Allopregnanolone Regenerative Therapeutic for MCI/AD: Dose Finding Phase 1
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety profile: ARIA
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose.
详细描述
- Each dose group will be comprised of 8 participants (6 randomized to allopregnanolone; 2 randomized to placebo) administered one dose of allopregnanolone or placebo once per week for 12 weeks. A higher dose will be administered to the next group of participants when the lower dose is shown to be safe and tolerable. 2) Pharmacokinetic analyses will be conducted on blood samples taken from participants at the beginning and end of the trial. 3) The trial will assess safety including via MRI brain imaging.
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
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or postmenopausal women
- •55 years of age or older
- •Diagnosis of MCI due to AD or mild AD
- •MMSE > 20 at screen
- •Capacity to provide informed consent
- •Residing in the community with a caregiver able to accompany the patient to clinic visits
- •No medical contraindications to participation
- •Willingness to comply with study procedures
排除标准
- •Use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex
- •Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy
- •Clinically significant laboratory or ECG abnormality
- •MRI indicative of any other significant abnormality, including but not limited to evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
- •Any condition that would contraindicate an MRI such as the presence of metallic objects in the eyes, skin, heart, or body
研究组 & 干预措施
Placebo
Drug: Placebo injection (intravenous solution) once per week for 12 weeks
干预措施: Placebo injection (intravenous solution) (Drug)
Allopregnanolone 2 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
干预措施: Allopregnanolone injection (intravenous solution) (Drug)
Allopregnanolone 4 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
干预措施: Allopregnanolone injection (intravenous solution) (Drug)
Allopregnanolone 6-18 mg
Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks
干预措施: Allopregnanolone injection (intravenous solution) (Drug)
结局指标
主要结局
Safety profile: ARIA
时间窗: From Baseline to week 13
MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA
Safety profile: Physical and neurological examination
时间窗: From Baseline to week 16
To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.
Tolerability - Maximum tolerated dose (MTD)
时间窗: From Baseline to week 12
Onset of sedation will define the upper most limit of drug dose
Safety profile: Adverse events
时间窗: From Baseline to week 16
Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.
Safety profile: Clinical laboratory measurements
时间窗: From Baseline to week 13
Evaluating the proportion of subjects exceeding pre-established critical values per treatment arm: Alanine aminotransferase (ALT, U/L) \> 5 times upper normal limit Aspartate aminotransferase (AST, U/L) \> 5 times upper normal limit Total serum bilirubin (mg/dl) \> 2 times upper normal limit Serum creatinine (mg/dl) \> 2 times upper normal limit Serum creatine phosphokinase (U/L) \> 5 times upper normal limit
次要结局
- Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)(Weeks: 1 and 12)
- Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)(Weeks: 1 and 12)
- Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)(Weeks: 1 and 12)
- Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)(Weeks: 1 and 12)
- Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)(Weeks: 1 and 12)
- Cognitive tests (ADAS-Cog; MMSE/MoCA; ADCS-CGIC; CogState)(Baseline to Week 13)
- Brain MRI volumetrics(Baseline and Week 13)