Allopregnanolone Regenerative Therapeutic for Mild Alzheimer's Disease (REGEN-BRAIN©)

University of Arizona

Status and phase: Enrolling; Phase 2

Conditions: Alzheimer Dementia; Late Onset Alzheimer Disease; Neurodegenerative Diseases

Treatments: Other: Placebo; Drug: Allopregnanolone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04838301

Allo-20-001

R01AG063826 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 estimated patients

Sex: All

Ages: 55 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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200 participants in 2 patient groups, including a placebo group

Allo group

Experimental group

Description:

Allopregnanolone 4mg IV 30-minute infusion once per week for 12 months.

Treatment:

Drug: Allopregnanolone

Control group

Placebo Comparator group

Description:

Placebo (normal saline) IV 30-minute infusion once per week for 12 months.

Treatment:

Other: Placebo