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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02389413
Recruitment Status : Completed
First Posted : March 17, 2015
Last Update Posted : June 1, 2017
Sponsor:
Collaborators:
Julius Clinical, The Netherlands
VU University Medical Center
Information provided by (Responsible Party):
Vivoryon Therapeutics N.V.

Tracking Information
First Submitted Date  ICMJE March 5, 2015
First Posted Date  ICMJE March 17, 2015
Last Update Posted Date June 1, 2017
Study Start Date  ICMJE March 2015
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
Frequency of adverse events and serious adverse events (the study is a Phase II safety trial) [ Time Frame: 12 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 16, 2015)
  • 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
  • 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
  • Change from baseline in brain functional connectivity (measured by Magnetic Resonance Imaging (MRI) analysis) [ Time Frame: 12 weeks ]
  • Change from baseline in functional connectivity and network Analysis in electroencephalography (EEG) [ Time Frame: 12 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Tolerability of PQ912 in Subjects With Early Alzheimer's Disease
Official Title  ICMJE A Phase 2A Multicentre, Randomised, Double Blind, Placebo-Controlled, Parallel-Group Safety and Tolerability Study of PQ912 in Subjects With Early Alzheimer's Disease
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: PQ912 oral
  • Other: Placebo
Study Arms  ICMJE
  • Experimental: PQ912 oral
    PQ912 will be administered orally twice daily for 12 weeks.
    Intervention: Drug: PQ912 oral
  • Placebo Comparator: Placebo
    Placebo will be administered orally twice daily for 12 weeks.
    Intervention: Other: Placebo
Publications * Scheltens P, Hallikainen M, Grimmer T, Duning T, Gouw AA, Teunissen CE, Wink AM, Maruff P, Harrison J, van Baal CM, Bruins S, Lues I, Prins ND. Safety, tolerability and efficacy of the glutaminyl cyclase inhibitor PQ912 in Alzheimer's disease: results of a randomized, double-blind, placebo-controlled phase 2a study. Alzheimers Res Ther. 2018 Oct 12;10(1):107. doi: 10.1186/s13195-018-0431-6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 13, 2017)
120
Original Estimated Enrollment  ICMJE
 (submitted: March 16, 2015)
110
Actual Study Completion Date  ICMJE April 2017
Actual Primary Completion Date April 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Finland,   France,   Germany,   Netherlands,   Spain,   Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02389413
Other Study ID Numbers  ICMJE PBD01071
2014-001967-11 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Vivoryon Therapeutics N.V.
Study Sponsor  ICMJE Vivoryon Therapeutics N.V.
Collaborators  ICMJE
  • Julius Clinical, The Netherlands
  • VU University Medical Center
Investigators  ICMJE
Study Director: Frank Weber, Dr. Vivoryon Therapeutics N.V.
Study Chair: Philip Scheltens, Prof. Dr. VUmc Alzheimer Centre (p: +31 20 4440816)
PRS Account Vivoryon Therapeutics N.V.
Verification Date January 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP