Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease

Phase 2

Recruiting

• Conditions: Alzheimer Dementia; Neurodegenerative Diseases; Late Onset Alzheimer Disease
• Interventions: Drug: Allopregnanolone; Other: Placebo

• Registration Number: NCT04838301
• Lead Sponsor: University of Arizona

Brief Summary

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.

Detailed Description

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, APOE ε4 positive 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 12 months. After 12 months, all participants in the placebo group will be crossed-over to receive Allo for the remainder of the study (6 month open-label phase). Brain imaging to evaluate the primary endpoint will be conducted at baseline, 6 and 12 months.

Study Timeline

• Study First Submitted: 2021-03-25
• Study First Submitted QC: 2021-04-06
• Study First Posted: 2021-04-09
• Study Start: 2023-08-15
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-11
• Primary Completion: 2026-03
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Men and postmenopausal women
• Age 55 to 80 years old
• Meets NIA-AA criteria for probable AD dementia
• MMSE of 20-26
• APOE ε4 positive
• Geriatric Depression Scale short form (GDS-S) score of ≤ 6
• No medical contraindications to participation
• Capacity to provide informed consent at screening

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Allo group	Allopregnanolone	Allopregnanolone 4mg IV 30-minute infusion once per week for 12 months.
Control group	Placebo	Placebo (normal saline) IV 30-minute infusion once per week for 12 months.

Primary Outcome Measures

Name	Time	Method
Hippocampal volume	Baseline to 12 months	mm3

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability	Baseline to 12 months	Frequency of adverse events and serious adverse events
Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11	Baseline to 12 months	Total score (range 0 to 70); higher scores indicate poor performance.
Cambridge Cognition's Paired Associates Learning Test	Baseline to 12 months	Total errors score (adjusted) - number of errors made by the participant (range: 0 to \~120). Higher scores indicate poor performance.
Cambridge Neuropsychological Test Automated Battery (CANTAB)	Baseline to 12 months	Composite score (higher score indicate better outcome)
Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL)	Baseline to 12 months	iADL subscore (range 0-56): Lower score indicates greater severity

Trial Locations

Locations (8)

Perseverance Research Center; 🇺🇸 Scottsdale, Arizona, United States

ATP Clinical Research; 🇺🇸 Costa Mesa, California, United States

Syrentis Clinical Research; 🇺🇸 Santa Ana, California, United States

Optimus U Corporation; 🇺🇸 Miami, Florida, United States

Miami Jewish Health; 🇺🇸 Miami, Florida, United States

Combined Research; 🇺🇸 Orlando, Florida, United States

Conquest Research; 🇺🇸 Winter Park, Florida, United States

MedVadis Research; 🇺🇸 Waltham, Massachusetts, United States