Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

Safety and Efficacy of Allopregnanolone (Allo) as a Regenerative Therapeutic for Alzheimer's Disease: Multicenter, Double-Blind, Randomized, Placebo-Controlled, Phase 2 Clinical Trial

A phase 2, double-blind, randomized, placebo-controlled clinical trial to evaluate the safety and efficacy of Allopregnanolone as a regenerative therapeutic for Alzheimer's disease.

This is a proof-of-concept phase 2 clinical trial to investigate the long-term safety and efficacy of Allo to function as a regenerative therapeutic to restore structural integrity and cognitive function of the brain in participants with mild Alzheimer's disease (AD) dementia. Study participants will be male and female, diagnosed with probable AD, Mini-Mental State Exam (MMSE) 20 to 26, ages 55 to 80 years old.

After a 2-4-week screening period, participants will be randomized to 4 mg Allo (administered intravenously over 30 minutes, once per week, in clinic) or matching placebo, 1:1 allocation, for a period of 6 months. After 6 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (3 month open-label phase). Brain imaging to evaluate the primary endpoint will be conducted at baseline, 3 and 6 months.

Main Inclusion Criteria:

• Men and postmenopausal women
• Age 55 to 80 years old
• Meets NIA-AA criteria for probable AD dementia
• MMSE of 20-26
• Plasma p-Tau217 positive
• Geriatric Depression Scale short form (GDS-S) score of ≤ 6
• No medical contraindications to participation
• Capacity to provide informed consent at screening

Main Exclusion Criteria:

• Dementia other than probable AD
• Use of benzodiazepines, anticonvulsants, antipsychotics, or other drugs that might interact with the GABA-A receptor complex
• History of stroke with a modified Hachinski Ischemic Scale score >4
• History of seizure disorder, focal brain lesion, traumatic brain injury
• History within the last 5 years of a primary or recurrent malignant disease
• Unstable or clinically significant cardiovascular, kidney or liver disease
• MRI indicative of any other significant abnormality, including but not limited to one or more significant ARIA-E or macro-hemorrhage findings, or multiple microhemorrhages (>8), or Fazekas score of 3; encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
• Any conditions that would contraindicate MRI studies.
• No evidence of AD-like pattern of brain atrophy