A study to investigate the safety and effectiveness of SAR448851 in participants with early Alzheimer's disease

INTERVENTION: Product Name: SAR448851, Product Code:PRD13501762, Pharmaceutical Form: CAPSULE, HARD, Other descriptive name: , Strength: , Product Name: Matched placebo for test product SAR448851, Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A , Product Name: MK‐6240, Product Code:PRD13429348, Pharmaceutical Form: SOLUTION FOR INJECTION, Other descriptive name: , Strength: , Product Name: SAR448851, Product Code:PRD13499817, Pharmaceutical Form: CAPSULE, HARD, Other descriptive name: , Strength: CONDITION: Dementia Alzheimer's type ; MedDRA version: 20.0Level: PTClassification code: 10012271Term: Dementia Alzheimer's type Class: 100000004852 Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: Part A and optional dose 2 cohort: To evaluate the effect of SAR448851 vs placebo on plasma p‐tau217, a fluid biomarker of Alzheimer's disease (AD). ; Part B: To evaluate the long‐term safety and tolerability of SAR448851. Primary end point(s): Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p‐tau217: From baseline to Week 48, Part B: Number of participants experiencing at least one TEAE: from Week 48 to Week 96 Secondary Objective: Part A and optional dose 2 cohort: To determine the effect of SAR448851 vs. placebo on additional key fluid and imaging biomarkers of AD., Part A and optional dose 2 cohort: To evaluate the effect of SAR448851 on target engagement., Part A and optional dose 2 cohort: To evaluate the safety and tolerability of SAR448851., Part A and optional dose 2 cohort: To characterize the pharmacokinetic (PK) of SAR448851., Part B: To evaluate the effect of SAR448851 on disease biomarkers from baseline to Week 96 for participants randomized to SAR448851 in Part A., Part B: To evaluate the effect of SAR448851 on disease biomarkers from Week 48 to Week 96 for all participants. SECONDARY OUTCOME: Secondary end point(s):Part A and optional dose 2 cohort: Change from baseline to Week 48 in brain amyloid plaque deposition as measured by amyloid positron emission tomography (PET): From baseline to Week 48 Secondary end point(s):Part A and optional dose 2 cohort: Change from baseline to Week 48 in CSF soluble triggering receptor expressed on myeloid cells 2 (sTREM2): From baseline to Week 48 Secondary end point(s):Part A and optional dose 2 cohort: Change from baseline to Week 48 in plasma glial fibrillary acidic protein (GFAP) and cerebrospinal fluid (CSF) neurogranin (Ng): From baseline to Week 48 Secondary end point(s):Part A and optional dose 2 cohort: Number of participants with ARIA‐E and ARIA‐H assessed by brain MRIs: From baseline to Week 48 Secondary end point(s):Part A and optional dose 2 cohort: Number of participants with TEAEs and serious adverse events (SAEs), and discontinuations due to TEAEs and SAEs (including laboratory assessments, vital sign measurements, ECGs and the CSSRS): From baseline to Week 48 Secondary end point(s):Part A and optional dose 2 cohort: Plasma and CSF concentrations of SAR448851: From baseline to Week 48 Secondary end point(s):Part B: Change from baseline to Week 96 in AD biomarkers: plasma p‐tau217, plasma GFAP, CSF Ng: From baseline to Week 96 Secondary end point(s):Part B: Change from Week 48 to Week 96 in AD biomarkers: plasma p‐tau217, plasma GFAP, CSF Ng: From Week 48 to Week 96 INCLUSION CRITERIA: Participant must be 55 to 85 years (inclusive) of age, at the time of signing the informed consent., Diagnosis of mild cognitive impairment (MCI) due to Alzheimer's disease (AD) (National Institute on Aging‐ Alzheimer’s Association [NIA‐AA] Stage 3) or mild AD dementia (NIA‐AA Stage 4)., Have a global Clinical Dementia Rating (CDR) score 0.5 to 1.0 and a CDR‐Memory Bo Xscore = 0.5 at screening., Have a study partner who must provide separate written informed consent at screening. Study partner should be >18 years of age, have known participant for at least 1 year, and have a minimum of 8 hours per week contact with participant., The participant has evidence of cerebral amyloid pathology confirmed by positive visual read on amyloid positron emission tomography (PET) at screening.