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
:
Recruiting
First Posted
: April 27, 2017
Last Update Posted
: April 2, 2018
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Alzheimer's Disease | Drug: CNP520 50mg Drug: CNP520 15mg Other: Placebo to CNP520 | Phase 2 Phase 3 |
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 : | Interventional (Clinical Trial) |
Estimated Enrollment : | 2000 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 |
Estimated Primary Completion Date : | July 30, 2024 |
Estimated Study Completion Date : | August 30, 2024 |

Arm | Intervention/treatment |
---|---|
Experimental: Arm#1: CNP520 50 mg
CNP520 50 mg capsule given p.o.
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Drug: CNP520 50mg
Arm#1
Other Name: 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 Name: CNP520 15 mg capsule p.o. for the duration of Treatment Epoch
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Placebo Comparator: Arm#3: Placebo
Placebo to CNP520 capsule given p.o.
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Other: Placebo to CNP520
Arm#3
Other Name: Placebo to CNP520 p.o. for the duration of Treatment Epoch
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- 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
- 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

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.
Ages Eligible for Study: | 60 Years to 75 Years (Adult, Senior) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | Yes |
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.

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
Contact: Novartis Pharmaceuticals | 1-888-669-6682 | trialandresults.registries@novartis.com | |
Contact: Novartis Pharmaceuticals | +41613241111 | info@generationprogram.com |

Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
Additional Information:
Responsible Party: | Novartis Pharmaceuticals |
ClinicalTrials.gov Identifier: | NCT03131453 History of Changes |
Other Study ID Numbers: |
CCNP520A2202J 2016-002976-28 ( EudraCT Number ) |
First Posted: | April 27, 2017 Key Record Dates |
Last Update Posted: | April 2, 2018 |
Last Verified: | March 2018 |
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 |
URL: | http:// |
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, Preclinical Alzheimer's Disease (AD), Aβ lowering, BACE-1 inhibitor |
Additional relevant MeSH terms:
Alzheimer Disease Dementia Brain Diseases Central Nervous System Diseases Nervous System Diseases |
Tauopathies Neurodegenerative Diseases Neurocognitive Disorders Mental Disorders |