A Multicentre, Multinational, Randomised, Double-Blind, Parallel-Group Study Comparing ACR16 45 mg Once-Daily or Twice-Daily Versus Placebo for the Symptomatic Treatment of Huntington's Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 437
- 试验地点
- 31
- 主要终点
- Change From Baseline in Modified Motor Score (mMS) (Sum of Score of Items 4-10 and 13-15 of the Unified Huntington's Disease Rating Scale [UHDRS] Motor Assessments) at Week 26
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.
详细描述
The primary objective in the present study is to confirm whether ACR16 is efficacious in improving voluntary motor function in Huntington's disease based on the Unified Huntington"s Disease Rating Scale (UHDRS) subscale. These symptoms seem to be most important for the functional disability associated with the disorder. To achieve this, participants are randomized to ACR16 45 mg once daily, ACR16 45 mg twice daily, or placebo treatment in equal proportions in a parallel design for a treatment duration of 26 weeks.
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.
- •Huntington's disease diagnosed with the aid of clinical features 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 able to comply with the study specific procedures.
- •Ambulatory, being able to travel to the assessment centre, 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.
- •A sum of ≥ 10 points on the mMS at the screening visit.
- •For participants taking allowed antipsychotic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomization. The allowed antipsychotic medication is Amisulpride, Haloperidol, Olanzapine, Risperidone, Sulpiride, or Tiapride.
- •For participants taking allowed antidepressant or other psychotropic medication, the dosing of medication must have been kept constant for at least 6 weeks before randomization.
- •Willing to provide a blood sample for CAG analysis (where CAG result is not already available).
- •In France only, the participant must be affiliated to a social security system or be a beneficiary of such a system.
排除标准
- •Unable to give written informed consent.
- •Treatment with any non-allowed antipsychotic medication within 12 weeks of randomization. The non-allowed antipsychotic medication is any medication other than Amisulpride, Haloperidol, Olanzapine, Risperidone, Sulpiride, or Tiapride.
- •Treatment with the antidepressants Fluoxetine or Paroxetine within 6 weeks of randomization.
- •Use of Tetrabenazine within 12 weeks of randomization, or at any time during the study period.
- •Treatment with any investigational product within 4 weeks of randomization.
- •Use of tricyclic antidepressants, class I antiarrhythmics, and strong CYP2D6 inhibitors such as Ajmalicine, Chinidin/Quinidine and Ritonavir, within 6 weeks of randomization.
- •Participants previously included into this study.
- •A prolonged QTc interval at screen (defined as a QTc interval of > 450 milliseconds [msec] for males or > 470 msec for females), or other clinically significant heart conditions.
- •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 participants' 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 history of epilepsy or a history of 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 participants' ability to take part in the trial.
- •Alcohol and/or drug abuse as defined by Diagnostic and Statistical Manual - Fourth Edition - Text Revision (DSM IV-TR) criteria for substance abuse - this includes the illicit use of cannabis within the last 12 months.
- •Participants with suicidal ideation, 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.
- •Females who are of child bearing potential and not taking adequate contraceptive precautions are excluded from the trial. Females of child bearing 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 ACR
- •Participants currently receiving deep brain stimulation.
- •Participants with a history of surgical procedures aiming to improve the symptoms of Huntington's disease, such as neural transplantations, lesions of the central nervous system, infusions of neurotrophic agents or previous attempts of deep brain stimulation.
研究组 & 干预措施
Placebo
Participants will receive a placebo capsule matching to ACR16 once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), placebo capsule will be taken twice daily as 2 separate doses.
干预措施: Placebo (Drug)
ACR16 45 mg
Participants will receive ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule will be taken as 2 separate doses.
干预措施: ACR16 (Drug)
ACR16 45 mg
Participants will receive ACR16 45 milligrams (mg) capsule orally once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), one ACR16 45 mg capsule and one placebo capsule will be taken as 2 separate doses.
干预措施: Placebo (Drug)
ACR16 90 mg
Participants will receive ACR16 45 mg capsule once daily for the first 4 weeks. After 4 weeks (Weeks 5 to 26), ACR16 45 mg capsule will be taken twice daily 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 Unified Huntington's Disease Rating Scale [UHDRS] Motor Assessments) at Week 26
时间窗: Baseline, Week 26
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 include 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 are rated on a scale of 0 (normal) to 4 (marked impairment). Total score ranges from 0 to 52, with higher scores indicating more severe motor impairment.
次要结局
- The UHDRS Functional Assessment at Week 26(Week 26)
- Number of Participants With Clinical Global Impression - Improvement (CGI-I) Score(Week 26)
- Change From Baseline in Stroop Word Reading Test at Week 26(Baseline, Week 26)
- Randomized Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to Week 30)
- Open-label Phase: Number of Participants With TEAEs(Week 26 up to Week 56)
- Change From Baseline in Total UHDRS Behavioral Assessment Score at Week 26(Baseline, Week 26)
- Change From Baseline in Total Hospital Anxiety and Depression Scale (HADS) Score at Week 26(Baseline, Week 26)