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History of Changes for Study: NCT02565511
A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation)
Latest version (submitted July 7, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 September 29, 2015 None (earliest Version on record)
2 December 22, 2015 Recruitment Status, Contacts/Locations, Arms and Interventions, Study Status, Outcome Measures and Sponsor/Collaborators
3 June 29, 2016 Study Status, Contacts/Locations, Study Design and Oversight
4 August 1, 2016 Contacts/Locations and Study Status
5 November 10, 2016 Outcome Measures, Arms and Interventions, Study Status, Contacts/Locations, Eligibility and Study Description
6 April 14, 2017 Study Status and Contacts/Locations
7 June 15, 2017 Contacts/Locations, Study Status, Oversight, Study Design and Study Identification
8 June 19, 2017 Contacts/Locations, Study Status and IPDSharing
9 July 7, 2017 Study Status and Contacts/Locations
10 July 14, 2017 Contacts/Locations and Study Status
11 July 31, 2017 Contacts/Locations and Study Status
12 September 6, 2017 Study Status and Contacts/Locations
13 September 27, 2017 Contacts/Locations and Study Status
14 October 17, 2017 Study Status and Contacts/Locations
15 November 1, 2017 Contacts/Locations and Study Status
16 December 1, 2017 Study Status and Contacts/Locations
17 January 12, 2018 Study Status and Contacts/Locations
18 February 2, 2018 Study Status and Contacts/Locations
19 March 19, 2018 Contacts/Locations, Study Status, Outcome Measures, IPDSharing, Eligibility, Study Description and Study Identification
20 March 28, 2018 Contacts/Locations, Study Status and References
21 April 17, 2018 Contacts/Locations and Study Status
22 May 4, 2018 Contacts/Locations and Study Status
23 June 6, 2018 Contacts/Locations and Study Status
24 July 17, 2018 Study Status and Contacts/Locations
25 July 31, 2018 Eligibility and Study Status
26 August 3, 2018 Contacts/Locations and Study Status
27 August 16, 2018 Contacts/Locations and Study Status
28 September 7, 2018 Contacts/Locations and Study Status
29 September 25, 2018 Contacts/Locations and Study Status
30 October 4, 2018 Study Status, Contacts/Locations and Study Design
31 October 10, 2018 Contacts/Locations, Study Design and Study Status
32 October 16, 2018 Contacts/Locations, Study Design and Study Status
33 October 30, 2018 Contacts/Locations and Study Status
34 November 21, 2018 Contacts/Locations, Study Status and Study Design
35 December 7, 2018 Study Status, Contacts/Locations and Study Design
36 December 14, 2018 Contacts/Locations, Study Design and Study Status
37 January 8, 2019 Contacts/Locations and Study Status
38 January 16, 2019 Contacts/Locations and Study Status
39 March 24, 2019 Contacts/Locations, Study Status, Outcome Measures and Study Description
40 March 27, 2019 Contacts/Locations and Study Status
41 April 12, 2019 Contacts/Locations and Study Status
42 April 30, 2019 Contacts/Locations and Study Status
43 July 16, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
44 September 5, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
45 October 2, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
46 October 25, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
47 February 15, 2020 Recruitment Status, Contacts/Locations, Study Status and Study Design
48 June 16, 2020 Recruitment Status and Study Status
49 July 19, 2020 Contacts/Locations and Study Status
50 July 27, 2020 Contacts/Locations and Study Status
51 February 17, 2021 Study Status
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Results Submission Events
52 July 7, 2021 Contacts/Locations, Outcome Measures, Study Status, Arms and Interventions, Eligibility, Conditions, Study Description, Document Section, Results, Sponsor/Collaborators and Study Identification
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Study NCT02565511
Submitted Date:  September 29, 2015 (v1)

Open or close this module Study Identification
Unique Protocol ID: CAPI015A2201J
Brief Title: A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation)
Official 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 IDs: 2015-002715-15 [EudraCT Number]
Open or close this module Study Status
Record Verification: September 2015
Overall Status: Not yet recruiting
Study Start: November 2015
Primary Completion: August 2023 [Anticipated]
Study Completion: August 2023 [Anticipated]
First Submitted: September 28, 2015
First Submitted that
Met QC Criteria:
September 29, 2015
First Posted: October 1, 2015 [Estimate]
Last Update Submitted that
Met QC Criteria:
September 29, 2015
Last Update Posted: October 1, 2015 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators: Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:

This study will assess the effects of each of the two therapies given separately, both targeting amyloid, on cognition, global clinical status, and underlying pathology in participants at risk for the onset of clinical symptoms of Alzheimer's disease (AD). Cognitively unimpaired individuals with two APOE4 genes and age 60 to 75 years, inclusive, are selected as they represent a population at particularly high risk of progression to MCI and/or dementia due to Alzheimer's disease.

The study follows a randomized, double-blind, placebo-controlled, two-cohort, parallel group design in which participants receive one of the investigational treatments or their matching placebo for at least 60 months.

An unbalanced randomization (active: placebo) of 5:3 ratio in Cohort I (430 CAD106 :260 Placebo) and 3:2 ratio in Cohort II (390 CNP520 : 260 Placebo) will be applied.

Participants who meet study entry requirements will be required to undergo at least two PET scans during the course of the study. Additional PET scans, blood and CSF collection will be voluntary. The study (also known as the API APOE4 trial) is conducted as part of the Alzheimer's Prevention Initiative (API) program.

Open or close this module Conditions
Conditions: Alzheimer's Disease
Keywords: Randomization, Placebo controlled, Parallel-group, APOE4 Homozygotes, Preclinical Alzheimer's Disease (AD), Aβ lowering
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2/Phase 3
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 1340 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm#1
CAD106 + Alum given i.m. at week 1, 7, 13 , 24 and quarterly thereafter
Biological: 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.
Placebo Comparator: Arm#2
Matching placebo to CAD106 + Alum given i.m. at week 1, 7, 13, 24 and quarterly thereafter
CAD106 Matching Placebo
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.
Experimental: Arm#3
CNP520 capsules for once daily oral intake (p.o.)
Drug: CNP520
CNP520 capsule for once daily oral (p.o) administration at the dose determined prior to initiation of Cohort II. Not yet active.
Placebo Comparator: Arm#4
Matching placebo to CNP520 capsules for once daily oral intake (p.o.)
CNP520 Matching Placebo
CNP520 capsule for once daily oral (p.o) administration at the dose determined prior to initiation of Cohort II. Not yet active.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Time to diagnosis of MCI or dementia due to Alzheimer's Disease
[ Time Frame: Through study completion, an average of 5 years ]

Time when diagnosis is confirmed by adjudication committee
2. Change in the Alzheimer's Prevention Initiative Composite Cognitive (APCC) Test Score
[ Time Frame: Baseline to Month 60 ]

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
Secondary Outcome Measures:
1. Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score
[ Time Frame: Baseline to Month 60 ]

To assess the effects of CAD106 and CNP520, respectively, vs. placebo on global clinical status as measured by the change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score.
2. Number of participants with Adverse Events as a measure of Safety and Tolerability
[ Time Frame: Through study completion, an average of 5 years ]

To assess the safety and tolerability of CAD106 and CNP520, respectively, vs. placebo by measured adverse events (AEs), and changes in the brain MRI, laboratory tests, vital signs, electrocardioagram (ECG), and Columbia Suicide Severity Rating Scale (C-SSRS). Injection-related reactions will also be collected for participants from Cohort I.
3. Change on the Total Scale score and individual neurocognitive domain index scores of the RBANS
[ Time Frame: Baseline to Month 60 ]

To assess the effects of CAD106 and CNP520, respectively, vs. placebo on cognition as measured by changes on the Total Scale score and individual neurocognitive domain index scores of the RBANS.
4. Change in the Everyday Cognition scale (ECog) total scores
[ Time Frame: Baseline to Month 60 ]

To assess the effects of CAD106 and CNP520, respectively, vs. placebo on function as measured by the change on ECog total score reported by the participant and study partner.
5. Change in Alzheimer's Disease related biomarkers
[ Time Frame: Baseline to Months 24 and 60 ]

To assess the effects of CAD106 and CNP520, respectively, vs. placebo on AD-related biomarkers (amyloid deposition and measures of neurodegeneration) as measured by changes on:

amyloid tracer 18F-florbetapir and tau tracer 18F-AV-1451 obtained using brain positron emission tomography (PET) imaging, volumetric MRI measurements, and CSF Aβ, total tau and phosphorylated tau levels.

6. Change in APCC Test Score
[ Time Frame: Month 6 to Month 60 ]

To assess the effects of antibody response to CAD106 vs. placebo on cognition as measured by changes on the APCC test score and CDR-SOB.
7. Aβ-specific immune response
[ Time Frame: Through study completion, an average of 5 years ]

To describe Aβ-specific antibody titers as measured by peak concentration and area under the concentration curve (AUC) of antibody titers.
Open or close this module Eligibility
Minimum Age: 60 Years
Maximum Age: 75 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: Yes
Criteria:

Inclusion Criteria:

  • 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 and cognitively unimpaired as evaluated by memory tests performed at screening.
  • Homozygous APOE4 genotype.
  • Participant's willingness to have a study partner.

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.
  • 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 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, not as a result of a temporary condition.
  • Current clinically significant ECG findings.
Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: +41613241111
Central Contact Backup: Novartis Pharmaceuticals
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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