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: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

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

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-12-01
• Last Update Posted: 31 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• 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 POE genotype.
2. Male or female, age 60 to 75 years inclusive, at the time of signing Informed consent #1 (same age restriction also applied at informed consent #2).
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 7 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 18 or 19, the participant can only be included based on the investigator's judgment.
6. Participant 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; respectively 65-75 after reaching the maximum of 20% in the younger
age group 60-64).
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.
5. 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. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks before

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.
3. Advanced, severe progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the participant at special risk.
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, in-situ cervical cancer, localized vulvar carcinoma and localized prostrate carcinoma with no progression over the past two years 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 or PET investigations.
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 future 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 or dependence. Participants with a positive drug screen not believed to be related to drug abuse or dependence, can be re-screened once.
4. Significantly abnormal laboratory results at Screening as described in Appendix 13.4 or meeting the exclusionary alert values as specified in the Lab Manual. If, in the opinion of the Investigator, an abnormal
finding is the result of a temporary condition, the laboratory test can be repeated once.
5. Clinically significant active infection which has not resolved within 2 weeks prior to initial dosing.
6. Current clinically significant ECG findings.
7. Use of other investigational drugs prior to screening until:
- Blood concentration has returned to Baseline (or below Serological responder threshold) for biologics, e.g. antibodies induced by active immunotherapy; or
- Within 30 days or 5 half-lives, whichever is the longest for monoclonal antibodies or small molecules e.g. BACE-1 inhibitors.
8. Treatment in the four weeks prior to randomization with any drug or treatment known for their potential to cause major organ system toxicity, i.e. drugs that may require pe

Study & Design

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