2025-525111-17-00已完成2 期
A Phase 1b/2a first-in-human, multicentre, randomized, double-blind, placebo-controlled study of multiple ascending dose (Part1) followed by an open-label extension (Part2) to assess the safety, tolerability, and pharmacokinetics of intrathecally administered S233107 in participants with spinocerebellar ataxia type 3
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 14
- 主要终点
- Part 1 and 2: - Incidence and severity of AEs - Incidence of abnormalities in 12-lead ECG, clinical laboratory assessments in blood and CSF, vital signs, weight, and suicide risk.
研究概览
简要总结
Part 1: To evaluate the safety and tolerability of multiple intrathecal (IT) administrations of S233107 in comparison with placebo IT administration in participants with spinocerebellar ataxia type 3 (SCA3).
Part 2: To evaluate the safety and tolerability of multiple IT administrations of S233107 in participants with SCA3.
研究设计
- 分配方式
- Na
- 主要目的
- Ole Part 2
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Male and female aged ≥ 18 to ≤ 65 years of age at screening visit.
- •Genetically documented diagnosis of SCA3 with Ataxin-3 (ATXN3) cytosine-adenine-guanine (CAG) repeat length on one allele of the ATXN3 gene ≥ 60 based on local testing from an accredited laboratory.
- •Participants should be ambulatory on their own, i.e., without permanent and continuous use of walking aid (ankle-foot orthosis are allowed) or reliance on a supporting arm during outside walk (adapted Klockgether stage 1). − and total Scale of the Assessment and Rating of Ataxia (SARA) ≥ 3 − and 1 ≤ SARA gait subscore ≤ 4 at screening visit.
- •Treatment naive or on a stable dose of symptomatic treatment (e.g., amantadine, buspirone, riluzole, dalfampridine, Thyrotropin-releasing hormone or TRH analogue, varenicline, valproic acid, acetazolamide, trehalose) for ataxia symptoms for a minimum of 3 months prior to baseline visit.
- •Stable non-pharmacological therapy, e.g., physical therapy, speech therapy, transcranial brain stimulation, and others, for a minimum of 3 months prior to baseline visit.
- •Determined by the investigator to be medically stable at baseline/randomization as assessed by medical history, physical examination, laboratory test results, and 12-lead electrocardiogram (ECG) testing.
排除标准
- •Any type of ataxia other than SCA3 as comorbidity (e.g., acquired or secondary to another medical condition, including but not limited to, alcoholism, head injury, multiple sclerosis, olivopontocerebellar atrophy, multiple system atrophy, or stroke).
- •Contraindications to MRI procedure.
- •History of epilepsy or the occurrence of seizures within 3 years prior to screening visit.
- •History of persistent alcohol or substance abuse, misuse or dependency of, within the last 2 years prior to screening visit.
- •Additional criteria for Part 2: The inclusion and exclusion criteria above will apply to participants in Part 1 and to each additional participant enrolled in Part
- •Additional criteria for Part 2: Participants who complete Part 1 may proceed to Part 2 if continuation in this clinical study is deemed appropriate by the investigator and provided no stopping criteria have been met.
- •Additional criteria for Part 2: Participants from Cohort 1 will need to comply with all inclusion and exclusion criteria, once entering Part 2 of the study, except for inclusion criteria linked to disease severity (i.e., Klockgether stage 1 and total SARA ≥ 3 and 1 ≤ SARA gait subscore ≤ 4).
- •Any condition that may interfere with the assessment of SCA3-related signs and symptoms (e.g., severe musculoskeletal disorders, arthritis affecting joints, or nerve injuries, etc.) in the judgment of the investigator.
- •Severe vision or hearing impairment (that is not corrected by glasses or hearing aids) that may interfere with the participant’s ability to perform study assessments (in the judgment of the investigator).
- •Prominent spasticity or dystonia that will compromise the ability of the SARA assessment to reflect underlying ataxia severity (in the judgment of the investigator).
- •CAG repeat length ≥ 60 in the ATXN3 gene in both alleles (homozygous) on documented genetic testing.
- •Age at SCA3 symptom onset < 18 years.
- •Brain Magnetic Resonance Imaging (MRI) abnormalities that could contribute to or interfere with the participant’s clinical state other than findings typical of SCA3, or any finding that might pose a risk to the participant (in the judgment of the investigator).
- •History of post-dural puncture headache of moderate or severe intensity requiring hospitalization or blood patch.
- •Contraindications for lumbar puncture (LP) and IT administration .
研究组 & 干预措施
S233107 Solution for injection 4 mg/mL, S233107 Solution for injection 15 mg/mL
Test
干预措施: S233107 Solution for injection 15 mg/mL (Drug)
S233107 Solution for injection 4 mg/mL, S233107 Solution for injection 15 mg/mL
Test
干预措施: S233107 Solution for injection 4 mg/mL (Drug)
Placebo matching S233107
Placebo
干预措施: Placebo matching S233107 (Drug)
结局指标
主要结局
Part 1 and 2: - Incidence and severity of AEs - Incidence of abnormalities in 12-lead ECG, clinical laboratory assessments in blood and CSF, vital signs, weight, and suicide risk.
Part 1 and 2: - Incidence and severity of AEs - Incidence of abnormalities in 12-lead ECG, clinical laboratory assessments in blood and CSF, vital signs, weight, and suicide risk.
次要结局
- Part 1 and 2: - Concentrations and derived PK parameters of S233107 in CSF and plasma, including but not limited to CSF Ctrough, plasma Cmax and plasma AUC0-tau.
研究者
Clinical Studies Department
Scientific
Institut De Recherches Internationales Servier IRIS
研究点 (14)
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