To evaluate the efficacy of CAD106 and CNP520 in participants at risk for the onset of Alzheimer’s disease

Phase 1

• Conditions: Alzheimer's disease; MedDRA version: 19.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-002715-15-ES
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-10
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 1340

Inclusion Criteria

Pre-screening Epoch and Genetic Disclosure Follow-up inclusion criteria:
1. Written informed consent (Informed consent #1) obtained before any assessment is performed, including consent to receive disclosure of their APOE genotype.
2. Male or female, age 60 to 75 years inclusive, at the time of signing Informed consent #1.
a. Once the cap of approximately 20% of total participants in the age group 60-64 years is met, a restriction to this age group will apply.
3. Females must be considered post-menopausal and not of child bearing potential. Confirmation will be obtained for those who continue on to the Screening Epoch.
4. Mini-Mental State Examination (MMSE) total score =24.
5. Psychological readiness to receive APOE genotype information based on pre-disclosure rating scales:
a. Geriatric Depression Scale (GDS short form) total score <6.
If the score is between 6 and 10 (inclusive), the participant can only be included based on investigator’s judgment assessing in particular the scores of the questions:
i. Item 3: Do you feel your life is empty?”
ii. Item 6: Are you afraid that something bad is going to happen to you?”
iii. Item 12: Do you feel pretty worthless the way you are now?”
iv. Item 14: Do you feel your situation is hopeless?”
b. Six Item Subset Inventory of the STAI-AD total score <17.
If the score is between 17 and 19 (inclusive), the participant can only be included based on the investigator’s judgment.
6. Participant has evidence of adequate functioning (e.g. intellectual, visual and auditory) and is fluent in, and able to read the language in which the study assessments are administered (e.g. completion of at least 6 years of regular schooling or sustained employment).
7. Participant’s willingness to have a study partner for the Screening and Treatment Epoch.
Screening and Treatment Epoch inclusion criteria:
Participants eligible for inclusion must fulfill all of the following criteria prior to randomization:
1. Written informed consent (Informed consent #2) for participation to the Screening and Treatment Epochs (Participant must still be between 60-75 years, inclusive at the time of signing Informed consent #2).
2. Continue to meet all eligibility criteria from Pre-screening Epoch and Genetic Disclosure Follow-up, as confirmed by the review of the medical records by the Investigator.
3. Homozygous APOE4 genotype.
4. Cognitively unimpaired as defined by:
- At the screening visit, score of 85 or greater on the RBANS delayed memory index score AND CDR global score of 0.
With two exceptions:
- If the RBANS delayed memory index score is between 70 and 84 (inclusive) AND the global CDR score = 0, the participant may be allowed to continue ONLY if the Investigator judges that cognition is unimpaired following review of the MCI/dementia criteria.
- If the global CDR score = 0.5 AND the RBANS delayed memory index score is 85 or greater, the participant may be allowed to continue ONLY if the Investigator judges that cognition is unimpaired following review of the MCI/dementia criteria.

Exclusion Criteria

Pre-screening Epoch and Genetic Disclosure Follow-up exclusion criteria:
1. Any disability that may prevent the participants from completing all study requirements.
2. Current medical or neurological condition that might impact cognition or performance on cognitive assessments e.g., MCI, dementia, Huntington’s disease, Parkinson’s disease, Lyme disease, schizophrenia, bipolar disorder, major depression, active seizure disorder, history of multiple traumatic brain injuries, alcohol/drug abuse or dependence currently, or dependence within the last two years.
3. 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, uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure.
4. 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.
5. History of hypersensitivity to any of the investigational drugs or their excipients/adjuvant, or to drugs of similar chemical classes.
6. Indication for or current treatment with ChEIs and/or another AD treatment.
7. Contraindication or intolerance to MRI.
Screening and Treatment Epoch exclusion criteria:
Participants fulfilling any of the following criteria prior to randomization will be excluded.
Participants, who fulfill one or more exclusion criteria due to a temporary condition, or the use of treatment requiring a specific time window prior to randomization, can be re-screened at a later stage:
1. 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 cognitive decline, might pose a risk to the participant, or might confound MRI assessment for safety monitoring.
For Cohort I (CAD 106) only, in addition, evidence of ARIAH as demonstrated by:
- More than four cerebral microhemorrhages regardless of their anatomical location;
- Single area of superficial siderosis of the CNS or evidence of a prior cerebral macrohemorrhage.
2. Score yes” on item four or item five of the Suicidal Ideation Section of the C-SSRS if this ideation occurred in the past six 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 two years prior to screening.
3. A positive drug screen at Screening, 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 once.
4. 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 o

Study & Design

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