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History of Changes for Study: NCT03131453
A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S2)
Latest version (submitted August 4, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 April 24, 2017 None (earliest Version on record)
2 August 11, 2017 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 September 6, 2017 Study Status and Contacts/Locations
4 October 5, 2017 Contacts/Locations and Study Status
5 November 6, 2017 Contacts/Locations and Study Status
6 December 1, 2017 Contacts/Locations and Study Status
7 January 12, 2018 Study Status and Contacts/Locations
8 February 5, 2018 Contacts/Locations and Study Status
9 March 12, 2018 Contacts/Locations, Study Status, Outcome Measures, Eligibility and Study Description
10 March 29, 2018 Contacts/Locations, Study Status and References
11 May 4, 2018 Study Status and Contacts/Locations
12 June 6, 2018 Study Status and Contacts/Locations
13 July 3, 2018 Study Status and Contacts/Locations
14 July 17, 2018 Study Status and Contacts/Locations
15 August 6, 2018 Study Status and Contacts/Locations
16 September 14, 2018 Contacts/Locations and Study Status
17 October 2, 2018 Contacts/Locations, Study Status and IPDSharing
18 October 4, 2018 Contacts/Locations and Study Status
19 October 16, 2018 Contacts/Locations and Study Status
20 October 30, 2018 Contacts/Locations and Study Status
21 December 7, 2018 Contacts/Locations and Study Status
22 January 25, 2019 Contacts/Locations and Study Status
23 February 4, 2019 Contacts/Locations and Study Status
24 March 7, 2019 Contacts/Locations and Study Status
25 March 24, 2019 Contacts/Locations and Study Status
26 May 14, 2019 Contacts/Locations, IPDSharing and Study Status
27 July 16, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
28 September 30, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
29 October 3, 2019 Recruitment Status, Contacts/Locations, Study Status and Study Design
30 February 15, 2020 Contacts/Locations, Study Status and Study Design
31 July 22, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Design
32 July 27, 2020 Contacts/Locations and Study Status
33 August 18, 2020 Study Status
34 December 21, 2020 Study Status
35 March 14, 2021 Arms and Interventions, Conditions, Study Status, IPDSharing, Eligibility and Study Description
36 March 25, 2021
Quality Control Review has not concluded Returned: April 23, 2021
Contacts/Locations, Outcome Measures, Study Status, Study Description, Document Section, Conditions and Study Identification
37 May 18, 2021
Quality Control Review has not concluded Returned: June 11, 2021
Outcome Measures, Contacts/Locations, Study Status and Study Description
38 June 30, 2021
Quality Control Review has not concluded Returned: July 20, 2021
Recruitment Status, Outcome Measures, Study Status, Study Description
39 August 4, 2021 Study Status, Outcome Measures
Comparison Format:

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Study NCT03131453
Submitted Date:  April 24, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: CCNP520A2202J
Brief Title: A Study of CNP520 Versus Placebo in Participants at Risk for the Onset of Clinical Symptoms of Alzheimer's Disease (Generation S2)
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).
Secondary IDs: 2016-002976-28 [EudraCT Number]
Open or close this module Study Status
Record Verification: April 2017
Overall Status: Not yet recruiting
Study Start: June 22, 2017
Primary Completion: July 30, 2024 [Anticipated]
Study Completion: July 30, 2024 [Anticipated]
First Submitted: April 5, 2017
First Submitted that
Met QC Criteria:
April 24, 2017
First Posted: April 27, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
April 24, 2017
Last Update Posted: April 27, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Novartis Pharmaceuticals
Responsible Party: Sponsor
Collaborators: Amgen
Banner Alzheimer's Institute
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.

Open or close this module Conditions
Conditions: Alzheimer's Disease
Keywords: Placebo controlled,
APOE4 carriers,
Homozygotes,
Heterozygotes,
Brain Amyloid,
Preclinical Alzheimer's Disease (AD),
Aβ lowering,
BACE-1 inhibitor
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: 3
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 2000 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm#1: CNP520 50 mg
CNP520 50 mg capsule given p.o.
Drug: CNP520 50mg
Arm#1
Other Names:
  • CNP520 50 mg capsule p.o. for the duration of the Treatment Epoch
Experimental: Arm#2: CNP520 15 mg
CNP520 15 mg capsule given p.o.
Drug: CNP520 15mg
Arm#2
Other Names:
  • CNP520 15 mg capsule p.o. for the duration of Treatment Epoch
Placebo Comparator: Arm#3: Placebo
Placebo to CNP520 capsule given p.o.
Placebo to CNP520
Arm#3
Other Names:
  • Placebo to CNP520 p.o. for the duration of Treatment Epoch
Open or close this module Outcome Measures
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 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
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
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:

  • 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 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.
Open or close this module Contacts/Locations
Central Contact Person: Novartis Pharmaceuticals
Telephone: 1-888-669-6682
Email: trialandresults.registries@novartis.com
Central Contact Backup: Novartis Pharmaceuticals
Telephone: +41613241111
Study Officials: Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes

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

Supporting Information:
Time Frame:
Access Criteria:
URL:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services