A Phase 2b/3 Study of the Safety and Efficacy of AMX0035 in Progressive Supranuclear Palsy (ORION)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 110
- 试验地点
- 62
- 主要终点
- Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
研究概览
简要总结
A35-009 (ORION) is a Phase 2b/3 trial to evaluate the efficacy and safety of AMX0035 in participants with Progressive Supranuclear Palsy (PSP), consisting of randomized, double blind placebo controlled phases, followed by an optional open-label extension phase.
详细描述
AMX0035 is a fixed dose combination therapy designed to reduce neuronal death through blockade of key cellular death pathways originating in the endoplasmic reticulum (ER) and mitochondria. This clinical trial is designed to demonstrate that AMX0035 is safe and tolerable, and to assess its effect on disease progression as measured by the Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS) over a 52-week double-blind phase. The Phase 2b and Phase 3 study portions are planned to feature an identical design: a randomized, double-blind, placebo-controlled phase that is followed by an optional open-label extension (OLE) phase. The phase 3 portion of ORION may be initiated based on results of the phase 2b Interim Analysis and/or the Primary Analysis and the totality of data from the Phase 2b study portion.
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)
盲法说明
Participants, Care providers, Investigators, and study staff will be blinded to participant group assignment during the double-blind phase and extension phase
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female 40 to 80 years of age, inclusive
- •Diagnosis of possible or probable PSP Richardson Syndrome
- •Presence of PSP symptoms for <5 years
- •Score of <40 on the total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS)
- •Able to walk independently or with minimal assistance
- •Minimum score of 24 on the Mini Mental State Examination (MMSE)
- •Must reside outside a skilled nursing facility or dementia care facility at the time of screening. Residence in an assisted living facility is allowed
- •Must have a study partner willing to attend study visits and provide information on participant's status
- •Capable of providing informed consent
- •Capable and willing to comply with trial procedures including visits to the trial clinic, visit requirements and treatment schedule, including MRI scans
- •Female participants of childbearing potential must agree to use effective birth control for the duration of the study and for 6 months after last dose of study drug.
- •Males must agree to use effective birth control method for the duration of the study and for 6 months after the last dose of study drug. Men must not plan to donate sperm.
排除标准
- •Require use of a feeding tube
- •Evidence of any neurological disorder that could explain signs of PSP
- •Evidence of any clinically significant neurological disorder other than PSP, including significant cerebrovascular abnormalities, vascular dementia, motor neuron disease or ALS, Huntington's disease, normal pressure hydrocephalus, brain tumor, seizure disorder, multiple sclerosis, or known structural brain abnormalities.
- •History of autosomal dominant PSP due to a Microtubule Associated Protein Tau (MAPT) mutation
- •History of an autosomal dominant mutation associated with Frontotemporal Lobar Degeneration (FTLD)
- •Prior or current diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder
- •Presence of unstable psychiatric disease, cognitive impairment (e.g., major cognitive dysfunction), dementia, major depression, or substance abuse that would impair ability of the participant to provide informed consent and follow instructions
- •Abnormal liver function
- •Renal insufficiency
- •Ongoing anemia
- •History of Class III/IV heart failure per New York Heart Association (NYHA)
研究组 & 干预措施
AMX0035
AMX0035 administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study
For participants electing to continue into the open-label phase at Week 52; AMX0035 will be administered once daily for first 2 weeks and then twice daily for remainder of open-label phase
干预措施: AMX0035 (Drug)
Placebo
Placebo administered by mouth for 52 weeks: once daily for first 2 weeks and then twice daily for remainder of study
干预措施: Placebo (Other)
结局指标
主要结局
Change in total (28-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score
时间窗: 52 weeks
Assess the impact of AMX0035 on disease progression as measured by the Progressive Supranuclear Palsy (PSP) Rating Scale (PSPRS); Total scores range from 0-96 with higher scores indicating more progressed disease
次要结局
- Change in total (10-item) Progressive Supranuclear Palsy Rating Scale (PSPRS) Score(52 weeks)
- Frequency of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)(52 weeks)
- Change in MDS-UPDRS Part II Score(52 weeks)