Alzheimer Disease
Conditions
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.
Interventions
DRUGCT1812
Active Treatment- CT1812 at a dose of 300mg
OTHERPlacebo
Placebo Comparator
Sponsors
National Institute on Aging (NIA)
Cognition Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. 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. 2. 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 3. 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. 4. MMSE 18-26 inclusive. 5. Geriatric Depression Scale (GDS) ≤ 6 with no active depression (see Section 9.3
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | 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. | 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. | 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. |
Countries
Netherlands
Participant flow
Recruitment details
The study was conducted at a single site in the Netherlands.
Pre-assignment details
This was a single-site, randomized, double-blind, placebo-controlled, 2 period, crossover, Phase 2 study. Eligible participants were randomly assigned to receive either 300 mg/day CT1812 in Period 1 and placebo in Period 2, or placebo in Period 1 and 300 mg/day CT1812 in Period 2 after a washout period of 14 days. The duration of each period was 29 days. A total of 16 participants were randomized and 15 participants completed the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo/CT1812 Placebo Non-active study drug/Active Treatment- CT1812 at a dose of 300mg | 8 |
| CT1812/Placebo Active Treatment- CT1812 at a dose of 300mg/Placebo: Placebo Comparator | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | CT1812/Placebo | Placebo/CT1812 | Total |
|---|---|---|---|
| Age, Continuous | 67.3 years STANDARD_DEVIATION 9.69 | 65.6 years STANDARD_DEVIATION 6.19 | 66.4 years STANDARD_DEVIATION 7.9 |
| Body Mass Index at Screening | 25.723 kg/m^2 STANDARD_DEVIATION 2.6552 | 26.098 kg/m^2 STANDARD_DEVIATION 5.4119 | 25.910 kg/m^2 STANDARD_DEVIATION 4.1226 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 8 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Height at Screening | 173.3 cm STANDARD_DEVIATION 12.34 | 175.8 cm STANDARD_DEVIATION 8.1 | 174.5 cm STANDARD_DEVIATION 10.17 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
| Weight at Screening | 77.08 Kg STANDARD_DEVIATION 10.021 | 81.39 Kg STANDARD_DEVIATION 22.5 | 79.23 Kg STANDARD_DEVIATION 16.973 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 16 |
| other Total, other adverse events | 6 / 15 | 11 / 16 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 |
Outcome results
Primary
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.
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.
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
Population: Up to 16 participants were planned to be enrolled. A total of 16 participants were randomized and completed Period 1. Fifteen participants completed Period 2. Participant 3001-0031 (CT1812/placebo) withdrew consent before Period 2. A total of 15 participants completed the study as planned.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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. | Global Relative Theta Power Day 1 | 0.2133 uV^2/Hz | Standard Deviation 0.06158 |
| Placebo | 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. | Global Relative Theta Power Day 29 | 0.2276 uV^2/Hz | Standard Deviation 0.07872 |
| Placebo | 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. | Change from Day 1 to Day 29 | 0.0104 uV^2/Hz | Standard Deviation 0.0321 |
| CT1812 | 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. | Global Relative Theta Power Day 1 | 0.2071 uV^2/Hz | Standard Deviation 0.08209 |
| CT1812 | 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. | Global Relative Theta Power Day 29 | 0.1971 uV^2/Hz | Standard Deviation 0.07569 |
| CT1812 | 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. | Change from Day 1 to Day 29 | -0.0100 uV^2/Hz | Standard Deviation 0.0428 |
Primary
Changes in Predose CT1812 Plasma Concentrations.
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.
Time frame: Baseline through Day 84: Pre and Post- Dose on Days 1, 29 AND Pre Dose Days 8, 15, 22.
Population: The pharmacokinetic (PK) population was comprised of all randomized participants who received at least one dose of study drug and had at least one PK concentration of CT1812. All 16 randomized participants were included in the PK Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 1, Predose | 0.00 ng/mL | Standard Deviation 0 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 1, Post-dose | 179.64 ng/mL | Standard Deviation 136.717 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 8, Predose | 25.49 ng/mL | Standard Deviation 25.017 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 15, Predose | 14.93 ng/mL | Standard Deviation 7.826 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 22, Predose | 13.76 ng/mL | Standard Deviation 8 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 29, Predose | 14.08 ng/mL | Standard Deviation 8.984 |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 29, Post-dose | 169.20 ng/mL | Standard Deviation 246.15 |
Primary
Changes in Predose CT1812 Plasma Concentrations.
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.
Time frame: Baseline through Day 84: Pre and Post- Dose on Days 1, 29 AND Pre Dose Days 8, 15, 22.
Population: The pharmacokinetic (PK) population was comprised of all randomized participants who received at least one dose of study drug and had at least one PK concentration of CT1812. All 16 randomized participants were included in the PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 1, Post-dose | 161.50 ng/mL |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 8, Predose | 23.05 ng/mL |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 15, Predose | 13.20 ng/mL |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 22, Predose | 12.40 ng/mL |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 29, Predose | 12.60 ng/mL |
| Placebo | Changes in Predose CT1812 Plasma Concentrations. | Period Day 29, Post-dose | 96.35 ng/mL |
Primary
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
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
Time frame: Up to 126 days
Population: A total of 16 participants were randomized and completed Period 1. Fifteen participants completed Period 2. Participant 3001-0031 (CT1812/placebo) withdrew consent before Period 2. A total of 15 participants completed the study as planned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Related TEAEs | 3 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | All TEAEs | 6 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | TEAEs Leading to Treatment Discontinuation | 0 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Moderate TEAEs | 2 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | SAEs | 0 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Mild TEAEs | 4 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Related SAEs | 0 Participants |
| Placebo | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Severe TEAEs | 0 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Related SAEs | 0 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | All TEAEs | 11 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Mild TEAEs | 7 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Moderate TEAEs | 4 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Related TEAEs | 3 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | TEAEs Leading to Treatment Discontinuation | 0 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | SAEs | 0 Participants |
| CT1812 | Number of TEAEs, Related TEAEs, SAEs, and Related SAEs | Severe TEAEs | 0 Participants |