A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease
The purpose of this study is to test whether two investigational drugs called CAD106 and CNP520, administered separately, can slow down the onset and progression of clinical symptoms associated with Alzheimer's disease (AD) in participants at the risk to develop clinical symptoms based on their age and genotype.
- Alzheimer's Disease
- Eligible Ages
- Between 60 Years and 75 Years
- Eligible Genders
- Accepts Healthy Volunteers
- Consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype.
- Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential.
- Mini-Mental State Examination (MMSE) total score ≥ 24 (at screening or in previous 3 months) and cognitively unimpaired as evaluated by memory tests performed at screening.
- Homozygous APOE4 genotype.
- Participant's willingness to have a study partner.
- Any disability that may prevent the participants from completing all study requirements.
- Current medical or neurological condition that might impact cognition or performance on cognitive assessments.
- Advanced, severe progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the participant at special risk.
- History of malignancy of any organ system, treated or untreated, within the past 60 months.
- History of hypersensitivity to any of the investigational drugs or their excipients / adjuvant or to drugs of similar chemical classes.
- Indication for, or current treatment with ChEIs and/or another AD treatment (e.g. memantine).
- Contraindication or intolerance to MRI or PET investigations (with fluorinated radio ligands).
- Brain MRI results showing findings unrelated to AD that, in the opinion of the Investigator might be a leading cause to future cognitive decline, might pose a risk to the participant, or might prevent a satisfactory MRI assessment for safety monitoring.
- Suicidal Ideation in the past six months, or Suicidal Behavior in the past two years.
- A positive drug screen at Screening, if, in the Investigator's opinion, this is due to drug abuse.
- Significantly abnormal laboratory results at Screening, or infection not as a result of a temporary condition.
- Current clinically significant ECG findings. For Cohort - I only: Participants with previous organ transplantation or stem cell transplantation, or indication for treatment with anti-coagulants.
For Cohort - II only: Participants with depigmenting or hypopigmenting conditions (e.g. albinism vitiligo) or active / history of chronic urticarial in the past year.
- Phase 2/Phase 3
- Study Type
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
|CAD106 (450 µg) + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter||
|Placebo to CAD106 + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter||
|CNP520 (50 mg) capsules oral intake (p.o.)||
|Placebo to CNP520 capsules oral intake (p.o.)||
- Active, not recruiting
- Novartis Pharmaceuticals
This study will assess the effects of each of the two therapies given separately, both targeting amyloid, on cognition, global clinical status, and underlying pathology in participants at risk for the onset of clinical symptoms of Alzheimer's disease (AD). Cognitively unimpaired individuals with two APOE4 genes and age 60 to 75 years, inclusive, are selected as they represent a population at particularly high risk of progression to Mild Cognitive Impairment and/or dementia due to Alzheimer's disease.
The study follows a randomized, double-blind, placebo-controlled, two-cohort, parallel group design in which participants receive one of the investigational treatments or their matching placebo for at least 60 months up to a maximum of 96 months and no longer than when the target number of events for the TTE endpoint has been observed and confirmed in either cohort.
An unbalanced randomization (active: placebo) of 5:3 ratio in Cohort I (430 CAD106 :260 Placebo) and 3:2 ratio in Cohort II (390 CNP520 : 260 Placebo) will be applied. Randomization will be stratified by age group (60-64 years, 65-75 years) and region (North America/Other , Europe).
Participants who meet study entry requirements will be required to undergo at least one PET scan during the course of the study. Additional PET scans, blood and CSF collection will be voluntary. The study (also known as the Generation Study 1) is conducted as part of the Alzheimer's Prevention Initiative (API) program.