2023-509835-26-00已完成2 期
A Phase 2a, Randomized, Placebo-controlled, Dose-Ranging Study to Evaluate the Safety and Efficacy of PTC518 in Subjects with Huntington’s Disease
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 121
- 试验地点
- 15
- 主要终点
- Safety Endpoints: Safety profile as characterized by treatment-emergent adverse events (TEAEs), laboratory abnormalities, [CCI], electrocardiogram (ECG), vital signs, [CCI], [CCI], Columbia Suicide Severity Rating Scale (C SSRS), and physical examination
研究概览
简要总结
• Evaluate the safety of PTC518 compared with placebo in subjects with Huntington’s disease (HD) • Evaluate the pharmacodynamic (PD) effects of PTC518 through the reduction in blood total huntingtin (tHTT) protein levels
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Mild Stage 3 group
- 盲法
- Double (Subject, Investigator, Monitor, Carer)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Ambulatory male or female patient aged 25 years and older, inclusive
- •Subject is willing and able to provide informed consent and comply with all protocol requirements.
- •Genetically confirmed HD diagnosis with a cytosine-adenine-guanine (CAG) repeat length from 40 to 50, inclusive. CAG repeat length may be determined analytically through amplification.
- •Eligibility for HD-ISS Stage 2 Group (Parts A, B, and C):
- •A UHDRS IS score of 100
- •A UHDRS TFC score of 13
- •A score between 0.18 and 4.93 inclusive on the normed version of the HD prognostic index (PINHD)
- •Women of childbearing potential (WOCBP) must agree to use highly effective methods of contraception during dosing and for 6 months after stopping the study medication. Women of childbearing potential are defined as women who are fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Female partners of enrolled males who are of childbearing potential should consider use of highly effective methods of contraception while the enrolled male is taking study drug and for 6 months after stopping study drug.
- •Sexually active and fertile males must agree to use a condom during intercourse while taking study drug and for 6 months after stopping study drug and should neither father a child nor donate sperm in this period. A condom is required to be used also by vasectomized men in order to prevent potential delivery of the drug via seminal fluid.
- •Eligibility for HD-ISS Mild Stage 3 Group (Parts D, E, and F):
- •A UHDRS TFC score of 11 or 12, or a UHDRS TFC score of 13 with an UHDRS IS score of <100
排除标准
- •Inability or unwillingness to swallow oral tablets
- •Risk of a major depressive episode, psychosis, confusional state, or violent behavior as assessed by the investigator
- •Any medical history of brain or spinal disease that would interfere with the lumbar puncture processor safety assessments
- •History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
- •Any medical history or condition that would interfere with the ability to complete the protocol-specified assessments (eg, implanted shunt, conditions precluding MRI scans)
- •Antidepressant, antipsychotic, or benzodiazepine use, unless receiving a stable dose for at least 6 weeks prior to Screening and with a dose regimen that is not anticipated to change during the study. Benzodiazepine use for sedation for study-related procedures during the course of the study is permitted.
- •History of illicit/illegal drug use, or alcohol use in the high risk category of risk drinking levels according to the World Health Organization for a duration of 1 month or longer that in the opinion of the investigator could compromise the interpretability of study results
- •Clinically significant medical condition, which in the opinion of the investigator could adversely affect the safety of the subject or impair the assessment of study results (eg, inability to fast or any known hypersensitivity to PTC518 or its excipients)
- •Current significant renal impairment defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 at Screening
- •Current hepatic impairment resulting in elevated liver function tests (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP]) at 3 times the upper limit of normal at Screening
- •Pregnancy, planning on becoming pregnant during the course of the study or within 6 months of end of treatment, or currently breastfeeding
- •Receipt of an experimental agent within 90 days or 5 half-lives prior to Screening or anytime over the duration of this study, including RNA- or DNA-targeted HD-specific investigational agents (such as antisense oligonucleotides), cell transplantation, or any other experimental brain surgery
- •Use of medications that are moderate or strong inhibitors of cytochrome P450 (CYP) 3A4 within 1 week of Screening or medications that are moderate or strong inducers of CYP3A4 within 2 weeks of Screening or planned use of moderate or strong CYP3A4 inhibitor or inducer medications during the study period
- •A diagnosis of Juvenile-Onset Huntington’s Disease
- •Any history of gene therapy exposure for the treatment of HD
- •Participation in an investigational study or investigational paradigm (such as exercise/physical activity, cognitive therapy, brain stimulation, etc) within 90 days prior to Screening or anytime over the duration of this study. Observational studies (such as ENROLL-HD) are not exclusionary.
- •Presence of an implanted deep brain stimulation device
- •Brain and spinal pathology that may interfere with CSF homeostasis and circulation, increased intracranial pressure (including presence of a shunt for the drainage of CSF or an implanted central nervous system catheter catheter), malformations, and/or tumors
- •Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
- •At significant risk of suicide as measured by the C-SSRS Baseline version with a moderate risk rating or higher score
结局指标
主要结局
Safety Endpoints: Safety profile as characterized by treatment-emergent adverse events (TEAEs), laboratory abnormalities, [CCI], electrocardiogram (ECG), vital signs, [CCI], [CCI], Columbia Suicide Severity Rating Scale (C SSRS), and physical examination
Safety Endpoints: Safety profile as characterized by treatment-emergent adverse events (TEAEs), laboratory abnormalities, [CCI], electrocardiogram (ECG), vital signs, [CCI], [CCI], Columbia Suicide Severity Rating Scale (C SSRS), and physical examination
Primary Efficacy Endpoint: Change from Baseline in blood tHTT protein at Month 3
Primary Efficacy Endpoint: Change from Baseline in blood tHTT protein at Month 3
次要结局
- Change from Baseline in caudate volume as assessed via vMRI at Month 12 (key secondary)
- Change from Baseline in cUHDRS scores at Month 12
- Change from Baseline in blood tHTT protein at Month 12
- Change from Baseline in CSF mHTT protein at Month 12
- Change from Baseline in blood mHTT protein at Month 12
研究者
Allison Fortenberry
Scientific
PTC Therapeutics Inc.
研究点 (15)
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