An Open-Label Adaptive Multiple-Dose Study to Investigate the Pharmacokinetics and Pharmacodynamics of RO7234292 in CSF and Plasma, and Safety and Tolerability Following Intrathecal Administration in Patients With Huntington's Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 3
- 主要终点
- Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)
研究概览
简要总结
Study BP40410 is an open-label, adaptive multiple-dose clinical study designed to characterize the PK of RO7234292 (RG6042) in plasma and CSF as well as the acute time course and recovery profile of CSF mHTT lowering in response to RO7234292 (RG6042) treatment after intrathecal (IT) administration of RO7234292 (RG6042) to patients with manifest Hungtington's disease (HD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Manifest HD diagnosis
- •Independence Scale score of >=
- •Genetically confirmed disease by direct deoxyribonucleic acid testing with a cytosine, adenine, and guanine base sequence found in DNA which is translated into glutamine (CAG) age product (CAP) score >
- •Ability to read the words "red," "blue," and "green" in the patient's native language.
- •Ability to walk unassisted without a cane or walker and move about without a wheelchair on a daily basis as reviewed at screening and baseline visit.
- •Ability to undergo and tolerate MRI scans.
排除标准
- •History of attempted suicide or suicidal ideation with plan (i.e., active suicidal ideation) that required hospital visit and/or change in level of care within 12 months prior to screening.
- •Current active psychosis, confusional state, or violent behavior.
- •Any serious medical condition or clinically significant laboratory, vital signs, or ECG abnormalities at screening that, in the Investigator's judgment, precludes the patient's safe participation in and completion of the study.
- •Clinical diagnosis of chronic migraines or history of low pressure headache after lumbar puncture requiring hospitalization or blood patch.
- •Treatment with investigational therapy within 4 weeks prior to screening or 5 drug elimination half-lives of investigational therapy, whichever is longer.
- •Concurrent or planned concurrent participation in any interventional clinical study, including explicit pharmacological and non-pharmacological interventions. Observational studies are acceptable.
- •Unable or unsafe to perform lumbar puncture on the patient.
- •Previous lumbar surgery that is likely, in the opinion of the Investigator or surgical team, to make IT catheter insertion or IT injection unduly difficult or hazardous.
- •Poor peripheral venous access.
- •Scoliosis or spinal deformity making IT injection not feasible in the outpatient setting.
- •Preexisting intra-axial or extra-axial lesions as assessed by a centrally read MRI scan during the screening period.
研究组 & 干预措施
Dose level 1 of RO7234292 (RG6042)
Participants will receive dose level 1 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
干预措施: RO7234292 (RG6042) (Drug)
Dose level 2 of RO7234292 (RG6042)
Participants will receive dose level 2 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
干预措施: RO7234292 (RG6042) (Drug)
Dose level 3 of RO7234292 (RG6042)
Participants will receive dose level 3 of RO7234292 (RG6042) intrathecally on Day 1 and Day 29.
干预措施: RO7234292 (RG6042) (Drug)
结局指标
主要结局
Concentrations of RO7234292 in CSF (Cerebrospinal Fluid)
时间窗: Day 1, 2, 3, 4, 29, 43, 71, 127, and follow-up visit (6 months after last study drug administration)
NA represents: insufficient number of participants with events.
Concentrations of RO7234292 in Plasma
时间窗: Day 1, 2, 3, 4, 5, 28, 29, 30, 43, 71, 127, and follow-up visit (6 months after last study drug administration)
NA represents:insufficient number of participants with events
mHTT (Mutant Huntingtin) Concentration in CSF
时间窗: Days 1, 2, 3, 29, 43, 71, 127 and follow-up visit (6 months after last study drug administration)
CSF Mutant Huntingtin Protein (fmol/L) values at time point visits are reported.
次要结局
- Percentage of Participants With Adverse Events According to NCI-CTCAE Grading System(Up to 6 months)
- Percentage of Participants With Suicidal Ideation or Behavior, as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score(From Screening Day Up To Follow-up Visit (6 months after the last Dosing Day-Day 127))
- Incidence of Anti-Drug Antibodies (ADAs)(Day 1, Day 28, and follow-up visit (6 months after last study drug administration))
- Titer and Antibody Subtype, Determined if ADAs Are Identified(Day 1, Day 28, and follow-up visit (6 months after last study drug administration))
- Amount of RO7234292 in Urine Ae (Micrograms)(Up to 72 hours)