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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04838301
Other study ID # Allo-20-001
Secondary ID R01AG063826
Status Recruiting
Phase Phase 2
First received
Last updated
Start date August 15, 2023
Est. completion date December 2026

Study information

Verified date August 2023
Source University of Arizona
Contact Claudia M Lopez, BS
Phone 520-626-6276
Email claudiml@arizona.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 200
Est. completion date December 2026
Est. primary completion date April 2025
Accepts healthy volunteers No
Gender All
Age group 55 Years to 80 Years
Eligibility 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 e4 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


Intervention

Drug:
Allopregnanolone
Allopregnanolone 4mg IV via 30-minute infusion, once per week.
Other:
Placebo
Normal saline solution IV via 30-minute infusion, once per week

Locations

Country Name City State
United States Optimus U Corporation Miami Florida

Sponsors (5)

Lead Sponsor Collaborator
University of Arizona ADM Diagnostics, Inc., National Institute on Aging (NIA), Syneos Health, University of Southern California

Country where clinical trial is conducted

United States, 

References & Publications (3)

Brinton RD, Wang JM. Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res. 2006 Jul;3(3):185-90. doi: 10.2174/156720506777632817. — View Citation

Brinton RD. Neurosteroids as regenerative agents in the brain: therapeutic implications. Nat Rev Endocrinol. 2013 Apr;9(4):241-50. doi: 10.1038/nrendo.2013.31. Epub 2013 Feb 26. — View Citation

Hernandez GD, Solinsky CM, Mack WJ, Kono N, Rodgers KE, Wu CY, Mollo AR, Lopez CM, Pawluczyk S, Bauer G, Matthews D, Shi Y, Law M, Rogawski MA, Schneider LS, Brinton RD. Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial. Alzheimers Dement (N Y). 2020 Dec 16;6(1):e12107. doi: 10.1002/trc2.12107. eCollection 2020. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Other Other regional brain volumes Change in regional brain volumes (mm3) Baseline to 12 and 18 months
Other Diffusion tensor imaging (DTI) Change in white matter tract diffusion (scalar values and/or mm2/sec) Baseline to 12 and 18 months
Other Resting state functional MRI Change in functional connectivity (z transformed correlations) Baseline to 12 and 18 months
Other Arterial spin labeling (ASL) Change in regional cerebral blood flow (mL/100g) Baseline to 12 and 18 months
Other Exploratory blood based biomarkers Change from baseline in biomarkers of AD pathology, neurogenesis and inflammation Baseline to 12 and 18 months
Other Clinical Dementia Rating (CDR) Sum of boxes score (CDR-SB): range 0-18 Baseline to 12 and 18 months
Other Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 14 Total score (range 0-90) Baseline to 12 and 18 months
Other Mini Mental State Examination (MMSE) Total score (range 0-30) Baseline to 12 and 18 months
Other Neuropsychiatric Inventory-Questionnaire (NPI-Q) Total score (range 0-36). Higher scores indicate greater symptom severity Baseline to 12 and 18 months
Other EuroQol 5-Dimension / 5-Level health-related quality of life scale scores (EQ-5D-5L) Reported as frequency, percentage and index value. Baseline to 12 and 18 months
Other Quality of Life in Alzheimer's Disease scale (QoL-AD) Total score (range 13-52). Higher score indicate better QoL Baseline to 12 and 18 months
Other Zarit Burden Interview (ZBI) Total score (range 0-48). Higher scores indicate high burden Baseline to 12 and 18 months
Primary Hippocampal volume mm3 Baseline to 12 months
Secondary Cambridge Cognition's Paired Associates Learning Test Total errors score (adjusted) - number of errors made by the participant (range: 0 to ~120). Higher scores indicate poor performance. Baseline to 12 months
Secondary Cambridge Neuropsychological Test Automated Battery (CANTAB) Composite score (higher score indicate better outcome) Baseline to 12 months
Secondary Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) 11 Total score (range 0 to 70); higher scores indicate poor performance. Baseline to 12 months
Secondary Alzheimer's Disease Cooperative Study (ADCS) Instrumental Activities of Daily (iADL) Living (iADL) iADL subscore (range 0-56): Lower score indicates greater severity Baseline to 12 months
Secondary Safety and tolerability Frequency of adverse events and serious adverse events Baseline to 12 months
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