A Phase I, Randomized, Double-Blind Study to Evaluate the Safety and Tolerability of AV-1980R in Participants With Preclinical Alzheimer's Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 48
- 试验地点
- 6
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events and Serious Adverse Events
研究概览
简要总结
This is a Phase 1, multicenter, randomized, double-blind, placebo-controlled, multiple-dose-escalation study evaluating the safety, tolerability, and immunogenicity of AV-1980R, an investigational vaccine targeting pathological tau, in participants with preclinical Alzheimer's disease. Up to 48 cognitively unimpaired adults aged 65 to 80 years with biomarker evidence of preclinical Alzheimer's disease will be enrolled into three ascending-dose cohorts.
详细描述
This study will evaluate AV-1980R, a MultiTEP-based active immunotherapy formulated with Advax-CpG55.2 adjuvant, in participants with preclinical Alzheimer's disease. Up to 48 participants aged 65 to 80 years will be randomized in a 3:1 ratio to receive AV-1980R or placebo in three ascending-dose cohorts of 20 µg, 60 µg, and 180 µg.
Participants will receive three intramuscular injections at Weeks 0, 4, and 38, with follow-up visits through Week 58. The primary objective is to evaluate safety and tolerability. Secondary objectives include evaluation of anti-tau antibody responses and T-cell responses. Exploratory assessments include plasma Alzheimer's disease biomarkers, tau PET imaging, immune-response characteristics, and cognitive measures.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The study is double-blind. Participants and clinical staff administering the investigational product will not know whether AV-1980R or placebo was assigned. The randomization schedule will be maintained in the interactive response technology system, and the AV-1980R and placebo vials will be masked to maintain the blind. Emergency unblinding is permitted only when treatment assignment is necessary for the participant's medical care.
入排标准
- 年龄范围
- 65 Years 至 80 Years（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or postmenopausal or surgically sterile female, 65 to 80 years of age, inclusive.
- •Cognitively unimpaired participant with preclinical Alzheimer's disease who meets all of the following:
- •Clinical Dementia Rating global score of 0 at Screening. Mini-Mental State Examination score ≥26, with education adjustment at Screening.
- •Plasma p-tau217/Aβ42 ratio ≥0.00738 measured using Lumipulse (Fujirebio). A prior positive result obtained within 12 months before Screening may be accepted but must be confirmed by the central laboratory.
- •Sight and hearing, including use of a hearing aid, sufficient to comply with study procedures.
- •Stable concomitant medications. Participants receiving fluctuating medication or treatment may be considered if the underlying condition is controlled.
- •Signed informed consent before any study-related procedure. Ability, in the Investigator's opinion, to understand the study and comply with protocol requirements.
排除标准
- •Screening MRI showing any of the following:
- •More than one noncortical lacunar infarct greater than 1.5 cm. Any territorial infarct greater than 1.5 cm. Combined microbleeds and areas of leptomeningeal hemosiderosis greater than 5, or disseminated leptomeningeal hemosiderosis.
- •Any other significant cerebral abnormality, including ARIA-E. Contraindication to MRI, including non-MRI-safe implanted metallic devices or clinically significant claustrophobia.
- •Serious illness requiring systemic treatment or hospitalization within 4 weeks before study entry.
- •Clinically relevant cardiovascular, respiratory, gastrointestinal, endocrine, immunologic, hematologic, systemic disease, or major surgery that could interfere with participation or follow-up.
- •Insulin-dependent diabetes. Clinically relevant cardiac arrhythmia, palpitation, conduction abnormality, prolonged QT interval, or bundle branch block.
- •Pre-existing autoimmune disease. C-SSRS score of 3 or higher. History of seizure disorder, except permitted stable use of certain antiepileptic medications for chronic pain.
- •Any medical, psychological, or social condition that could interfere with participation, compliance, or participant 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 tau or amyloid-beta immunotherapy within 1 year before Screening. Use of specified immunomodulatory or growth-stimulating treatments within 30 days before study entry.
- •Chronic use for more than 3 months of warfarin, other coumarin derivatives, anticoagulants, or an antiplatelet agent such as clopidogrel.
- •Parenteral immunoglobulin preparations, blood products, or plasma derivatives. History of severe local or systemic vaccination reactions or significant allergic reactions.
- •Clinically significant laboratory abnormalities at Screening, including ALT or AST greater than 1.5 times the upper limit of normal.
- •Positive testing for HIV-1 or HIV-2, hepatitis B surface antigen, or hepatitis C.
研究组 & 干预措施
AV-1980R 60 µg Arm
Participants receive 60 µg of AV-1980R formulated with Advax-CpG55.2 by intramuscular injection at Weeks 0, 4, and 38.
干预措施: AV-1980R 60 µg (Biological)
AV-1980R 180 µg Arm
Participants receive 180 µg of AV-1980R formulated with Advax-CpG55.2 by intramuscular injection at Weeks 0, 4, and 38.
干预措施: AV-1980R 180 µg (Biological)
Placebo Arm
Participants receive 10 mM phosphate buffer without active AV-1980R, formulated with Advax-CpG55.2, by intramuscular injection at Weeks 0, 4, and 38.
干预措施: Placebo (Other)
AV-1980R 20 µg Arm
Participants receive 20 µg of AV-1980R formulated with Advax-CpG55.2 by intramuscular injection at Weeks 0, 4, and 38.
干预措施: AV-1980R 20 µg (Biological)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events and Serious Adverse Events
时间窗: Baseline through Week 58
Number of participants who experience one or more treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs), summarized by severity and relationship to study intervention.
次要结局
- Number of Participants with Clinically Significant Changes in Neurological Examinations(Screening through Week 58)
- Number of Participants with Clinically Significant Changes in Vital Signs(Baseline through Week 58)
- Number of Participants with Clinically Significant Changes in ECG Results(Baseline through Week 58)
- Number of Participants with Clinically Significant Changes in Laboratory Tests(Baseline through Week 58)
- Number of Participants with Clinically Significant Changes in Physical Examinations(Screening through Week 58)
- Number of Participants with New MRI Abnormalities, Including ARIA-E and ARIA-H(Screening and Weeks 6, 40, and 58)
- Change from Baseline in Columbia-Suicide Severity Rating Scale Assessment(Baseline and Weeks 38, 40, 50, and 58)
- Change from Baseline in Serum Anti-Tau Antibody Titers(Baseline through Week 58)
- Change from Baseline in MultiTEP-Specific T-Helper Cell Responses(Baseline through Week 58)
- Change from Baseline in Tau-Specific Autoreactive T-Helper Cell Responses(Baseline through Week 58)