NCT06672445进行中（未招募）1 期
A Phase 1 Placebo-Controlled Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ARO-ATXN2 in Adult Subjects With Spinocerebellar Ataxia Type 2
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 39
- 试验地点
- 16
- 主要终点
- Number of Participants with Treatment -Emergent Adverse Events (TEAEs) Over Time
研究概览
简要总结
Adult participants with spinocerebellar ataxia type 2 (SCA2) who carry ≥33 cytosine, adenine, guanine (CAG) repeats in the ATXN2 gene, and who have met all protocol eligibility criteria will be randomized to receive a single dose of ARO-ATXN2 or placebo and be evaluated for safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) parameters.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-pregnant, non-lactating
- •Diagnosis of symptomatic SCA2 and ≥33 CAG repeats in the ATXN2 gene based on source verifiable medical records or genetic testing at Screening
- •Scale of Assessment and Rating of Ataxia (SARA) score ≤14
- •Subjects 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. Subjects 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
排除标准
- •Uncontrolled hypertension (blood pressure >160/100 mmHg)
- •History of having received stem cell therapy
- •Clinically significant cardiac, liver, or renal disease
- •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
- •Any contraindications to lumbar puncture, including INR >1.4, platelet count <100,000, and use of anticoagulant or antiplatelet medications that cannot be safely interrupted
- •Presence of an implanted shunt for drainage of CSF or an implanted central nervous system (CNS) catheter
- •Note: Additional inclusion/exclusion criteria may apply per protocol.
研究组 & 干预措施
ARO-ATXN2
Experimental
ARO-ATXN2 Injection
干预措施: ARO-ATXN2 Injection (Drug)
Placebo
Placebo Comparator
(0.9% NaCl)
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 253
次要结局
- PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quatifiable Plasma Concentration (AUClast)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Elimination Half-life (t1/2)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Apparent Systemic Clearance (CL/F)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Recovery of Unchanged Drug Excreted in Urine (Ae)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Renal Clearance (CLr)(Through 24 hours post-dose)
- Percentage of Administered Drug Recovered in Urine(Through 24 hours post-dose)
- Change from Baseline in Glucose in CSF Over Time(Baseline through End of Study (EOS), Day 253)
- Change from Baseline in Cell Count in CSF Over Time(Baseline through End of Study (EOS), Day 253)
- Change from Baseline in Total Protein in Cerebral Spinal Fluid (CSF) Over Time(Baseline through End of Study (EOS), Day 253)
- Pharmacokinetics (PK) of ARO-ATXN2: Maximum Observed Plasma Concentration (Cmax)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Time to Maximum Observed Plasma Concentration (Tmax)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to 24 Hours (AUC0-24)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to the Last Quatifiable Plasma Concentration (AUClast)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Area Under the Plasma Concentration Versus Time Curve from Zero to Infinity (AUCinf)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Elimination Half-life (t1/2)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Apparent Systemic Clearance (CL/F)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Recovery of Unchanged Drug Excreted in Urine (Ae)(Through 24 hours post-dose)
- PK of ARO-ATXN2: Renal Clearance (CLr)(Through 24 hours post-dose)
- Percentage of Administered Drug Recovered in Urine(Through 24 hours post-dose)
研究者
研究点 (16)
Loading locations...
相似试验
已完成
2 期
Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3Spinocerebellar Ataxia Type 3NCT00992771University of South Florida20
终止
2 期
Acetazolamide Efficacy in Ataxia in PMM2-CDGPmm2-CDGCDG1ANCT04679389Mayo Clinic25
撤回
2 期
Trial of Oral SNC-102 in Subjects With Combat-Related Posttraumatic Stress DisorderPost-Traumatic Stress DisordersPosttraumatic Stress DisordersStress Disorders, Post-TraumaticPost-Traumatic Stress Disorders, Combat-relatedNCT02384369Synchroneuron Inc.
终止
2 期
A Phase 2a Dose Escalation Study With SLV334 in Patients With Traumatic Brain Injury.Traumatic Brain InjuryNCT00735085Abbott Products57
招募中
不适用
Spinocerebellar Ataxia Type 27B Natural History Study (SCA27B-NHS)Spinocerebellar Ataxia Type 27BNCT06472557University Hospital Tuebingen300