dose for at least six months prior to baseline and is willing to continue the use of Souvenaid during the study on the same dose and frequency.
  • Concomitant treatment with St. John's Wort (a wash out phase of at least two weeks prior to baseline is required).
  • Any concomitant treatment which impairs cognitive function and cannot be washed out at least four weeks prior to baseline.

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: Quadruple

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.
Experimental: PQ912 oral
PQ912 will be administered orally twice daily for 12 weeks.
Drug: PQ912 oral
Placebo Comparator: Placebo
Placebo will be administered orally twice daily for 12 weeks.
Other: Placebo

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
Time Frame
Frequency of adverse events and serious adverse events (the study is a Phase II safety trial)
Time Frame: 12 weeks
12 weeks

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
Exploratory clinical measures (measured by a questionnaire)
Time Frame: 12 weeks
Mini-Mental State Examination (MMSE) Letter Fluency Test (LFT) Category Fluency Test (CFT) Geriatric Depression Scale (GDS) Cogstate Neuropsychological Test Battery
12 weeks
Change from baseline of a panel of concept and AD-related biomarkers in Cerebrospinal fluid (CSF) (measured by Analysis of several biochemical assays)
Time Frame: 12 weeks
QC activity, total-tau, phospho-tau, Abeta pattern, pro-inflammatory panel
12 weeks
Change from baseline in brain functional connectivity (measured by Magnetic Resonance Imaging (MRI) analysis)
Time Frame: 12 weeks
12 weeks
Change from baseline in functional connectivity and network Analysis in electroencephalography (EEG)
Time Frame: 12 weeks
12 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
Julius Clinical

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 Director: Frank Weber, Dr., Vivoryon Therapeutics N.V.
  • Study Chair: Philip Scheltens, Prof. Dr., VUmc Alzheimer Centre (p: +31 20 4440816)

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

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.
March 1, 2015

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.
April 1, 2017

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.
April 1, 2017

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).
March 5, 2015

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.
March 16, 2015

First Posted (Estimate)

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.
March 17, 2015

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.
June 1, 2017

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.
May 31, 2017

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.
January 1, 2017

More Information

Terms related to this study

Keywords

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.
  • PBD01071
  • 2014-001967-11 (EudraCT Number)

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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