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

• Register: EUCTR
• Last refreshed on: 1 February 2020
• Main ID: EUCTR2015-002715-15-FI
• Date of registration: 04/04/2016
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: To evaluate the efficacy of CAD106 and CNP520 in participants at risk for the onset of Alzheimer’s disease
• Scientific title: A randomized, double-blind, placebo-controlled, two-cohort parallel group study to evaluate the efficacy of CAD106 and CNP520 in participants at risk for the onset of clinical symptoms of Alzheimer’s disease
• Date of first enrolment: 18/07/2016
• Target sample size: 1340
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002715-15
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 4
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Belgium, Canada, Finland, Germany, Netherlands, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Medical Information Service
• Affiliation: Novartis Finland Oy

• Name: Medical Information Service
• Affiliation: Novartis Finland Oy

Key inclusion & exclusion criteria

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 (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, Treatment and Follow-up 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
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.
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.
Screening, Treatment and Follow-up Epochs 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
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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Alzheimer's disease
MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Code: CAD106
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: amilomotide
Current Sponsor code: CAD106
Other descriptive name: Q? VLP COUPLED VIA A CHEMICAL LINKER (SMPH) TO A?1-6 PEPTIDE
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 450-
Pharmaceutical form of the placebo: Powder for solution for injection
Route of administration of the placebo: Intramuscular use

Product Code: CNP520
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not established
Current Sponsor code: CNP520
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: - Baseline to Month 60.
- Baseline to Month 60.

Primary end point(s): - Time-to-event (MCI or dementia due to AD) measured by the MCI/dementia diagnostic verification form that includes measurements of cognitive function (RBANS, MMSE), function/cognition (CDR-SOB), daily function and subjective/observer memory concerns (ECog), plus Neuropsychiatric Inventory Questionnaire (NPI-Q), Geriatric Depression Scale, and safety MRI.
- API Preclinical Composite Cognitive (APCC) Battery derived from tests performed as part of the cognitive scales (MMSE, RBANS, and a subset of
Raven's Progressive Matrices) administered during the study.

Main Objective: - To demonstrate the effects of CAD106 and CNP520 vs. respective placebo on Time-to-event, with event defined as a diagnosis of MCI due to AD or dementia due to AD, whichever occurs first during the course of the study.
- To demonstrate the effects of CAD106 and CNP520 vs. respective placebo on cognition as measured by the change from Baseline to Month 60 in the APCC test score.

Secondary Objective: - To demonstrate the effects of CAD106/CNP520 vs respective placebo on global clinical status as measured by the change from Baseline to Month 60 in CDR-SOB score.
- To demonstrate the safety/tolerability of CAD106/CNP520 vs respective placebo as measured by AEs, changes in MRI, lab tests, vital signs, ECG, C-SSRS, injection-related reactions from Cohort I and skin-related AEs from Cohort II.
- To demonstrate the effects of CAD106/CNP520 vs respective placebo on cognition as measured by changes from Baseline to Month 60 on RBANS.
- To demonstrate the effects of CAD106/CNP520 vs respective placebo on function as measured by the change from Baseline to Month 60 in the ECog total scores reported by the participant and study partner, respectively.
- To demonstrate the effects of CAD106/CNP520 vs respective placebo on AD-related biomarkers as measured by change from Baseline to Months 24 and 60 in the subset of participants who consent.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Baseline to Month 60.

Secondary end point(s): - Global clinical status as measured by the change in Clinical Dementia Rating Scale Sum of Boxes score.

Secondary ID(s)

CAPI015A2201J

2015-002715-15-BE

Source(s) of Monetary Support

Novartis Pharma Services AG

Ethics review

Status: Approved
Approval date: 19/04/2016
Contact: