NCT04619420终止2 期
A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With a Long-Term Extension Treatment Period to Assess the Efficacy and Safety of JNJ-63733657, an Anti-tau Monoclonal Antibody, in Participants With Early Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 523
- 试验地点
- 188
- 主要终点
- Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104
研究概览
简要总结
The primary purpose of this study is to evaluate the effect of JNJ-63733657 versus placebo on clinical decline as measured by the Integrated Alzheimer's Disease Rating Scale (iADRS), a composite of cognition and function.
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)
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
- •Early Alzheimer's disease (AD): Gradual and progressive subjective decline in the participant's cognition over at least the past 6 months, as reported by the participant and informant (study partner) and Clinical Dementia Rating-Global Score (CDR-GS) of 0.5 and memory box score greater than or equal to (>=) 0.5 at screening
- •Participants must have positive tau PET results
- •Able to read and write and with a minimum 5 years of formal education as reported by participant and study partner at screening
- •Have a designated study partner who has adequate literacy to participate and be judged to have high likelihood of completing the study with the participant
- •Male participants must agree not to donate sperm for the purpose of reproduction during the study and up to 16 weeks after receiving the last dose of study intervention
排除标准
- •Participants with CDR GS >=2 at predose baseline Clinical Dementia Rating (CDR) administration
- •Participants who fulfill diagnostic criteria for Mild Cognitive Impairment (MCI) or dementia/mild or major neurocognitive disorder suspected to be due to any etiology other than AD (example, Parkinson's disease, cerebrovascular disease, normal pressure hydrocephalus, head injury, drug or alcohol abuse/dependence, anoxic brain injury, (Et cetera[etc])
- •Geriatric Depression Scale (GDS) 30 score greater than (>) 12
- •Hachinski Ischemic Scale (HIS) >4
- •Has received medications that affect the central nervous system (CNS), except treatments for AD, for less than 2 months; that is, doses of chronic medications that effect the CNS should be stable for at least 2 months before the start of screening. If a participant has recently stopped a chronic medication that effects the CNS, he or she must have discontinued treatment at least 2 months before the start of screening. Chronic use of benzodiazepines is not permitted
研究组 & 干预措施
JNJ-63733657 High-dose
Experimental
Participants will receive single dose of JNJ-63733657 high-dose administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
干预措施: JNJ-63733657 (Drug)
JNJ-63733657 Low-dose
Experimental
Participants will receive single dose of JNJ-63733657 low-dose administered by intravenous (IV) infusion every 4 weeks during the double-blind treatment period. Participants will have an option to continue with the long-term extension (LTE) phase of the trial and will continue to receive the same treatment and dose during the LTE treatment period.
干预措施: JNJ-63733657 (Drug)
Placebo
Placebo Comparator
Participants will receive single dose of matching placebo to JNJ-63733657 administered by IV infusion every 4 weeks during double-blind treatment period. Participants will have an option to continue with the LTE phase of the trial and will be re-randomized in a 1:1 ratio to receive either JNJ-63733657 low-dose or JNJ-63733657 high-dose during the LTE treatment period.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Integrated Alzheimer's Disease Rating Scale (iADRS) Total Score at Week 104
时间窗: Week 104
The linear combination of the ADAS Cog13 and ADCS ADL MCI that serves as a composite of cognition and function (overall clinical status) of the participant and score range from 0 to 138 with lower scores indicating worse performance. The iADRS will be a combination of ADAS Cog13 (score 0 to 85, higher scores indicate worse cognitive performance) and ADCS-ADL MCI (yielding a score 0 to 53, lower scores indicate worse daily function).
次要结局
- Change From Baseline in Alzheimer's Disease Assessment Scale Cognitive subscale 13-item version (ADAS-Cog 13) Total Score at Week 104(Week 104)
- Change From Baseline in Brain tau Burden as Measured by tau PET at Week 104(Baseline, Week 104)
- Change From Baseline in Clinical Dementia Rating- Sum of Boxes (CDR-SB) at Week 104(Baseline, Week 104)
- Change From Baseline in Cerebrospinal Fluid (CSF) concentrations of Total, Free, and Bound p217+tau Fragments at Week 104(Baseline, Week 104)
- Serum Concentrations of JNJ-63733657(At Weeks 4, 8, 12, 16, 20, 24, 36, 52, 76, 104, 128, 156, 180, 208, 232 (End of treatment))
- Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability(Up to 245 Weeks)
- Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability(Up to 245 Weeks)
- Percentage of Participants Progressing From Clinical Dementia Rating- Global Score (CDR-GS) 0 to 0.5 or Higher, 0.5 to 1 or Higher, 1 to 2 or Higher, from Baseline to Post-baseline through Week 104(From Baseline through Week 104)
- Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living for Mild Cognitive Impairment (ADCS-ADL MCI) Total Score at Week 104(Week 104)
- Number of Participants with Physical and Neurological Examination Abnormalities(Up to 245 Weeks)
- Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Scale Index Score at Week 88(Baseline, Week 88)
- Change From Baseline in RBANS Indices at Week 88(Baseline, Week 88)
- Change from Baseline in Neuropsychiatric Inventory (NPI) at Week 104(Baseline, Week 104)
- CSF Concentrations of JNJ-63733657(At Weeks 52, 104, 208 (End of Treatment))
- Anti-Drug Antibody to JNJ-63733657(Up to 245 Weeks (90 days [+-7 days] after last dose of study intervention))
- Number of Participants with Treatment-Emergent Adverse Event of Special Interest (AESI)(Up to 245 Weeks)
- Number of Participants with Electrocardiogram (ECG) Abnormalities(Up to 245 Weeks)
- Number of Participants with Clinical Laboratory Abnormalities(Up to 245 Weeks)
- Percentage of Participants with Vital Sign Abnormalities(Up to 245 Weeks)
- Changes From Baseline in Brain Magnetic Resonance Imaging (MRI) Safety Findings(Baseline and Up to 4.5 years (End of treatment))
- Change From Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) score(Baseline and Up to 245 Weeks)
研究者
研究点 (188)
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相关资讯
Advances in Alzheimer's Disease Treatment: From Anti-Amyloid Antibodies to Multi-Target Strategies- Alzheimer's disease affects 55 million people worldwide, with prevalence reaching 20–30% in those aged 85 and older, and dementia cases are projected to hit 150 million by 2050.
- The FDA has granted traditional approval to lecanemab (2023) and donanemab (2024) for early symptomatic AD, while aducanumab received accelerated approval in 2021 amid controversy.
- As of January 2025, 182 clinical trials are evaluating 138 investigational agents, with 31 candidates in Phase 3 trials targeting amyloid, tau, neuroinflammation, and other pathways.
- Multi-target drugs such as blarcamesine and ALZ-801 show promise, while 46 repurposed agents represent 33% of all compounds in the current AD pipeline.3 months agoJ&J's Alzheimer's Therapies, Posdinemab and JNJ-2056, Receive FDA Fast Track Designation- Johnson & Johnson's posdinemab, a monoclonal antibody targeting phosphorylated tau, has received FDA Fast Track designation for early Alzheimer's treatment.
- JNJ-2056, an anti-tau active immunotherapy, also received Fast Track status, marking the second such designation for J&J's Alzheimer's portfolio in 2024.
- Both therapies are currently in Phase 2b trials, with posdinemab in the "AuTonomy" study and JNJ-2056 in the "ReTain" trial, aimed at slowing disease progression.
- The FDA's Fast Track designation is designed to expedite the review of drugs addressing serious conditions with unmet medical needs, potentially accelerating patient access.last year