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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02565511




Registration number
NCT02565511
Ethics application status
Date submitted
28/09/2015
Date registered
1/10/2015
Date last updated
17/07/2019

Titles & IDs
Public title
A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms 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.
Secondary ID [1] 0 0
2015-002715-15
Secondary ID [2] 0 0
CAPI015A2201J
Universal Trial Number (UTN)
Trial acronym
Generation S1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - CAD106 Immunotherapy
Other interventions - Placebo to CAD106
Treatment: Drugs - CNP520
Other interventions - Placebo to CNP520

Experimental: Arm#1 - CAD106 (450 µg) + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter

Placebo Comparator: Arm#2 - Placebo to CAD106 + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter

Experimental: Arm#3 - CNP520 (50 mg) capsules oral intake (p.o.)

Placebo Comparator: Arm#4 - Placebo to CNP520 capsules oral intake (p.o.)


Other interventions: CAD106 Immunotherapy
Participants will be given i.m. injections at Weeks 1, 7, 13 and quarterly i.m. injections (every 13 weeks) thereafter, until the last injection 3 month prior to completion of the Treatment Epoch.

Other interventions: Placebo to CAD106
Participants will be given i.m. injections at Weeks 1, 7, 13 and quarterly i.m. injections (every 13 weeks) thereafter, until the last injection 3 month prior to completion of the Treatment Epoch.

Treatment: Drugs: CNP520
CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch.

Other interventions: Placebo to CNP520
Placebo to CNP520 p.o. for the duration of the Treatment Epoch

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to diagnosis of MCI due to Alzheimer's Disease (AD) or dementia due to Alzheimer's Disease - Time when diagnosis is confirmed by adjudication committee
Timepoint [1] 0 0
Through study completion, an average of 5 years
Primary outcome [2] 0 0
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score - Composite score derived from the specific tests from the Repeatable Battery for the Assessment of Neurological Status (RBANS), Mini-Mental State Examination (MMSE), Raven's Progressive Matrices
Timepoint [2] 0 0
Baseline to Month 60
Secondary outcome [1] 0 0
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score - To assess the effects of CAD106 and CNP520, vs. respective placebo on global clinical status as measured by the change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score.
Timepoint [1] 0 0
Baseline to Month 60
Secondary outcome [2] 0 0
Number of participants with Adverse Events as a measure of Safety and Tolerability - To assess the safety and tolerability of CAD106 and CNP520, vs. respective placebo by measured adverse events (AEs), and changes in the brain structural MRI, laboratory tests, non-cognitive neurological and psychiatric examinations including the self-reported Columbia Suicide Severity Rating Scale (eC-SSRS), vital signs and electrocardiogram (ECG).
Cohort - I: Injection-related reactions will also be analyzed. Cohort - II: Skin related AEs by regular skin examinations and centralized dermatological monitoring.
Timepoint [2] 0 0
Through study completion, an average of 5 years
Secondary outcome [3] 0 0
Change on the Total Scale score and individual neurocognitive domain index scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) - To assess the effects of CAD106 and CNP520, vs. respective placebo on cognition as measured by changes on the Total Scale score and individual neurocognitive domain index scores of the RBANS.
Timepoint [3] 0 0
Baseline to Month 60
Secondary outcome [4] 0 0
Change in the Everyday Cognition scale (ECog) total scores - To assess the effects of CAD106 and CNP520, vs. respective placebo on function as measured by the change in ECog total score reported by the participant and study partner, respectively.
Timepoint [4] 0 0
Baseline to Month 60
Secondary outcome [5] 0 0
Change in Alzheimer's Disease related biomarkers - To assess the effects of CAD106 and CNP520, vs. respective placebo on AD-related biomarkers (amyloid deposition and measures of neurodegeneration) as measured by changes on:
amyloid tracer and tau tracer obtained using brain positron emission tomography (PET) imaging, volumetric MRI measurements, and CSF/blood Aß40, Aß42, total tau and phosphorylated tau181 and NFL levels.
Timepoint [5] 0 0
Baseline to Months 24 and 60
Secondary outcome [6] 0 0
Change in APCC Test Score - To assess the effects of antibody response to CAD106 vs. placebo on cognition as measured by changes on the APCC test score
Timepoint [6] 0 0
Month 6 to Month 60
Secondary outcome [7] 0 0
Change in CDR-SOB - To assess the effects of antibody response to CAD106 vs. placebo on cognition as measured by changes on the CDR-SOB.
Timepoint [7] 0 0
Month 6 to Month 60
Secondary outcome [8] 0 0
Aß-specific immune response - To describe serological immune response to CAD106 injections as measured by Aß-specific antibody titers generated
Timepoint [8] 0 0
Through study completion, an average of 5 years

Eligibility
Key inclusion criteria
Key

- 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.

Key
Minimum age
60 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2/Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Darlinghurst
Recruitment hospital [2] 0 0
Novartis Investigative Site - Heidelberg Heights
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3081 - Heidelberg Heights
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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California
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Colorado
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Connecticut
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District of Columbia
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Florida
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Georgia
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Idaho
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Illinois
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Indiana
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Maine
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Michigan
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Nebraska
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Nevada
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New York
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Halle
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Koeln
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Mannheim
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Münster
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Nuernberg
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Siegen
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Ulm
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Wenzenbach
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Netherlands
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Amsterdam
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Barcelona
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Spain
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Madrid
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Spain
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Donostia-San Sebastian
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Switzerland
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CH
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Switzerland
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Lausanne
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Bristol
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London
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Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Banner Alzheimer's Institute
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Institute on Aging (NIA)
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Alzheimer's Association
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Commercial sector/Industry
Name [4] 0 0
Amgen
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02565511
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications