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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT02565511
Ethics application status
Date submitted
28/09/2015
Date registered
1/10/2015

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
GS1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimers 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
Treatment: Other - CAD106 Immunotherapy
Other interventions - Placebo to CAD106
Treatment: Drugs - CNP520
Other interventions - Placebo to CNP520
Other interventions - Alum

Experimental: Cohort I (CAD106) - CAD106 (450 µg) + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Placebo comparator: Cohort I (CAD106 Placebo) - Placebo to CAD106 + Alum (450 µg) intra-muscular injection at Weeks 1, 7, 13 and every 13 weeks thereafter

Experimental: Cohort II (CNP520) - CNP520 (50 mg) capsules taken orally once daily

Placebo comparator: Cohort II (CNP520 Placebo) - Matching Placebo to CNP520 capsules taken orally once daily


Treatment: Other: 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

Other interventions: Alum
Alum was mixed with reconstituted CAD106 as adjuvant therapy to maximize the effectiveness of CAD106
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time to Event (Diagnosis of Mild Cognitive Impairment or Dementia, Due to Alzheimer's Disease (AD))
Timepoint [1] 0 0
Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Primary outcome [2] 0 0
Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
Timepoint [2] 0 0
CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [1] 0 0
Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) Score
Timepoint [1] 0 0
CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [2] 0 0
Change in the Total Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Timepoint [2] 0 0
CI = Baseline to Weeks 26, 52,78 104 and Baseline to last assessment; CII = Baseline to Weeks 26, 52, 78, 104 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [3] 0 0
Change in the Index Scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
Timepoint [3] 0 0
CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [4] 0 0
Change in the Everyday Cognition Scale (ECog-Subject) Total Scores
Timepoint [4] 0 0
CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [5] 0 0
Change in the Everyday Cognition Scale (ECog-Informant) Total Scores
Timepoint [5] 0 0
CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [6] 0 0
Number of Participants With Newly Occurring Safety MRI Abnormalities (ARIA-E, ARIA-H,White Matter Disease and Any Other MRI Abnormalities)
Timepoint [6] 0 0
Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Secondary outcome [7] 0 0
Annualized Percent Change on Volume of Brain Regions
Timepoint [7] 0 0
CI = Baseline to Weeks 26, 52 and Baseline to last assessment; CII = Baseline to Weeks 26, 52 and Baseline to Last on-treatment and Baseline to Last off-treatment
Secondary outcome [8] 0 0
Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 40 (Aß40)
Timepoint [8] 0 0
Baseline to last assessment
Secondary outcome [9] 0 0
Change in Cerebrospinal Fluid (CSF) Levels of Amyloid Beta 42 (Aß42)
Timepoint [9] 0 0
Baseline to last assessment
Secondary outcome [10] 0 0
Change in Cerebrospinal Fluid (CSF) Levels of Total Tau and Phosphorylated Tau
Timepoint [10] 0 0
Baseline to last assessment
Secondary outcome [11] 0 0
Change in Neurofibrillary Tangle Burden as Measured by Standardized Uptake Ratio (SUVR) of PET Scans With Tau Radiotracer (Where Available)
Timepoint [11] 0 0
Baseline to last assessment
Secondary outcome [12] 0 0
Cohort I : Annualized Change in Amyloid Deposition as Measured by Centiloids of Positron Emission Tomography (PET) Scan With Amyloid Radiotracer
Timepoint [12] 0 0
Baseline up to approximately Week 104
Secondary outcome [13] 0 0
Change in Serum Neurofilaments
Timepoint [13] 0 0
Baseline to Week 26 and week 52, CI baseline to last assessment. CII baseline to last on-treatment and to last off-treatment
Secondary outcome [14] 0 0
Number of Suicidal Ideation or Behavior Events
Timepoint [14] 0 0
Baseline to end of exposure for a maximum of 1455 days for CI and 907 days for CII
Secondary outcome [15] 0 0
Cohort I : Change in Cognition as Measured by APCC and CDR-SOB Scores and Antibody Response
Timepoint [15] 0 0
Month 6 to Month 60
Secondary outcome [16] 0 0
Cohort I: Peak Concentration (Cmax) of CAD106 Induced Abeta-specific Antibody Titers
Timepoint [16] 0 0
Week 9, 13, 15, 26 and quarterly thereafter (trough values)
Secondary outcome [17] 0 0
Cohort I: Area Under the Concentration Curve (AUC) of CAD106 Induced Abeta-specific Antibody Titers
Timepoint [17] 0 0
Week 9, 13, 15, 26 and quarterly thereafter (trough values)

Eligibility
Key inclusion criteria
Key

* Consented 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 were to be post-menopausal.
* Mini-Mental State Examination (MMSE) total score = 24 and cognitively unimpaired as evaluated by memory tests
* Homozygous APOE4 genotype.
* Participant willing to have a study partner.

Key
Minimum age
60 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Any disability that prevented the participant from completing all study requirements.
* Current medical or neurological condition that could have impacted cognition or performance on cognitive assessments.
* Advanced, severe progressive or unstable disease that may have interfered 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 60 months prior to screening.
* History of hypersensitivity to any of the investigational drugs or their excipients / adjuvant or to drugs of similar chemical classes.
* Indication or on 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 could have been a leading cause to future cognitive decline, pose a risk to the participant, or prevent a satisfactory MRI assessment for safety monitoring.
* Suicidal Ideation in the past six months or Suicidal Behavior in the past two years, prior to screening.
* A positive drug screen at Screening, if, in the Investigator's opinion, this was 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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/11/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/04/2020
Sample size
Target
Accrual to date
Final
480
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
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Colorado
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Connecticut
Country [5] 0 0
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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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Kansas
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Kentucky
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Maine
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Massachusetts
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Michigan
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Minnesota
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Missouri
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Nebraska
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Nevada
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New Jersey
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New York
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Tennessee
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Vermont
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Wisconsin
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Belgium
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Gent
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Nova Scotia
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Finland
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Turku
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Bayreuth
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Germany
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Berlin
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Boblingen
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Germany
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Gottingen
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Halle
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Kiel
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Koeln
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Leipzig
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Mannheim
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Germany
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Münster
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Germany
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Siegen
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Germany
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Wenzenbach
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Netherlands
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Amsterdam
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Spain
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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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United Kingdom
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Bristol
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Devon
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Surrey
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Avon
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Birmingham
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Dundee
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Glasgow
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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
Commercial sector/industry
Name [3] 0 0
Amgen
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02565511