NCT07221344招募中1 期
A Phase 1/2a Placebo-Controlled Dose-Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-MAPT-SC in Healthy Subjects and Subjects With Early Alzheimer's Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 112
- 试验地点
- 5
- 主要终点
- Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time
研究概览
简要总结
Study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of ARO-MAPT-SC compared to placebo in adult healthy volunteers and in participants with early Alzheimer's disease (AD), defined as mild cognitive impairment due to AD and mild AD dementia.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •(All Participants):
- •Body mass index between 18.0 and 35.0 kilograms (kg)/square meter (m^2) at Screening
- •Not pregnant or breast-feeding
- •Able and willing to provide written informed consent prior to the performance of any study specific procedures
- •Participants of childbearing potential must agree to use highly effective contraception in addition to a condom during the study and for at least 90 days following the end of the study or last dose of study drug, whichever is later; participants must not donate sperm or eggs during the study and for at least 90 days following the end of the study or last dose of study drug whichever is later
- •Inclusion Criteria (Alzheimer's Disease):
- •Adults aged 50 to 80 years of age with a clinical diagnosis of early AD and plasma, CSF, or imaging biomarkers consistent with the diagnosis
- •If participant is on non-disease-modifying AD medications, the doses must be stable for ≥weeks prior to Screening.
- •Participants with early AD are not required to be on AD medications.
- •Participants previously treated or currently receiving anti-amyloid therapies, including lecanemab and donanemab, are not eligible.
- •Have a reliable and competent caregiver or trial partner who is ≥18 years of age, able and willing to accompany the participant to study visits involving informant-based assessments, to be available to site staff by telephone as needed, and in the opinion of the Investigator, be sufficiently familiar with the participant throughout the study in order to provide accurate and reliable information relevant to study outcome measures
排除标准
- •(All Participants):
- •Blood pressure outside of specified range in the protocol
- •Human immunodeficiency virus (HIV) infection (seropositive at Screening)
- •Seropositive for hepatitis B (HBV) or hepatitis C (HCV) at Screening
- •Intellectual disability or significant behavioral neuropsychiatric manifestation
- •Clinically significant cardiac, liver, or renal disease
- •Any contraindications to lumbar puncture
- •Known allergy or possible allergy to either ARO-MAPT-SC or to its excipients
- •Note: Additional inclusion/exclusion criteria may apply per protocol.
研究组 & 干预措施
ARO-MAPT-SC
Experimental
ARO-MAPT-SC injection
干预措施: ARO-MAPT-SC (Drug)
Placebo
Placebo Comparator
Sterile normal saline (0.9%)
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time
时间窗: Through End of Study (EOS; Day 315)
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) Over Time
时间窗: Through End of Study (EOS), Day 270
次要结局
- Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time(Baseline through EOS (Day 315))
- Change from Baseline in Glucose in CSF Over Time(Baseline through EOS (Day 315))
- Change from Baseline in Cell Count in CSF Over Time(Baseline through EOS (Day 315))
- PK of ARO-MAPT-SC: Maximum Observed Plasma Concentration (Cmax)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: Time to Maximum Plasma Concentration (Tmax)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: Area Under the Plasma Concentration (AUC) Versus Time Curve From Time Zero to 24 Hours (AUC0-24)(Through 24 hours postdose)
- PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero to 48 Hours (AUC0-48)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUC0-t)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: AUC Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf)(Through 48 hours post-dose)
- PK of ARO-MAPT-SC: Apparent Terminal Elimination Half-life (t1/2)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: Apparent Systemic Clearance (CL/F)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: Apparent Terminal-phase Volume of Distribution (Vz/F)(Through 48 hours postdose)
- PK of ARO-MAPT-SC: Amount Excreted (Ae) of Unchanged Drug in Urine From Time Zero to 24 Hours Postdose(Through 24 hours postdose)
- PK of ARO-MAPT-SC: Percentage of Administered Drug Recovered (Fe) in Urine From Time Zero to 24 Hours Postdose(Through 24 hours postdose)
- PK of ARO-MAPT-SC: Renal Clearance (CLR)(Through 24 hours postdose)
- Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time(Baseline through EOS, Day 270)
- Change from Baseline in Glucose in CSF Over Time(Baseline through EOS, Day 270)
- Change from Baseline in Cell Count in CSF Over Time(Baseline through EOS, Day 270)
研究者
研究点 (5)
Loading locations...
相似试验
已完成
1 期
HDAC Inhibitor Vorinostat (SAHA) With Capecitabine (Xeloda) Using a New Weekly Dose Regimen for Advanced Breast CancerAdvanced Breast CancerNCT00719875Yale University24
进行中（未招募）
2 期
HM15136 (Efpegerglucagon) Treatment for 8 Weeks in Subjects Aged ≥2 Years With Congenital Hyperinsulinism (CHI)Congenital HyperinsulinismNCT04732416Hanmi Pharmaceutical Company Limited17
进行中（未招募）
1 期
A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)Lymphoma, B-CellSmall Lymphocytic LymphomaWaldenstrom MacroglobulinemiaDiffuse Large B Cell LymphomaRichter's TransformationMarginal Zone LymphomaChronic Lymphocytic LeukemiaFollicular LymphomaMantle Cell LymphomaNCT03162536ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)190
已完成
1 期
Multiple Ascending Dose Study of TD-1439 in Healthy Adult and Elderly SubjectsHealthy Adults, Elderly SubjectsNCT02954263Theravance Biopharma40
已完成
1 期
Multiple Ascending Dose Study of TD-0714 in Healthy and Elderly SubjectsHealthy Adults, Elderly SubjectsNCT02709928Theravance Biopharma50