A randomized, double-blind, placebo-controlled, parallel group study to evaluate the efficacy and safety of CNP520 in participants at risk for the onset of clinical symptoms of Alzheimer*s Disease (AD)

Phase 3

Completed

Conditions: 10042258
Alzheimer's Disease
Dementia

Registration Number: NL-OMON50603

Lead Sponsor: ovartis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 30

Inclusion Criteria

Screening part I: Participants eligible for inclusion must fulfill all of the
following criteria prior to scheduling the genetic disclosure.
- Written informed consent must be obtained before any assessment is performed
as part of the study, including consent to receive disclosure of their risk
estimates to develop clinical symptoms of AD based on their APOE genotype and,
if HTs, with evidence of elevated brain amyloid.
- Male or female, age 60-75 years inclusive, at the time of signing the
informed consent.
- Females must be considered post-menopausal and not of child bearing potential
i.e. they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g. history of vasomotor symptoms), or have had
surgical bilateral oophorectomy (with or without hysterectomy), total
hysterectomy, or tubal ligation.
- Intellectually, visually and auditorily capable, fluent in, and able to read,
the language in which study assessments are administered (e.g. completion of at
least 6 years of regular schooling or sustained employment or equivalent local
level of knowledge).
- Mini-Mental State Examination total score *24.
- Willing to have a study partner throughout the study.Screening part II:
Participants eligible for inclusion must fulfill all of the following criteria
prior to randomization based on the results from the screening test procedures.
- Carrier of at least one *4 allele of the APOE gene: HMs with elevated or not
elevated brain amyloid OR HTs with elevated brain amyloid (as measured in CSF
collected via lumbar puncture or by amyloid PET imaging).
Note: In cases where both lumbar puncture (CSF) amyloid and amyloid PET imaging
tests are performed, at least one should be indicative of elevated brain
amyloid.
- Cognitively unimpaired at screening visit as defined by: Score of 85 or
greater on the RBANS delayed memory index score AND CDR global score of 0
- Having a study partner who agrees to participate in the study and who is
intellectually, visually, and auditorily capable, and fluent in, and able to
read, the language in which study assessments are administered.

Exclusion Criteria

Screening part I: Participants will be excluded if they fulfill any of the
following criteria prior to scheduling the genetic disclosure.
- Current medical or neurological condition that might impact cognition or
performance on cognitive assessments e.g. MCI, dementia, Huntington*s or
Parkinson*s disease etc.
- Advanced, severe progressive or unstable disease that may interfere with the
safety, tolerability and study assessments, or put the participant at special
risk e.g. active hepatitis, HIV infection, severe renal impairment, severe
hepatic impairment etc.
- History of malignancy of any organ system, treated or untreated, within the
past 60 months, regardless of whether there is evidence of local recurrence or
metastases. However, localized nonmalignant tumors not requiring systemic
chemo- or radio-therapy, localized basal or squamous cell carcinoma of the
skin, or in-situ cervical cancer are permitted.
- Current treatment with Cholinesterase Inhibitors and/or another AD treatment.
- Clinically relevant depigmenting or hypopigmenting conditions or
active/history of chronic urticaria in the past year.
- Score *yes* on item 4 or 5 of the Suicidal Ideation section of the C-SSRS
PRO, if this ideation occurred in the past 6 months, or *yes* on any item of
the Suicidal Behavior section, except for the *Non-Suicidal Self-Injurious
Behavior*, if this behavior occurred in the past 2 years prior to screening.
- Lacking psychological readiness to receive APOE genotype/amyloid status
results, as assessed based on investigator*s judgement supported by the
pre-disclosure rating scales: Geriatric Depression Scale total score >6; Six
Item Subset Inventory of the modified State Trait Anxiety Inventory total score
>17.
- Contraindication or intolerance to MRI investigations.Screening part II:
Participants fulfilling any of the following criteria based on results from the
screening test procedures will be excluded.
- A positive drug screen, if, in the investigator*s opinion, this is due to
drug abuse. Participants with a positive drug screen not believed to be related
to drug abuse can be re-screened.
- Significantly abnormal laboratory results at screening, meeting the
exclusionary alert values specified in the Laboratory Manual. If, in the
opinion of the investigator, an abnormal finding is the result of a temporary
condition, the laboratory test can be repeated.
- Current significant ECG findings from central reader that are assessed as
clinically significant by the investigator. QTc interval >500 ms is
exclusionary.
- Brain MRI results from the central reading showing findings unrelated to AD
that, in the opinion of the investigator might be a leading cause of future
cognitive decline, might pose a risk to the participant, or might confound MRI
assessment for safety monitoring (e.g. extensive white matter lesions, stroke,
cerebrovascular disease as evidenced by multiple lacunar infarcts *20 mm or
single infarct >20 mm, evidence of cerebral contusion etc.).
- If PET scans are scheduled for this participant: Total dosimetry above the
acceptable exposure in the country when combining the previous or planned
Nuclear Medicine Radiology exposure and the scheduled study PET scan(s).
- If CSF sampling is scheduled for this participant: Contraindication to lumbar
punctur