A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects With Mild to Moderate Alzheimer's Disease
Overview
- Phase
- Phase 2
- Intervention
- CT1812
- Conditions
- Alzheimer Disease
- Sponsor
- Cognition Therapeutics
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This is a single-site, randomized, double-blind, placebo-controlled, 29-day, 2-period crossover Phase 2 study of 1 dose level of CT1812 (active) or placebo in adults with mild to moderate AD.
Detailed Description
This is a single-site, randomized, double-blind, placebo-controlled, 29-day, 2-period crossover Phase 2 study of 1 dose level of CT1812 (active) or placebo in adults with mild to moderate AD. 16 participants (8 randomized to 300 mg CT1812, 8 randomly assigned to placebo during each treatment period): the 8 participants randomly assigned to CT1812 in Treatment Period 1 will receive placebo in Treatment Period 2; the 8 participants randomly assigned to placebo in Treatment Period 1 will receive CT1812 in Treatment Period 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Women of non-childbearing potential and men, aged 50 to 85 years, inclusive, with a diagnosis of mild to moderate Alzheimer's disease according to the 2018 NIA-AA criteria and at least a 6-month history of decline in cognitive function documented in the medical record.
- •i) Non-childbearing potential for women is defined as postmenopausal (last menses greater than 24 months) or undergone a documented bilateral tubal ligation or hysterectomy. If last menses less than 24 months, a serum follicle stimulating hormone (FSH) value confirming post-menopausal status may be used.
- •ii) Male participants who are sexually active with a woman of child-bearing potential must agree to use condoms during the study and for 3 months after last dose. Female partners should also consider using an acceptable means of birth control, though it is not mandatory. Acceptable forms of birth control include abstinence, birth control pills, or any double combination of: intrauterine device (IUD), male or female condom, diaphragm, sponge, and cervical cap.
- •CSF positive for amyloid beta (as defined in the study manual). Historical CSF results will be considered provided the results are consistent with the CSF amyloid beta threshold required for inclusion and following discussion with the medical monitor; however, an LP is still required as part of screening procedures
- •Neuroimaging (MRI) consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see Section 9.3 exclusion criteria no. 4). An historical MRI, up to 1 year prior to screening, may be used as long as there have been no interval clinical neurologic events that may suggest a change in the MRI scan.
- •MMSE 18-26 inclusive.
- •Geriatric Depression Scale (GDS) ≤ 6 with no active depression (see Section 9.3 exclusion criteria no. 6).
- •Formal education of 8 or more years.
- •Participants must have a caregiver/study partner who in the opinion of the site's Principal Investigator, has contact with the study participant for a sufficient number of hours per week to provide informative responses on the protocol assessments, oversee the administration of study drug, and is willing and able to participate in all study site visits and some study assessments. The caregiver/ study partner must provide written informed consent to participate in the study.
- •Participants living at home or in the community (assisted living acceptable).
Exclusion Criteria
- •Hospitalization (except for planned procedures) or change of chronic concomitant medication within 1 month prior to screening.
- •Participants living in a continuous care nursing facility.
- •Contraindications to the MRI examination for any reason.
- •Screening MRI (or historical MRI, if applicable) of the brain indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct \> 1 cm3, \> 3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (eg, abscess or brain tumor such as meningioma).
- •Clinical or laboratory findings consistent with:
- •Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down syndrome, etc).
- •Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc).
- •Seizure disorder.
- •Other infectious, metabolic or systemic diseases affecting the central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, other laboratory values etc).
- •A current DSM-V diagnosis of active major depression, schizophrenia or bipolar disorder. Participants with depressive symptoms successfully managed by a stable dose of an antidepressant are allowed entry.
Arms & Interventions
Active Treatment- CT1812
Active Treatment- CT1812 at a dose of 300mg
Intervention: CT1812
Active Treatment- CT1812
Active Treatment- CT1812 at a dose of 300mg
Intervention: Placebo
Control - Placebo
Drug: Placebo Non-active study drug
Intervention: CT1812
Control - Placebo
Drug: Placebo Non-active study drug
Intervention: Placebo
Outcomes
Primary Outcomes
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Time Frame: Up to 126 days
Adverse events were captured from the start of study-related procedures at Visit 1 (including diagnostic assessments or signing of ICF) onward during the course of this study. Adverse events were coded using MedDRA Version 22.0
Change in the Brain Activity Reflected by Changes of Spectral Power in Conventional Frequency Bands Measured by the Global Relative Theta (4-8 Hz) Power Obtained Through EEG Assessment.
Time Frame: Day 1 through Day 29 of Period 1 and Day 1 (study day 44) and Day 29 (study day 72) of Period 2
Global relative theta power was quantified and summarized descriptively (observed values, change from the pre-treatment values) by treatment and time point using the Safety Population. The change from period baseline in global relative theta power within each period was analyzed using a linear mixed model with fixed effects for treatment group (CT1812 or placebo), sequence, and period, and a random effect for subject within sequence. The analysis was conducted using PROC MIXED. The ability of CT1812 to rapidly restore synapse number to normal was expected to result in a decrease in EEG theta power in AD patients in response to short-term treatment with CT1812. Thus, a decrease in the Global Relative Theta Power represents better outcomes, while high values in the Global Relative Theta Power represent worse outcomes. The unit is represented by uV\^2/Hz (microvolt squared per frequency). This is a common unit for spectral power density, and how relative power measures are displayed.
Changes in Predose CT1812 Plasma Concentrations.
Time Frame: Baseline through Day 84: Pre and Post- Dose on Days 1, 29 AND Pre Dose Days 8, 15, 22.
For the measurements of pre-dose and post-dose plasma concentrations of CT1812, samples were collected 1± 0.25 hour predose. Single concentrations of CT1812 at selected predose and post-dose time points were reported.