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

Alzheimer's Disease Clinical Trial

— SAPHIR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02389413
• Other study ID #: PBD01071
• Secondary ID: 2014-001967-11
• Status: Completed
• Phase: Phase 2
• First received: March 5, 2015
• Last updated: May 31, 2017
• Start date: March 2015
• Est. completion date: April 2017

Study information

• Verified date: January 2017
• Source: Probiodrug AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 89 Years

Eligibility

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.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Drug:
• PQ912 oral

Other:
• Placebo

Locations

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

Sponsors (3)

Lead Sponsor	Collaborator
Probiodrug AG	Julius Clinical, VU University Medical Center

Countries where clinical trial is conducted

Belgium,  Finland,  France,  Germany,  Netherlands,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of adverse events and serious adverse events (the study is a Phase II safety trial)		12 weeks
Secondary	Exploratory clinical measures (measured by a questionnaire)	Mini-Mental State Examination (MMSE) Letter Fluency Test (LFT) Category Fluency Test (CFT) Geriatric Depression Scale (GDS) Cogstate Neuropsychological Test Battery	12 weeks
Secondary	Change from baseline of a panel of concept and AD-related biomarkers in Cerebrospinal fluid (CSF) (measured by Analysis of several biochemical assays)	QC activity, total-tau, phospho-tau, Abeta pattern, pro-inflammatory panel	12 weeks
Secondary	Change from baseline in brain functional connectivity (measured by Magnetic Resonance Imaging (MRI) analysis)		12 weeks
Secondary	Change from baseline in functional connectivity and network Analysis in electroencephalography (EEG)		12 weeks