Alzheimer's disease MedDRA version: 19.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: CNP520 15 mg
Product Code: CNP520
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not established
Current Sponsor
Sponsors
Novartis Farmacéutica S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Screening part I: Participants eligible for inclusion must fulfill all of the following criteria prior to scheduling the genetic disclosure. 1. Written informed consent must be obtained before any assessment is performed as part of the study, including consent to receive disclosure of their risk estimates to develop clinical symptoms of AD based on their APOE genotype and, if HTs, with evidence of elevated brain amyloid. 2. Male or female, age 60-75 years inclusive, at the time of signing the informed consent. To ensure that no more than 20% of participants in the age group 60-64 years are randomized across the whole recruitment period, a site level process will be implemented. 3. Females must be considered post-menopausal and not of child bearing potential i.e. they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. history of vasomotor symptoms), or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation. 4. Intellectually, visually and auditorily capable, fluent in, and able to read, the language in which study assessments are administered (e.g. completion of at least 6 years of regular schooling or sustained employment or equivalent local level of knowledge). 5. Mini-Mental State Examination total score =24. 6. Willing to have a study partner throughout the study. N.B. Buccal swab and genetic disclosure do not need to be repeated if already performed within the API015A2201J study. Screening part II: Participants eligible for inclusion must fulfill all of the following criteria prior to randomization based on the results from the screening test procedures. 7. Carrier of at least one e4 allele of the APOE gene: HMs with elevated or not elevated brain amyloid OR HTs with elevated brain amyloid (as measured by CSF Aß or amyloid PET imaging). Evidence of elevated brain amyloid can be waived if images are available from a previous amyloid PET scan and can be sent for visual (qualitative) assessment by the central reader. Note: In cases where both CSF Aß and amyloid PET imaging tests are performed, at least one should be indicative of elevated brain amyloid. 8. Cognitively unimpaired at screening visit as defined by: Score of 85 or greater on the RBANS delayed memory index score AND CDR global score of 0 with two special exceptions: a) If the RBANS delayed memory index score is between 70 and 84 (inclusive) AND the global CDR = 0, the participant may be allowed to continue ONLY if the investigator judges that cognition is unimpaired following review of the MCI/dementia criteria; b) If the global CDR score = 0.5 AND the RBANS delayed memory index score is 85 or greater, the participant may be allowed to continue ONLY if the investigator judges that cognition is unimpaired following review of the MCI/dementia criteria. 9. Having a study partner who agrees to participate in the study and who is intellectually, visually, and auditorily capable, and fluent in, and able to read, the language in which study assessments are administered. Additionally, the study partner must be capable of and willing to: a) Accompany the participant to visits that requires the input of the study partner; b) Meet
Exclusion criteria
Exclusion criteria: Screening part I: Participants will be excluded if they fulfill any of the following criteria prior to scheduling the genetic disclosure. 1. Current medical or neurological condition that might impact cognition or performance on cognitive assessments e.g. MCI, dementia, Huntington’s or Parkinson’s disease etc. 2. Advanced, severe progressive or unstable disease that may interfere with the safety, tolerability and study assessments, or put the participant at special risk e.g. active hepatitis, HIV infection, severe renal impairment, severe hepatic impairment etc. 3. History of malignancy of any organ system, treated or untreated, within the past 60 months, regardless of whether there is evidence of local recurrence or metastases. However, localized nonmalignant tumors not requiring systemic chemo- or radio-therapy, localized basal or squamous cell carcinoma of the skin, or in-situ cervical cancer are permitted. 4. Current treatment with Cholinesterase Inhibitors and/or another AD treatment. 5. Clinically relevant depigmenting or hypopigmenting conditions or active/history of chronic urticaria in the past year. 6. Score “yes” on item 4 or 5 of the Suicidal Ideation section of the C-SSRS, if this ideation occurred in the past 6 months, or “yes” on any item of the Suicidal Behavior section, except for the “Non-Suicidal Self-Injurious Behavior”, if this behavior occurred in the past 2 years prior to screening. 7. Lacking psychological readiness to receive APOE genotype/amyloid status results, as assessed based on investigator’s judgement supported by the pre-disclosure rating scales: Geriatric Depression Scale total score >6; Six Item Subset Inventory of the modified State Trait Anxiety Inventory total score >17. 8. Use of other investigational drugs prior to screening until: Small molecules: after 5 half-lives, or within 30 days until the expected pharmacodynamic effect has returned to baseline, whichever is longer; Biologicals: blood concentration has returned to baseline (or below serological responder threshold) for antibodies induced by active immunotherapy; or 5 half-lives for monoclonal antibodies or other biologicals. 9. Treatment in the 4 weeks prior to randomization with any drug or treatment known for the potential to cause major organ system toxicity i.e. drugs that may require periodic safety monitoring of a specific organ or body fluid. Examples include but are not limited to clozapine, cancer medical treatment like tamoxifen, immunosuppressive drugs like methotrexate or interferon, or other biological medicines for rheumatic diseases or multiple sclerosis or associated with Torsades de pointes. 10. Current chronic treatment (>3 months) with: Strong CYP3A4 inducers or inhibitors; Drugs with a narrow therapeutic index known to be primarily metabolized by CYP2C or CYP3A isoenzymes and sensitive P-gp substrates. 11. Violations of concomitant medication restrictions. 12. Donation or loss of 400 mL or more of blood within 8 weeks prior to randomization. 13. Contraindication or intolerance to MRI investigations. Screening part II: Participants fulfilling any of the following criteria based on results from the screening test procedures will be excluded. 14. A positive drug screen, i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - To demonstrate the effect of CNP520 vs placebo on time to diagnosis of MCI due to AD or dementia due to AD, whichever occurs first during the course of the study. - To demonstrate the effect of CNP520 vs placebo on cognition using APCC. ; Secondary Objective: Key secondary objective: - To demonstrate the effects of CNP520 vs placebo on global clinical status. Secondary objectives: - To demonstrate the safety and tolerability of CNP520 vs placebo. - To demonstrate the effects of CNP520 vs placebo on cognition using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). - To demonstrate the effects of CNP520 vs placebo on function. - To demonstrate the effects of CNP520 vs placebo on Magnetic Resonance Imaging (MRI) measures suggestive of cerebral amyloid angiopathy (CAA). - To demonstrate the effects of CNP520 vs placebo on brain atrophy. - To demonstrate the effects of CNP520 vs placebo on AD-related biomarkers. ; Primary end point(s): - Time to the first event with event defined as the first confirmed diagnosis of MCI due to AD or dementia due to AD. - Change from baseline to month 60 in APCC score. ; Timepoint(s) of evaluation of this end point: - Baseline to month 60. - Baseline to month 60. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Change from baseline to month 60 in Clinical Dementia Rating Scale - Sum of Boxes (CDRSOB) score. - Frequencies, changes from baseline, Kaplan-Meyer estimates when applicable of: Adverse events; Skin events based on a centralized dermatological monitoring; Safety findings from brain structural MRI central reader; Laboratory tests; Vital signs; ECG findings; Prospective suicidality assessment (ideation and behavior) from eC-SSRS. - Change from baseline to month 60 in total RBANS score and individual neurocognitive domain index scores. - Change from baseline to month 60 in total score of the Everyday Cognitive (ECog) scale: ECogsubject and ECog-informant. -Number, intensity and location of microhemorrhages and white matter hyperintensities using the Wahlund scale, both as assessed by central MRI reader. -Change from baseline to month 60 on volume of brain regions as measured by volumetric MRI. -Change from baseline to 24 and 60 months on: amyloid deposition as measured by standardized uptake ratio (SUVR) of radiotracer positron emission tomography (PET) scan; CSF levels of Aß40, Aß42; neurodegeneration as measured by CSF levels of total tau and phosphorylated tau. Collected only in participants who consented to additional voluntary procedures ; Timepoint(s) of evaluation of this end point: - Baseline to month 60. - Baseline to month 60. - Baseline to month 60. - Baseline to month 60. | — |
Countries
Argentina, Austria, Belgium, Canada, Chile, China, Finland, France, Germany, Hong Kong, Iceland, Israel, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Portugal, Singapore, South Africa, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactDepartamento Médico
Novartis Farmacéutica S.A
Outcome results
None listed