A Randomized, Double-Blind, Placebo-Controlled; Phase 1b, Safety, Tolerability, and Pharmacokinetic Study of Multiple Ascending Doses of GC021109 in Subjects With Mild to Moderate Alzheimer's Disease
Overview
- Phase
- Phase 1
- Intervention
- GC021109
- Conditions
- Alzheimer's Disease
- Sponsor
- GliaCure, Inc.
- Enrollment
- 39
- Locations
- 5
- Primary Endpoint
- Assessment of the number and severity of treatment-emergent AEs (TEAEs) following single oral doses of GC021109 and placebo from Day 1 through Day 28
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
This is a Phase 1b, multi-center, randomized, double-blind, placebo-controlled study designed to evaluate the safety, tolerability, and pharmacokinetics of GC021109 in subjects with mild to moderate Alzheimer's Disease (as determined by 2011 National Institute on Aging- Alzheimer's Association [NIA-AA] criteria and Mini Mental State Examination [MMSE]). The Investigator, study site staff, (with exception of a designated pharmacist/pharmacy technician) and all study subjects will be blinded to randomized study medication assignment until database lock. Treatment assignments may be unblinded for select pre-authorized individuals involved in the safety and PK data reviews in order to accurately determine how to proceed with dose escalation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female subjects aged 55-85 years, inclusive, at the time of informed consent.
- •Subjects diagnosed with mild to moderate AD as determined by the following:
- •Diagnosis of probable AD according to the 2011 NIA-AA criteria
- •MMSE (using serial 7's) score of 12-26 at screening (Mild defined as 20-26 and Moderate defined as 12-19)
- •Documentation in the clinic notes of mild/moderate AD
- •If on AD therapy, stable dose for at least 3 months prior to screening.
- •All male subjects must practice effective contraception during the study. Females of childbearing potential must use a medically accepted form of birth control, unless postmenopausal for \> 1 year (as documented by elevated follicle-stimulating hormone \[FSH\]) or surgically sterile. All females of childbearing potential must have a negative serum pregnancy test (human chorionic gonadotropin beta \[hCGβ\]) at screening and a negative urine pregnancy test on Day 1 pre-dose.
- •Body mass index (BMI) between 18 and 35 kg/m2, inclusive, at screening.
- •Must have an eligible caregiver (who spends a minimum of 10 hours per week with the subject) who will be available for the duration of the study to serve as the subject's designee. Caregiver must be willing to comply with study procedures.
- •Caregiver must sign a caregiver ICF after the nature and risks of study participation have been fully explained to them.
Exclusion Criteria
- •MRI findings inconsistent with AD within the previous 12 months. All subjects must have had a MRI within the previous 12 months to be eligible.
- •History or current evidence of any clinically significant cardiac, endocrinologic, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal, or other major disease, as determined by the Investigator.
- •History of cancer within the past five years (excluding non-melanoma skin cancer).
- •Active suicidal ideation reported on the Columbia - Suicide Severity Rating Scale (C SSRS) at screening.
- •Clinically significant abnormal laboratory test values at screening (as determined by the Investigator), including:
- •any values for alanine aminotransferase (ALT) or aspartate aminotransferase (AST) that are 1.5 times above the upper limit of the reference range
- •any values for total or direct bilirubin that are 1.5 times above the upper limit of the reference range
- •estimated glomerular filtration rate \<85ml/min/1.73m
- •Subjects with a QTc of ≥450 msec for males and ≥470 msec for females at screening.
- •Participation in another clinical trial or treatment with an investigational agent within 30 days or 5 half-lives, whichever is longer, prior to Day
Arms & Interventions
Treatment Cohort 1
Each study participant will be administered with one 1mg dose capsule per day of GC021109 for 28 days.
Intervention: GC021109
Placebo Cohort 1
Patients receiving placebo as part of each cohort will be dosed with a comparable capsule to those in the treatment arm of each cohort.
Intervention: Placebo
Treatment Cohort 2
Each study participant will be administered with one dose per day of GC021109 for 28 days. Dose levels will be determined following a review of cohort 1 safety data through day 14
Intervention: GC021109
Placebo Cohort 2
Patients receiving placebo as part of each cohort will be dosed with a comparable capsule to those in the treatment arm of each cohort.
Intervention: Placebo
Treatment Cohort 3
Each study participant will be administered with one dose per day of GC021109 for 28 days. Dose levels will be determined following a review of cohort 2 safety data through day 14
Intervention: GC021109
Placebo Cohort 3
Patients receiving placebo as part of each cohort will be dosed with a comparable capsule to those in the treatment arm of each cohort.
Intervention: Placebo
Outcomes
Primary Outcomes
Assessment of the number and severity of treatment-emergent AEs (TEAEs) following single oral doses of GC021109 and placebo from Day 1 through Day 28
Time Frame: 28 days
Secondary Outcomes
- Estimate of the pharmacokinetic (PK) parameters of multiple, escalating dose levels of GC021109: AUC0-t, AUC0-24, AUC0-inf, AUC%extrap, CL/F, Cmax, Tmax, λz, and t1/2.(28 days)
- Determine the effect of multiple, escalating dose levels of GC021109 on potential biomarkers of activities.(28 days)