A Multi-center, North American, Randomized, Double-blind, Parallel Group Study Comparing Three Doses of ACR16 Versus Placebo for the Symptomatic Treatment of Huntington Disease (HART)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 227
- 试验地点
- 28
- 主要终点
- Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12
研究概览
简要总结
The purpose of this study is to determine if ACR16 is effective and safe in the symptomatic treatment of Huntington's Disease.
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
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide written Informed Consent prior to any study related procedure, including consent to genotyping of the CYP2D6 gene.
- •Clinical features of HD, and a positive family history and/or the presence of ≥ 36 CAG repeats in the Huntington gene.
- •Male or female age ≥ 30 years.
- •Willing and able to take oral medication and to comply with the study specific procedures.
- •Ambulatory, being able to travel to the assessment center, and judged by the Investigator as likely to be able to continue to travel for the duration of the study.
- •Availability of a caregiver or family member to accompany the participant to two visits.
- •A sum of ≥ 10 points on the mMS at the screening visit.
- •For participants taking allowed antidepressants or other psychotropic medication , the dosing of medication must have been kept constant for at least 6 weeks before baseline visit.
排除标准
- •Treatment with any antipsychotic medication (neuroleptics) within 8 weeks of baseline visit, or at any time point during the study period.
- •Use of tetrabenazine within 12 weeks of baseline visit, or at any time during the study period.
- •Treatment with any investigational product within 4 weeks of baseline visit.
- •Use of tricyclic antidepressants or class I antiarrhythmics within 6 weeks of baseline visit, or at any time during the study period.
- •Use of concomitant medication that may lower the seizure threshold within 6 weeks of baseline visit, or at any time during the study period .
- •Use of metoclopramide within 12 weeks of baseline visit, or at any time during the study period.
- •Participants currently receiving deep brain stimulation (DBS).
- •Participants with a history of surgical procedures aiming to improve the symptoms of Huntington disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents or previous attempts of deep brain stimulation.
- •Participants previously randomized into this study.
- •A prolonged QTc interval at Screening Visit (defined as a QTc interval of > 450 milliseconds [msec] for males or > 470 msec for females), or other clinically significant heart conditions as judged by the investigator.
- •Creatinine clearance <40 milliliters (mL)/minute (min) as measured at the screening visit.
- •Any clinically significant, abnormal, baseline laboratory result which in the opinion of the Investigator, affects the participant' suitability for the study or puts the participant at risk if he/she enters the study.
- •Clinically significant hepatic or renal impairment.
- •Participants with a known history of epilepsy or a history of febrile seizure(s) or seizure(s) of unknown cause.
- •Severe intercurrent illness, which, in the opinion of the Investigator, may put the participant at risk when participating in the trial or may influence the results of the trial or affect the subjects' ability to take part in the trial.
- •Alcohol and/or drug abuse as defined by Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM IV-TR) criteria for Substance Abuse - this includes the illicit use of cannabis within the last 12 months prior to Screening Visit
- •Participants with suicidal ideation as defined as a positive score on criteria for major depressive episode, item A9 on the DSM -IV-TR criteria for a Major Depressive Episode
- •Females who are pregnant or lactating or who intend to become pregnant during the study period.
- •Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. (Females of childbearing potential taking acceptable contraceptive precautions can be included)
- •Known allergy to any ingredients of the trial medication or placebo
- •Any previous participation in a clinical study with ACR16.
研究组 & 干预措施
Placebo
Participants will receive a placebo capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), placebo capsule will be taken twice daily (BID) as 2 separate doses.
干预措施: Placebo (Other)
ACR16 10 mg BID
Participants will receive ACR16 10 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 10 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 20 mg).
干预措施: ACR16 (Drug)
ACR16 22.5 mg BID
Participants will receive ACR16 22.5 mg capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 22.5 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 45 mg).
干预措施: ACR16 (Drug)
ACR16 45 mg BID
Participants will receive ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 12), ACR16 45 mg capsule will be taken twice daily (BID) as 2 separate doses (total dose: 90 mg).
干预措施: ACR16 (Drug)
结局指标
主要结局
Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the UHDRS Motor Assessments) at Week 12
时间窗: Baseline, Week 12
The mMS is a subscale of the UHDRS total motor score and comprises 13 responses from the 10 items, 4-10 and 13-15, from the UHDRS motor assessment. The items for mMS included dysarthria, tongue protrusion, finger taps (right and left), pronate/supinate hands (right and left), luria - first-hand-palm sequencing, arms rigidity (right and left), body bradykinesia, gait, tandem walking, and retropulsion pull test. Each of these items were rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranged from 0 to 52, with higher scores indicating more severe motor impairment. The last observation carried forward (LOCF) method was used to generate an mMS score for each participant for Week 12 assessment.
次要结局
- Change From Baseline in Total Motor Score (TMS)(Basline, Week 12)
- Number of Participants in Each of the Ratings of the Clinical Global Impression of Change (CGI-C) Scale(Week 12)
- Change From Baseline in Stroop Word Reading Test(Baseline, Week 12)
- Change From Baseline in Total UHDRS Behavioral Assessment Score(Baseline, Week 12)
- Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score(Baseline, Week 12)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Week 14)