Phase 1b, Multi-center, Randomized, Double-Blind, Placebo-Controlled, Study to Evaluate the Safety, Tolerability, PD and PK of VK0214, in Subjects With the Adrenomyeloneuropathy Form (AMN) of X-linked Adrenoleukodystrophy (X-ALD)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 9
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious AEs (TESAEs)
研究概览
简要总结
Subjects will be administered multiple doses of VK0214 in a cohort dose escalation process. A total of up to 36 subjects will be enrolled in the study, into one of three dose cohorts. For each cohort, up to 12 subjects will be randomized to receive VK0214 or placebo in a 3:1 ratio so that there will be a total of up to 9 subjects for each of the active doses and up to 3 subjects dosed with placebo in each cohort.
详细描述
The first part of VK0214-102 will include the first 2 dose cohorts and placebo, which will be dosed in parallel (up to N=24). The first 2 doses used in these cohorts will be 20 mg QD and 40 mg QD for 28 days. A Dose Level Review Team (DLRT) meeting will be held at the end of the first 2 parallel doses.
The DLRT will review safety, tolerability, and preliminary efficacy data from cohort 1 and 2. If the data analyzed show that the first 2 doses are safe and well tolerated the DLRT may make a recommendation for proceeding to commence dosing in the third dose cohort.
Based upon outcomes in Cohorts 1 and 2, the sponsor may decide to include a third dose cohort. Before screening may be initiated in Cohort 3, data to support dosing in this cohort will be submitted to the FDA, together with the amended protocol and the dosing recommendation of the DLRT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study and is willing and able to participate.
- •Have diagnosis of X-linked adrenoleukodystrophy (X-ALD) by genetic testing and elevated VLCFAs.
- •Present clinical features of AMN, or adrenal insufficiency.
- •Subjects must be 18 years of age and older.
排除标准
- •Have the cerebral form of X-ALD, based on medical records, or based on MRI performed within the last 12 months or MRI at screening
- •Have been treated with any drug targeting TRβ or with any drug being tested as therapy for X-ALD AMN form within the past 30 days before screening
- •History or presence of clinically significant acute or unstable hepatic, renal, gastrointestinal, pulmonary, immunological, endocrine, diabetes, hematological or oncological that in the opinion of the investigator would pose a significant risk for the subject
- •Subject has untreated primary adrenal insufficiency based on morning plasma cortisol and ACTH at screening
- •Lorenzo's Oil. Currently taking Lorenzo's Oil or erucic acid containing product, or other lipid lowering agent known to effect VLCFA levels
研究组 & 干预措施
VK0214 Active 20mg
20mg QD
干预措施: VK0214 (Drug)
VK0214 Active 40mg
40mg QD
干预措施: VK0214 (Drug)
Placebo
Placebo QD
干预措施: Placebo (Other)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious AEs (TESAEs)
时间窗: 28 days
Evaluate the safety and tolerability of multiple oral doses of VK0214 in subjects with AMN
次要结局
- Evaluate the Pharmacokinetics of VK0214(28 days)