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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)

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ClinicalTrials.gov Identifier: NCT03131453
Recruitment Status : Completed
First Posted : April 27, 2017
Last Update Posted : March 17, 2021
Sponsor:
Collaborators:
Amgen
Banner Alzheimer's Institute
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Alzheimers Disease Drug: CNP520 50mg Drug: CNP520 15mg Other: Matching placebo Phase 2 Phase 3

Detailed Description:

The study was a randomized, double-blind, placebo-controlled, parallel group, adaptive design with variable treatment duration planned 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 received disclosure of their individual test results for APOE genotyping and brain amyloid status.

Treatment duration was variable (event driven trial) for at least 60 months, Participants returned 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 were conducted at month 6 and month 12, and on a yearly basis thereafter.

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

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

The study was terminated early ..provide reason...... The protocol was modified at termination and.................patients were followed, etc...

We need a reason why the two arms were combined

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1145 participants
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, 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).
Actual Study Start Date : August 3, 2017
Actual Primary Completion Date : March 26, 2020
Actual Study Completion Date : March 26, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: CNP520 50 mg
50 mg capsule taken orally once daily
Drug: CNP520 50mg
50 mg capsule

Experimental: CNP520 15 mg
15 mg capsule taken orally once daily
Drug: CNP520 15mg
15 mg capsule

Placebo Comparator: Placebo
Matching placebo to 15 and 50 mg CNP520 taken orally once daily
Other: Matching placebo
Matching placebo for 15 and 50 mg capsules




Primary Outcome Measures :
  1. 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

  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 demonstrate the effects of CNP520, vs. placebo on global clinical status

  2. 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

  3. 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

  4. 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)

  5. 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)

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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 could have prevented the participants 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 could 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 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, could have posed a risk to the participant, or could have prevented 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, was 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03131453


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Amgen
Banner Alzheimer's Institute
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Additional Information:
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03131453    
Other Study ID Numbers: CCNP520A2202J
2016-002976-28 ( EudraCT Number )
First Posted: April 27, 2017    Key Record Dates
Last Update Posted: March 17, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
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


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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Placebo controlled
APOE4 carriers
Homozygotes
Heterozygotes
Brain Amyloid
Aβ lowering
BACE-1 inhibitor
CNP520
adult
preclinical Alzheimers disease
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
CNP520
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action