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A Study of CAD106 and CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S1)

This study is currently recruiting participants.
See Contacts and Locations
Verified July 2017 by Novartis ( Novartis Pharmaceuticals )
Sponsor:
Collaborators:
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Amgen
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT02565511
First received: September 28, 2015
Last updated: July 31, 2017
Last verified: July 2017
  Purpose
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.

Condition Intervention Phase
Alzheimer's Disease Biological: CAD106 Immunotherapy Other: Placebo to CAD106 Drug: CNP520 Other: Placebo to CNP520 Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Time to diagnosis of MCI due to Alzheimer's Disease (AD) 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

  • 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:
  • 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, vs. respective placebo on global clinical status as measured by the change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score.

  • 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, 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 Columbia Suicide Severity Rating Scale (C-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.


  • Change on the Total Scale score and individual neurocognitive domain index scores of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) [ Time Frame: Baseline to Month 60 ]
    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.

  • Change in the Everyday Cognition scale (ECog) total scores [ Time Frame: Baseline to Month 60 ]
    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.

  • Change in Alzheimer's Disease related biomarkers [ Time Frame: Baseline to Months 24 and 60 ]

    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 18F-florbetapir obtained using brain positron emission tomography (PET) imaging, volumetric MRI measurements, and CSF Aβ40, Aβ42, total tau and phosphorylated tau181 levels.


  • Change in APCC Test Score and CDR-SOB [ 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.

  • Aβ-specific immune response [ Time Frame: Through study completion, an average of 5 years ]
    To describe Aβ-specific antibody titers and serological responder rates as measured by peak concentration and area under the concentration curve (AUC) of antibody titers.


Estimated Enrollment: 1340
Actual Study Start Date: December 3, 2015
Estimated Study Completion Date: August 27, 2023
Estimated Primary Completion Date: August 27, 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm#1
CAD106 (450 µg) + Alum (450 µg) given i.m. at week 1, 7, 13 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
Placebo to CAD106 + Alum (450 µg) given i.m. at week 1, 7, 13 and quarterly thereafter
Other: 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.
Experimental: Arm#3
CNP520 (50 mg) capsules oral intake (p.o.)
Drug: CNP520
CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch.
Placebo Comparator: Arm#4
Placebo to CNP520 capsules oral intake (p.o.)
Other: Placebo to CNP520
Placebo to CNP520 p.o. for the duration of the Treatment Epoch

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 Mild Cognitive Impairment 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 up to a maximum of 96 months and no longer than when the target number of events for the TTE endpoint has been observed and confirmed in either cohort.

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. Randomization will be stratified by age group (60-64 years, 65-75 years) and region (North America/Other , Europe).

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.

  Eligibility

Ages Eligible for Study:   60 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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.
  • 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 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.

For Cohort - II only:

• Participants with depigmenting or hypopigmenting conditions (e.g. albinism vitiligo) or active / history of chronic urticarial in the past year.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02565511

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

  Show 32 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Banner Alzheimer's Institute
National Institute on Aging (NIA)
Alzheimer's Association
Amgen
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02565511     History of Changes
Other Study ID Numbers: CAPI015A2201J
2015-002715-15 ( EudraCT Number )
Study First Received: September 28, 2015
Last Updated: July 31, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Randomization, Placebo controlled, Parallel-group, APOE4 Homozygotes, Preclinical Alzheimer's Disease (AD), Aβ lowering

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on August 17, 2017