Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: Intramuscular Study (Allo-IM)
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|ClinicalTrials.gov Identifier: NCT03748303|
Recruitment Status : Recruiting
First Posted : November 20, 2018
Last Update Posted : January 29, 2020
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer Dementia||Drug: Allopregnanolone||Phase 1|
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).
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Single-arm, open-label study|
|Masking:||None (Open Label)|
|Official Title:||Allopregnanolone Regenerative Therapeutic for Early Alzheimer's Disease: IV to IM Bridging Study|
|Actual Study Start Date :||October 1, 2019|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||October 2020|
Experimental: Allo IM cohort
Allopregnanolone 4-18mg IM, weekly, for 12 weeks.
Administration of weekly IM injections of Allopregnanolone.
Other Name: Allo
- Safety - Adverse events [ Time Frame: From baseline to visit 16 (14 weeks) ]Incidence and severity of treatment emergent adverse events assessed weekly.
- Safety - clinical laboratory measures [ Time Frame: From Baseline to visit 16 (14 weeks) ]Proportion of subjects exceeding pre-established critical laboratory values.
- Safety - clinical assessment [ Time Frame: From Baseline to visit 16 (14 weeks) ]Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms.
- Pharmacokinetic parameter - Cmax [ Time Frame: Visits 3 - 6 (up to 4 weeks) ]Determine maximum serum concentration of Allo after IM administration of each dose.
- Pharmacokinetic parameter - AUC [ Time Frame: Visits 3 - 6 (up to 4 weeks) ]Determine the area under the curve after each IM administration of Allo.
- Pharmacokinetic parameter - Tmax [ Time Frame: Visits 3 - 6 (up to 4 weeks) ]Determine the time at which Cmax is attained.
- Pharmacokinetic parameter - Clearance [ Time Frame: Visits 3 - 6 (up to 4 weeks) ]Pharmacokinetic measurement of the volume of plasma from which Allo is completely removed per unit time.
- Pharmacokinetic parameter - Volume of distribution [ Time Frame: Visits 3 - 6 (up to 4 weeks) ]Determine the volume of distribution at steady state of Allo.
- Satisfaction and feasibility of home nurse survey [ Time Frame: Visits 8-9 and 11-15 (up to 8 weeks) ]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).
- MRI brain volumes [ Time Frame: Baseline to visit 16 (14 weeks) ]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).
- Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) [ Time Frame: Baseline to visit 16 (14 weeks) ]Test to evaluate changes in cognition
- Mini-Mental State Exam (MMSE) [ Time Frame: Baseline to visit 16 (14 weeks) ]Test to evaluate changes in cognition.
- Alzheimer's Disease Assessment Scale Cognitive Subscale 14 (ADAS-Cog14) [ Time Frame: Baseline to visit 16 (14 weeks) ]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.
- Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) [ Time Frame: Baseline to visit 16 (14 weeks) ]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).
- Cogstate Alzheimer's battery [ Time Frame: Baseline to visit 16 (14 weeks) ]Test to evaluate changes in cognition.
- Activities of daily living [ Time Frame: Baseline to visit 16 (14 weeks) ]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.
- Caregiver burden survey [ Time Frame: Baseline to visit 16 (14 weeks) ]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
- Actigraphy sleep assessment - Total sleep time [ Time Frame: Screen to visit 16 (16 weeks) ]To assess standard sleep parameters using wearable devices (actigraph wristwatch): Total sleep time reported as time in minutes.
- Actigraphy sleep assessment - Wake after sleep onset [ Time Frame: Screen to visit 16 (16 weeks) ]To assess standard sleep parameters using wearable devices (actigraph wristwatch): Wake after sleep onset (WASO) reported as time in minutes.
- Actigraphy sleep assessment - Sleep efficiency [ Time Frame: Screen to visit 16 (16 weeks) ]To assess standard sleep parameters using wearable devices (actigraph wristwatch): Sleep efficiency reported as percentage.
- Physical activity [ Time Frame: Screen to visit 16 (16 weeks) ]To assess daily activity using wearable devices: FitBit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03748303
|Contact: Gerson Hernandez, MD, MPHemail@example.com|
|Contact: Claudia M Lopez, BSfirstname.lastname@example.org|
|United States, California|
|University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II||Recruiting|
|Los Angeles, California, United States, 90033|
|Principal Investigator:||Roberta D Brinton, PhD||University of Arizona|
|Principal Investigator:||Lon S Schneider, MD, MS||University of Southern California|