Safety, tolerability and efficacy of PQ912 in people with mild Alzheimer's disease.

Phase 1

• Conditions: Mild Cognitive Impairment and Mild Dementia due to Alzheimer’s Disease; MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2019-003532-23-DK
• Lead Sponsor: Vivoryon Therapeutics N.V.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-03-12
• Last Update Posted: 12 March 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 259

Inclusion Criteria

1. Signed and dated written informed consent obtained from the subject in accordance with local
regulations.
2. Male or female, aged = 50 to = 80 years.
3. A biomarker profile reflecting AD, according to the Alzheimer Association – National Institute on Aging (AA-NIA) Research Framework (Jack et al. 2018) defined as follows:
a) Screening CSF sample with an Aß42 concentration of <1000 pg/ml AND p-tau >19 pg/ml, or a ratio of p-tau/Aß42 of =0.024 as assessed by central laboratory, (Elecsys assay), OR, in case of subjects in whom CSF sampling is not feasible due to medical or technical reasons:
b) Existing Positive amyloid Positron-Emission Tomography (PET) evidence within six months of the screening visit.
4. Clinical syndrome of MCI or mild dementia according to the AA-NIA Research Framework (Jack et al. 2018)
5. A cognitive impairment in the WAIS-IV Coding Test of at least 0.5 standard deviations below the normative data (See Appendix 3). The cut-off score is inclusive, meaning that subjects scoring on or below the required score meet the criterion.
6. Meeting the completion and performance criteria for the CogState NTB.
7. Be in a stable therapeutic condition with respect to the current AD condition: either without specific current approved treatment (minimum wash-out period from a prior treatment is 10 weeks) and currently no plan to initiate currently approved treatment or being on an approved treatment for AD on a stable dose for at least 10 weeks.
8. Fluency in local language and evidence of adequate intellectual functioning in the opinion of the investigator.
9. Adequate visual and auditory abilities to perform the cognitive and functional assessments in the
opinion of the investigator.
10. Outpatient with study partner capable of accompanying the subject on all applicable clinic visits.
11. The subject and study partner are likely to be able to participate in all scheduled evaluations according to country and site practices.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 224

Exclusion Criteria

1. Significant neurological or psychiatric disorders, other than AD, that may affect cognition.
2. Atypical clinical presentations of MCI due to AD or mild dementia due to AD, such as visual variant of AD (including posterior cortical atrophy), frontal variant or language variant (including logopenic aphasia).
3. Moderate and severe dementia with Mini-Mental State Examination score (MMSE) below 20.
4. History of (maximally six months from screening) or screening visit brain MRI scan indicative of any other significant abnormality, including but not limited to severe white matter hyperintensities (Fazekas score 3), history or evidence of a single prior haemorrhage >1 cm3, multiple lacunar infarcts or evidence of single prior infarct >1 cm3, evidence of cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space-occupying lesions (e.g. brain tumours).
5. Current presence of 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 subject’s ability to complete study.
6. Current clinically important systemic illness likely to result in clinically relevant deterioration of subject’s condition or might affect subject’s safety during study.
7. History of clinically evident stroke.
8. History of seizures within last two years prior to screening visit.
9. Myocardial infarction within last six months prior to screening.
10. History of cancer within last two years prior to screening, with exception of any of following conditions: non-metastatic basal cell carcinoma, and squamous cell carcinoma of skin. Note: subjects can be included in study with prior history of cancer if evidence of no residual disease has been clinically confirmed within last six months before baseline.
11. History of uncontrolled hypertension (opinion of investigator) within six months prior to screening.
12. Other clinically important diseases or conditions or abnormalities of vital signs, physical examination, neurological examination, laboratory results, or electrocardiogram (ECG) examination (e.g. atrial fibrillation) that could compromise study or safety of subject.
13. Haemoglobin level less than 11 g/dL (6.8 mmol/L) at screening.
14. Clinically important infection within 30 days prior to screening e.g. chronic, persistent, or acute infection, such as bronchitis or urinary tract infection.
15. Known, untreated or insufficiently treated hypothyroidism, vitamin B12 or folate deficiency.
16. Any known hypersensitivity to investigational product PQ912 or any of excipients (section 7).
17. Severe hepatic failure (Child-Pugh C) or kidney failure (creatinine clearance (eGFR) = 30 mL/min/1.73m2) as estimated using MDRD method, or serum creatinine above 1.5-fold of Upper Limit of Normal (ULN) or Asparagine-Amino Transferase (AST) or Alanine-Amino Transferase (ALT) above 3 fold of ULN at screening.
18. Blood donation in 90 days prior to screening.
19. History of alcohol or drug dependence or abuse as defined by DSM-5 criteria within last two years prior to screening.
20. Claustrophobia or presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, CSF shunts, or metal fragments or foreign objects in eyes, skin, or body that would contraindicate a brain MRI scan.
21. Inadequate venous access to allow multiple blood draws.
22. Personnel involved in conduct of the study.
23. Previous participation in any investigation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified