A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of 48-week SAR448851 Treatment Followed by Open-label Extension in Participants With Early Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Sanofi
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217
研究概览
简要总结
This is a randomized, placebo-controlled Phase 2 study to evaluate the efficacy and safety of SAR448851 in early Alzheimer's disease (AD) participants. The purpose of this study is to measure efficacy and safety with once daily oral SAR448851 compared to placebo in participants with mild cognitive impairment due to AD or mild AD dementia and with evidence of cerebral amyloid pathology.
This Phase 2 study has 2 parts: Part A is a randomized, double-blind, parallel-group, placebo-controlled study with SAR448851 oral once daily. Part B is an open-label extension. All participants who complete Part A may continue to Part B. An optional dose 2 cohort will be considered to evaluate the efficacy and safety of SAR448851 dose 2 oral once daily.
The study duration will be up to 111 weeks for Part A and B, and up to 63 weeks for the dose 2 cohort. The treatment duration will be up to 96 weeks for Part A and B, and up to 48 weeks for the dose 2 cohort.
Up to 160 participants will be included in this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Part A and optional dose 2 cohort is a double-blind study in which participants, care providers, Treating Investigator, independent rater, clinical site staff, and Sponsor's clinical trial team members are blinded to study intervention. Part B is an open-label extension.
入排标准
- 年龄范围
- 55 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 Box score ≥ 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.
排除标准
- •The participant has any history of significant neurological disease including but not limited to, frontotemporal dementia, Lewy body dementia, Huntington's disease, serious infection of the brain, Parkinson's disease, multiple concussions, multiple sclerosis, or epilepsy or recurrent seizures (except febrile childhood seizures).
- •The participant has evidence of more than 4 microhemorrhages (<10 mm in diameter) or superficial siderosis.
- •The participant carries two copies of the apolipoprotein-E epsilon 4 (APOE4) allele (APOE4/4).
- •The participant is currently receiving or has previously received any anti-amyloid immunotherapy (including, but not limited to, aducanumab, lecanemab, or donanemab) or triggering receptor expressed on myeloid cells 2 (TREM-2) targeting therapy.
- •The participant is currently receiving anticoagulant therapies.
- •The participant has had malignancy in the 3 years prior to Screening, excluding basal cell carcinoma, squamous cell carcinoma of the skin, melanoma in situ, Stage 1 or 2 prostate cancer, fully resected renal cell cancers, or cervical carcinoma in situ that has been successfully treated.
- •The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
研究组 & 干预措施
SAR448851
Participants will receive SAR448851 dose 1 or dose 2 oral daily for 48 weeks
干预措施: SAR448851 (Drug)
Placebo
Participants will receive placebo oral daily for 48 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Part A and optional dose 2 cohort: change from baseline to Week 48 in plasma p-tau217
时间窗: From baseline to Week 48
Part B: Number of participants with treatment-emergent adverse events (TEAE), including ARIA-E and ARIA-H by brain MRI, laboratory assessments, vital sign measurements, ECGs and the C-SSRS
时间窗: From Week 48 to Week 96
Number of participants experiencing at least one treatment-emergent adverse event (TEAE), including amyloid-related imaging abnormalities with edema (ARIA-E) and amyloid-related imaging abnormalities with hemosiderin (ARIA-H) by brain magnetic resonance imaging (MRI), laboratory assessments, vital sign measurements, electrocardiograms (ECGs) and the Columbia-Suicide Severity Rating Scale (C-SSRS)
次要结局
- 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)
- 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)
- 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)
- 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 C-SSRS)(From baseline to Week 48)
- 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)
- Part A and optional dose 2 cohort: Plasma and CSF concentrations of SAR448851(From baseline to Week 48)
- Part B: Change from baseline to Week 96 in AD biomarkers: plasma p-tau217, plasma GFAP, CSF Ng(From baseline to Week 96)
- 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)