An Exploratory Clinical Trial in Early Stage Huntington's Disease Patients to Assess Pharmacokinetics, Candidate Pharmacodynamic Measures of Target Engagement and Disease Modulation as Well as Acute Phenotypical Effects Following Multiple Oral Doses of SEN0014196.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 55
- 试验地点
- 1
- 主要终点
- To determine the change from baseline of a series of pharmacodynamic markers in peripheral blood mononuclear cells
研究概览
简要总结
The primary objective of this study is to provide biological samples from patients with Huntington's disease to allow characterisation of the pharmacological mechanism of action of SEN0014196.
详细描述
This study will establish the acute phenotypical and biological effects of repeated dose application of SEN0014196 in patients with Huntington's disease, providing biomaterials for biomarker studies (levels of circulating huntingtin, acetylation status of mutant huntingtin, innate immune markers, transcriptional profiles). Evaluation of phenotypic effects will include UHDRS scores, total functional capacity. Safety assessments will include ECG, vital signs, laboratory safety tests and physical examination.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with early Huntington's Disease (age: 18 to 70 years), i.e. genetically confirmed (CAG repeat length ≥36) HD, motor signs of HD (motor score of the UHDRS > 5) and a TFC of ≥
- •All patients will have a body weight greater than 50 kg.
- •Female subjects must be surgically sterile or post-menopausal, no spontaneous menstruation for at least one year before the first dose, non-lactating and have a negative urine pregnancy test. Male subjects participating in the trial and their female contraception from the time of taking the first dose of the study drug until three months after taking the last dose. This must include a condom or other barrier method.
- •All subjects must be capable of providing written informed consent.
- •Subjects must have no clinically significant and relevant history that could affect the conduct of the study and evaluation of the data, as ascertained by the Investigator through detailed medical history and screening assessments.
排除标准
- •Participation in a study of an investigational drug within 30 days of the baseline visit.
- •Subjects with presence of psychosis and/or confusional states.
- •Subjects with clinically significant laboratory or ECG abnormalities at Screening.
- •Subjects with clinically relevant hematological, hepatic, cardiac or renal disease.
- •A medical history of infection with human immunodeficiency virus, hepatitis C and/or hepatitis B.
- •Any relevant condition, behaviour, laboratory value or concomitant medication which, in the opinion of the Investigator, makes the subject unsuitable for entry into the study.
- •Subjects who have previously received histone deacetylase inhibitors e.g. vorinostat or have participated in a clinical trial using compound suspected of interfering with protein acetylation status.
- •A history of malignancy of any type within 2 years prior to screening. A history of surgically excised nonmelanoma skin cancers is permitted.
- •Subjects with a significant history of drug allergy as determined by the Investigator.
- •Subjects who have a significant history of alcoholism or drug/chemical abuse as determined by the Investigator.
研究组 & 干预措施
SEN0014196 (Low Dose)
10 mg, once daily administration (immediate release capsule)
干预措施: SEN0014196 (Low Dose) (Drug)
SEN0014196 (High dose)
100 mg, once daily administration (immediate release capsule)
干预措施: SEN0014196 (High Dose) (Drug)
Placebo
Once daily (immediate release capsule)
干预措施: Placebo (Drug)
结局指标
主要结局
To determine the change from baseline of a series of pharmacodynamic markers in peripheral blood mononuclear cells
时间窗: Baseline, Day 7, Day 14, Follow-Up
Collection of peripheral blood mononuclear cells for biomarker investigations, specifically acetylation status of mutant huntingtin, levels of circulating huntingtin, innate immune markers and transcriptional profiles
次要结局
- To determine the safety and tolerability following repeated doses of SEN0014196 over two weeks at two dose levels in patients with Huntington's disease(Baseline, Day 7, Day 14, Follow-up)
- To determine the pharmacokinetics of repeated doses of SEN0014196 at two dose levels when administered over two weeks in patients with Huntington's disease(Baseline, Day 14)