A Phase II, Randomized, Double-Blind Study to Evaluate Safety, Tolerability, Immunogenicity, and Amyloid-Lowering Effect of Amyloid-β Vaccine, AV-1959R, in Individuals With Preclinical Alzheimer's Disease.
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 160
- 主要终点
- Change From Baseline in C-SSRS Score
研究概览
简要总结
This Phase 2 study will evaluate the safety, tolerability, immunogenicity, and amyloid-lowering effect of AV-1959R in cognitively unimpaired adults with preclinical Alzheimer's disease. Approximately 160 participants will be randomized to receive AV-1959R or placebo and will be followed for 78 weeks. The study will assess safety, immune responses, brain amyloid, and Alzheimer's disease-related biomarkers.
详细描述
This Phase 2 study is designed to further evaluate AV-1959R in cognitively unimpaired individuals with preclinical Alzheimer's disease, with emphasis on safety, tolerability, immunogenicity, and surrogate efficacy based on changes in Alzheimer's disease-related biomarkers and amyloid pathology
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Investigator)
盲法说明
Participants and investigators will remain blinded to treatment assignment.
入排标准
- 年龄范围
- 55 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants 55 to 80 years of age, inclusive, at screening. Signed informed consent before initiation of study-related procedures.
- •Cognitively unimpaired participants with preclinical Alzheimer's disease meeting all of the following:
- •CDR global score = 0 at screening. MMSE score ≥26 at screening, with education adjustment. Plasma p-tau217/Aβ1-42 ratio ≥0.
- •Vision and hearing sufficient to comply with study procedures, in the investigator's judgment.
- •Stable concomitant medications for management of existing medical conditions, as appropriate.
- •Women must be of non-childbearing potential as defined in the protocol. Men must meet protocol-defined contraception and sperm donation requirements. Ability, in the investigator's opinion, to understand the study and comply with study requirements.
排除标准
- •Screening MRI showing clinically significant abnormalities, including protocol-defined infarcts, excessive microbleeds, leptomeningeal hemosiderosis, superficial siderosis, or ARIA-E.
- •Contraindication to MRI. Serious illness requiring systemic treatment and/or hospitalization within 4 weeks before study entry.
- •Clinically relevant cardiovascular, respiratory, gastrointestinal, endocrine, immunologic, hematologic, neurologic, or other systemic disease that could interfere with participation or follow-up.
- •Insulin-dependent diabetes. Clinically significant ECG abnormalities, including protocol-defined conduction abnormalities or QTc abnormalities.
- •Pre-existing autoimmune disease. History of seizure disorder, except protocol-permitted use of certain antiepileptic medications for chronic pain.
- •Any medical, psychological, or social condition that may interfere with participation, compliance, or safety.
- •Participation in another investigational drug study or use of an investigational drug within 30 days or 5 half-lives, whichever is longer, before dosing.
- •Prior amyloid-beta or tau immunotherapy, including vaccine or monoclonal antibody, within 1 year before screening.
- •Recent use of protocol-defined immunomodulatory or growth-stimulating agents. Chronic use of protocol-defined anticoagulants or antiplatelet agents; aspirin is permitted.
- •Parenteral use of immunoglobulin preparations, blood products, or plasma derivatives.
- •History of severe local or systemic vaccine reactions or significant allergic reactions.
- •Clinically significant laboratory abnormalities at screening. Positive testing for HIV-1/2, hepatitis B surface antigen, or hepatitis C virus.
研究组 & 干预措施
Placebo
Participants will receive placebo with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
干预措施: Placebo (Drug)
AV-1959R
Participants will receive AV-1959R 100 micrograms with adjuvant by intramuscular injection at Weeks 0, 4, and 44.
干预措施: AV-1959R (Biological)
结局指标
主要结局
Change From Baseline in C-SSRS Score
时间窗: Baseline through Week 78
Change from baseline in Columbia-Suicide Severity Rating Scale score comparing AV-1959R and placebo groups.
Clinically Significant Changes in Safety Assessments
时间窗: Through Week 78
Number and percentage of participants with clinically significant changes in vital signs, ECG, laboratory assessments, physical examinations, or neurological examinations.
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: From first study intervention through Week 78
Number and percentage of participants with treatment-emergent adverse events.
Incidence of ARIA-E and ARIA-H
时间窗: Through Week 78
Number and percentage of participants with MRI-detected amyloid-related imaging abnormalities, including ARIA-E and ARIA-H.
Serum Anti-Amyloid-Beta Antibody Levels
时间窗: Baseline through Week 78
Serum anti-amyloid-beta antibody levels following vaccination, comparing AV-1959R and placebo groups.
次要结局
- T-cell responses to MultiTEP and amyloid-beta(Baseline through Week 78)
- Change From Baseline in Global Brain Amyloid Burden(Baseline to Week 78)
- Change From Baseline in Plasma p-tau217/Aβ1-42 Ratio(Baseline through Week 78)