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A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03131453
Recruitment Status : Active, not recruiting
First Posted : April 27, 2017
Last Update Posted : October 7, 2019
Sponsor:
Collaborators:
Amgen
Banner Alzheimer's Institute
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 5, 2017
First Posted Date  ICMJE April 27, 2017
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE August 3, 2017
Estimated Primary Completion Date July 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Time to event [ Time Frame: Through study completion, at least 5 years ]
    Event is defined as diagnosis of MCI due to AD or dementia due to AD, whichever occurs first during the course of the study, after confirmation by the 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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03131453 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2018)
  • Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520, vs. placebo on global clinical status
  • 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 demonstrate the effects of CNP520, vs. placebo on cognition
  • Change in the Everyday Cognition scale (ECog) total scores [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520, vs. placebo on function reported by the participant and study partner, respectively
  • Change in cerebral amyloid angiopathy (CAA) [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the effects of CNP520 vs placebo on CAA, as measured by Magnetic Resonance Imaging (MRI)
  • Change on volume of brain regions [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520 vs placebo on brain atrophy, as measured by volumetric Magnetic Resonance Imaging (MRI)
  • Change in amyloid deposition as measured by standardized uptake ratio (SUVR) of positron emission tomography (PET) scan with amyloid radiotracer [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Change in CSF levels of Aβ40, Aβ42 [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Change in CSF levels of total tau and phosphorylated tau [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Number of participants with adverse events as a measure of safety [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the safety and tolerability of CNP520 vs placebo
  • Change in neurofibrillary tangle burden as measured by standardized uptake ratio (SUVR) of PET scans with tau radiotracer (where available) [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
Original Secondary Outcome Measures  ICMJE
 (submitted: April 24, 2017)
  • Change in Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520, vs. placebo on global clinical status
  • 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 demonstrate the effects of CNP520, vs. placebo on cognition
  • Change in the Everyday Cognition scale (ECog) total scores [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520, vs. placebo on function reported by the participant and study partner, respectively
  • Change in cerebral amyloid angiopathy (CAA) [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the effects of CNP520 vs placebo on CAA, as measured by Magnetic Resonance Imaging (MRI)
  • Change on volume of brain regions [ Time Frame: Baseline to Month 60 ]
    To demonstrate the effects of CNP520 vs placebo on brain atrophy, as measured by volumetric Magnetic Resonance Imaging (MRI)
  • Change in amyloid deposition as measured by standardized uptake ratio (SUVR) of radiotracer positron emission tomography (PET) scan [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Change in CSF levels of Aβ40, Aβ42 [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Change in CSF levels of total tau and phosphorylated tau [ Time Frame: Baseline to Months 24 and 60 ]
    To demonstrate the effects of CNP520 vs placebo on Alzheimer's Disease-related biomarkers
  • Number of participants with adverse events as a measure of safety [ Time Frame: Through study completion, at least 5 years ]
    To demonstrate the safety and tolerability of CNP520 vs placebo
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease
Official Title  ICMJE A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of CNP520 in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (AD).
Brief Summary The purpose of this study is to determine the effects of CNP520 on cognition, global clinical status, and underlying AD pathology, as well as the safety of CNP520, in people at risk for the onset of clinical symptoms of AD based on their age, APOE genotype and elevated amyloid.
Detailed Description

The study uses a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration in approximately 2000 cognitively unimpaired participants aged 60 to 75 years, with at least one APOE4 allele (Homozygotes or Heterozygotes) and, if Heterozygotes, with evidence of elevated brain amyloid.

The screening period is expected to last about 12 weeks. Participants will receive disclosure of their individual test results for APOE genotyping and brain amyloid status.

Treatment duration is variable (event driven trial) for at least 60 months, and up to an expected maximum of 84 months.

Participants will return to the study site every three months for drug dispensing and every six months for safety and efficacy assessments, including neuropsychological scales with input from the study partner. Brain MRI scans will be conducted at month 6 and month 12, and on a yearly basis thereafter.

The Follow-up visit will be scheduled 12 weeks after the end of the Treatment Epoch. An additional CSF and / or PET AD biomarker assessments will be conducted on a voluntary basis at year 2 and 5.

The study (also known as the Generation Study 2) is conducted as part of the Alzheimer's Prevention Initiative (API) program.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • Drug: CNP520 50mg
    Arm#1
    Other Name: CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch
  • Drug: CNP520 15mg
    Arm#2
    Other Name: CNP520 15 mg capsule p.o. for the duration of Treatment Epoch
  • Other: Placebo to CNP520
    Arm#3
    Other Name: Placebo to CNP520 p.o. for the duration of Treatment Epoch
Study Arms  ICMJE
  • Experimental: Arm#1: CNP520 50 mg
    CNP520 50 mg capsule given p.o.
    Intervention: Drug: CNP520 50mg
  • Experimental: Arm#2: CNP520 15 mg
    CNP520 15 mg capsule given p.o.
    Intervention: Drug: CNP520 15mg
  • Placebo Comparator: Arm#3: Placebo
    Placebo to CNP520 capsule given p.o.
    Intervention: Other: Placebo to CNP520
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: October 3, 2019)
1145
Original Estimated Enrollment  ICMJE
 (submitted: April 24, 2017)
2000
Estimated Study Completion Date  ICMJE March 31, 2025
Estimated Primary Completion Date July 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if Heterozygotes, evidence of elevated brain amyloid.
  • Male or female, age 60 to 75 years inclusive. Females must be considered post-menopausal and not of child bearing potential
  • Cognitively unimpaired as evaluated by memory tests performed at screening.
  • Participant's willingness to have a study partner.
  • Carrier of at least one APOE4 gene if Heterozygotes, elevated brain amyloid (as measured by CSF Abeta or amyloid PET imaging).

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.
  • 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, not as a result of a temporary condition.
  • Current clinically significant ECG findings.
  • Clinically relevant depigmenting or hypopigmenting conditions (e.g. albinism, vitiligo) or active / history of chronic urticaria in the past year.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Puerto Rico,   Argentina,   Australia,   Belgium,   Canada,   Chile,   China,   Finland,   France,   Germany,   Iceland,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   Portugal,   Singapore,   South Africa,   Spain,   Switzerland,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03131453
Other Study ID Numbers  ICMJE CCNP520A2202J
2016-002976-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
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

URL: https://www.clinicalstudydatarequest.com
Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE
  • Amgen
  • Banner Alzheimer's Institute
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP