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Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: Intramuscular Study (Allo-IM)

Primary Purpose

Alzheimer Dementia

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Allopregnanolone
Sponsored by
University of Arizona
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer Dementia focused on measuring Alzheimer's disease, Mild cognitive impairment, Dementia, Regenerative therapeutic, Drug development

Eligibility Criteria

55 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Provision of signed and dated informed consent form
  • Stated willingness to comply with all study procedures and availability for the duration of the study
  • Men or postmenopausal women, aged 55 years or older
  • Diagnosis of MCI due to AD or mild AD
  • In good general health as evidenced by medical history and with no medical contraindications to participation
  • MMSE > 20 at screen
  • Caregiver willing and capable to accompany the patient to clinic visits

Exclusion Criteria:

  • Daily 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 obtained at screening visit.
  • MRI indicative of significant abnormality, including but not limited to evidence of a single prior hemorrhage or infarct >1 cm3, multiple lacunar infarcts (>1) or evidence of a single prior infarct >1cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (e.g. abscess or tumor).
  • Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI.
  • Is currently enrolled in a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research or observational study judged not to be scientifically or medically compatible with this study.

Sites / Locations

  • University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allo IM cohort

Arm Description

Allopregnanolone 4-18mg IM, weekly, for 12 weeks.

Outcomes

Primary Outcome Measures

Safety - Adverse events
Incidence and severity of treatment emergent adverse events assessed weekly.
Safety - clinical laboratory measures
Proportion of subjects exceeding pre-established critical laboratory values.
Safety - clinical assessment
Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms.

Secondary Outcome Measures

Pharmacokinetic parameter - Cmax
Determine maximum serum concentration of Allo after IM administration of each dose.
Pharmacokinetic parameter - AUC
Determine the area under the curve after each IM administration of Allo.
Pharmacokinetic parameter - Tmax
Determine the time at which Cmax is attained.
Pharmacokinetic parameter - Clearance
Pharmacokinetic measurement of the volume of plasma from which Allo is completely removed per unit time.
Pharmacokinetic parameter - Volume of distribution
Determine the volume of distribution at steady state of Allo.
Satisfaction and feasibility of home nurse survey
Standardized patient satisfaction questionnaire to assess the feasibility of home-health care visits to administer the study medication and its desirability by participants and caregivers. Levels of satisfaction measured on a 5-point scale (1 = lowest satisfaction, 5 = greatest).

Full Information

First Posted
October 12, 2018
Last Updated
April 22, 2023
Sponsor
University of Arizona
Collaborators
University of Southern California, Alzheimer's Association
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1. Study Identification

Unique Protocol Identification Number
NCT03748303
Brief Title
Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: Intramuscular Study
Acronym
Allo-IM
Official Title
Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: IV to IM Bridging Study
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 1, 2019 (Actual)
Primary Completion Date
December 1, 2022 (Actual)
Study Completion Date
June 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Arizona
Collaborators
University of Southern California, Alzheimer's Association

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to identifying the intramuscular dose equivalent to the 4mg intravenous dose and assess its safety and tolerability as a weekly injection.
Detailed Description
The purpose of this bridging study is to advance the therapeutic development of Allopregnanolone (Allo) by using the intramuscular (IM) route of administration as an alternative to the intravenous (IV) route. In order to identify the equivalent IM dose we will conduct pharmacokinetic (PK) analysis previously informed by simulations and modeling. We will recruit a total of 12 participants, both males and females equally distributed, into this single-arm, open-label study. PK analysis and dose finding will take place for the initial 4 weeks; some participants may not require all 4 weeks of initial dosing to establish maintenance dose. Once maintenance dose is established all participants will receive weekly administration of Allo IM until they complete 12 weeks total of Allo exposure (5 or 6 clinic visits and 6 or 7 home-nurse visits).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer Dementia
Keywords
Alzheimer's disease, Mild cognitive impairment, Dementia, Regenerative therapeutic, Drug development

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Single-arm, open-label study
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Allo IM cohort
Arm Type
Experimental
Arm Description
Allopregnanolone 4-18mg IM, weekly, for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Allopregnanolone
Other Intervention Name(s)
Allo
Intervention Description
Administration of weekly IM injections of Allopregnanolone.
Primary Outcome Measure Information:
Title
Safety - Adverse events
Description
Incidence and severity of treatment emergent adverse events assessed weekly.
Time Frame
From baseline to visit 16 (14 weeks)
Title
Safety - clinical laboratory measures
Description
Proportion of subjects exceeding pre-established critical laboratory values.
Time Frame
From Baseline to visit 16 (14 weeks)
Title
Safety - clinical assessment
Description
Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms.
Time Frame
From Baseline to visit 16 (14 weeks)
Secondary Outcome Measure Information:
Title
Pharmacokinetic parameter - Cmax
Description
Determine maximum serum concentration of Allo after IM administration of each dose.
Time Frame
Visits 3 - 6 (up to 4 weeks)
Title
Pharmacokinetic parameter - AUC
Description
Determine the area under the curve after each IM administration of Allo.
Time Frame
Visits 3 - 6 (up to 4 weeks)
Title
Pharmacokinetic parameter - Tmax
Description
Determine the time at which Cmax is attained.
Time Frame
Visits 3 - 6 (up to 4 weeks)
Title
Pharmacokinetic parameter - Clearance
Description
Pharmacokinetic measurement of the volume of plasma from which Allo is completely removed per unit time.
Time Frame
Visits 3 - 6 (up to 4 weeks)
Title
Pharmacokinetic parameter - Volume of distribution
Description
Determine the volume of distribution at steady state of Allo.
Time Frame
Visits 3 - 6 (up to 4 weeks)
Title
Satisfaction and feasibility of home nurse survey
Description
Standardized patient satisfaction questionnaire to assess the feasibility of home-health care visits to administer the study medication and its desirability by participants and caregivers. Levels of satisfaction measured on a 5-point scale (1 = lowest satisfaction, 5 = greatest).
Time Frame
Visits 8-9 and 11-15 (up to 8 weeks)
Other Pre-specified Outcome Measures:
Title
MRI brain volumes
Description
To evaluate MRI-based brain volumes 1-week before before and 1-week after the administration of Allo IM for 12 weeks (total assessment period of 14 weeks).
Time Frame
Baseline to visit 16 (14 weeks)
Title
Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL)
Description
Test to evaluate changes in cognition
Time Frame
Baseline to visit 16 (14 weeks)
Title
Mini-Mental State Exam (MMSE)
Description
Test to evaluate changes in cognition.
Time Frame
Baseline to visit 16 (14 weeks)
Title
Alzheimer's Disease Assessment Scale Cognitive Subscale 14 (ADAS-Cog14)
Description
Well known test to evaluate changes in cognition. Scores on this 14 item test range from 0 (best) to 85 (worse); a positive change indicates cognitive worsening.
Time Frame
Baseline to visit 16 (14 weeks)
Title
Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
Description
Clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively).
Time Frame
Baseline to visit 16 (14 weeks)
Title
Cogstate Alzheimer's battery
Description
Test to evaluate changes in cognition.
Time Frame
Baseline to visit 16 (14 weeks)
Title
Activities of daily living
Description
To assess activities of daily living per the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-iADLS). In a structured interview format, informants are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. Scores range from 0-56.
Time Frame
Baseline to visit 16 (14 weeks)
Title
Caregiver burden survey
Description
Assessed per Zarit's burden 22-item questionnaire. Burden measured on a 5-point scale (0 = never burdened, 4 = nearly always burdened). Max score = 88
Time Frame
Baseline to visit 16 (14 weeks)
Title
Actigraphy sleep assessment - Total sleep time
Description
To assess standard sleep parameters using wearable devices (actigraph wristwatch): Total sleep time reported as time in minutes.
Time Frame
Screen to visit 16 (16 weeks)
Title
Actigraphy sleep assessment - Wake after sleep onset
Description
To assess standard sleep parameters using wearable devices (actigraph wristwatch): Wake after sleep onset (WASO) reported as time in minutes.
Time Frame
Screen to visit 16 (16 weeks)
Title
Actigraphy sleep assessment - Sleep efficiency
Description
To assess standard sleep parameters using wearable devices (actigraph wristwatch): Sleep efficiency reported as percentage.
Time Frame
Screen to visit 16 (16 weeks)
Title
Physical activity
Description
To assess daily activity using wearable devices: FitBit.
Time Frame
Screen to visit 16 (16 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Men or postmenopausal women, aged 55 years or older Diagnosis of MCI due to AD or mild AD In good general health as evidenced by medical history and with no medical contraindications to participation MMSE > 20 at screen Caregiver willing and capable to accompany the patient to clinic visits Exclusion Criteria: Daily 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 obtained at screening visit. MRI indicative of significant abnormality, including but not limited to evidence of a single prior hemorrhage or infarct >1 cm3, multiple lacunar infarcts (>1) or evidence of a single prior infarct >1cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (e.g. abscess or tumor). Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI. Is currently enrolled in a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research or observational study judged not to be scientifically or medically compatible with this study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Roberta D Brinton, PhD
Organizational Affiliation
University of Arizona
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Lon S Schneider, MD, MS
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: Intramuscular Study

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