A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Doses of Intrathecally Administered ISIS 443139 in Patients With Early Manifest Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 9
- 主要终点
- Number of Participants With Treatment-related Adverse Events (TEAEs)
研究概览
简要总结
This study tested the safety, tolerability, pharmacokinetics and pharmacodynamics of multiple ascending doses of ISIS 443139 administered intrathecally to adult participants with early manifest 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
- 25 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with early manifest Huntington's disease
- •Male or female, aged 25 to 65 years, inclusive, at the time of informed consent
- •Able and willing to meet all study requirements, including travel to Study Center and participation in all procedures and measurements at study visits
- •Have a trial partner who is reliable, competent and at least 18 years of age, is willing to accompany the participant to select trial visits and to be available to the Study Center by phone if needed
- •Able to tolerate MRI scans, blood draws and lumbar punctures
- •Reside within 4 hours travel of the Study Center
排除标准
- •Clinically significant medical condition, such as severe chorea, active suicidal ideation or any other conditions which would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study
- •Recent treatment with another investigational drug, biological agent, or device
- •Prior treatment with an antisense oligonucleotide [including small interfering ribonucleic acid (siRNA)]
- •Any history of gene therapy or cell transplantation or any other experimental brain surgery
- •Presence of an implanted shunt for the drainage of cerebrospinal fluid (CSF) or an implanted central nervous system (CNS) catheter
- •History of post-lumbar-puncture headache of moderate or severe intensity and/or blood patch
- •Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated
- •Hospitalization for any major medical or surgical procedure involving general anesthesia within 12 weeks of Screening or planned during the study
研究组 & 干预措施
ISIS 443139 120 mg
Participants received ISIS 443139, 120 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: ISIS 443139 120 mg (Drug)
ISIS 443139 10 mg
Participants received ISIS 443139, 10 milligrams (mg), by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: ISIS 443139 10 mg (Drug)
ISIS 443139 30 mg
Participants received ISIS 443139, 30 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: ISIS 443139 30 mg (Drug)
ISIS 443139 60 mg
Participants received ISIS 443139, 60 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: ISIS 443139 60 mg (Drug)
ISIS 443139 90 mg
Participants received ISIS 443139, 90 mg, by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: ISIS 443139 90 mg (Drug)
Placebo
Participants received placebo, by intrathecal injection, on Study Days 1, 29, 57, and 85.
干预措施: Placebo (Other)
结局指标
主要结局
Number of Participants With Treatment-related Adverse Events (TEAEs)
时间窗: Up to approximately 28 weeks
An adverse event (AE) was any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. An AE was to be regarded as a TEAE if it was present prior to receiving the first dose of Study Drug and subsequently worsened or was not present prior to receiving the first dose of Study Drug but subsequently appeared.
次要结局
- Observed Cerebrospinal Fluid (CSF) Concentration for ISIS 443139(Days 1, 29, 57, 85, and 113 or 141)