Trial Outcomes & Findings for Pilot Clinical Study of CT1812 in Mild to Moderate Alzheimer's Disease Using EEG (NCT NCT04735536)
NCT ID: NCT04735536
Last Updated: 2024-11-29
Results Overview
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
COMPLETED
PHASE2
16 participants
Up to 126 days
2024-11-29
Participant Flow
The study was conducted at a single site in the Netherlands.
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.
Participant milestones
| Measure |
First Placebo Non-active Study Drug, Then Active Treatment With CT1812 at a Dose of 300mg
CT1812 was provided to participants as two hydroxypropyl methylcellulose (HPMC) capsules each containing 150 mg of CT1812. Matching placebo capsules containing lactose monohydrate were provided. CT1812 or matching placebo capsules were to be administered orally as a single daily dose for 29 days. Each dose CT1812 or matching placebo consisted of 2 capsules. All participants ingested the first dose at the study site and were observed for 2 hours. Capsules were swallowed with approximately 240 mL of water with or without food.
|
First Active Treatment With CT1812 at a Dose of 300mg, Then Placebo Non-active Study Drug
CT1812 was provided to participants as two hydroxypropyl methylcellulose (HPMC) capsules each containing 150 mg of CT1812. Matching placebo capsules containing lactose monohydrate were provided. CT1812 or matching placebo capsules were to be administered orally as a single daily dose for 29 days. Each dose CT1812 or matching placebo consisted of 2 capsules. All participants ingested the first dose at the study site and were observed for 2 hours. Capsules were swallowed with approximately 240 mL of water with or without food.
|
|---|---|---|
|
Period 1
STARTED
|
8
|
8
|
|
Period 1
COMPLETED
|
8
|
8
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
|
Period 2
STARTED
|
8
|
7
|
|
Period 2
COMPLETED
|
8
|
7
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Clinical Study of CT1812 in Mild to Moderate Alzheimer's Disease Using EEG
Baseline characteristics by cohort
| Measure |
Placebo/CT1812
n=8 Participants
Placebo Non-active study drug/Active Treatment- CT1812 at a dose of 300mg
|
CT1812/Placebo
n=8 Participants
Active Treatment- CT1812 at a dose of 300mg/Placebo: Placebo Comparator
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.6 years
STANDARD_DEVIATION 6.19 • n=5 Participants
|
67.3 years
STANDARD_DEVIATION 9.69 • n=7 Participants
|
66.4 years
STANDARD_DEVIATION 7.90 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Height at Screening
|
175.8 cm
STANDARD_DEVIATION 8.10 • n=5 Participants
|
173.3 cm
STANDARD_DEVIATION 12.34 • n=7 Participants
|
174.5 cm
STANDARD_DEVIATION 10.17 • n=5 Participants
|
|
Body Mass Index at Screening
|
26.098 kg/m^2
STANDARD_DEVIATION 5.4119 • n=5 Participants
|
25.723 kg/m^2
STANDARD_DEVIATION 2.6552 • n=7 Participants
|
25.910 kg/m^2
STANDARD_DEVIATION 4.1226 • n=5 Participants
|
|
Weight at Screening
|
81.39 Kg
STANDARD_DEVIATION 22.500 • n=5 Participants
|
77.08 Kg
STANDARD_DEVIATION 10.021 • n=7 Participants
|
79.23 Kg
STANDARD_DEVIATION 16.973 • n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 126 daysPopulation: 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.
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
Outcome measures
| Measure |
Placebo
n=15 Participants
Non-active study drug
|
CT1812
n=16 Participants
Active Treatment- CT1812 at a dose of 300mg
|
|---|---|---|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Related SAEs
|
0 Participants
|
0 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
All TEAEs
|
6 Participants
|
11 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Mild TEAEs
|
4 Participants
|
7 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Moderate TEAEs
|
2 Participants
|
4 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Severe TEAEs
|
0 Participants
|
0 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
Related TEAEs
|
3 Participants
|
3 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
TEAEs Leading to Treatment Discontinuation
|
0 Participants
|
0 Participants
|
|
Number of TEAEs, Related TEAEs, SAEs, and Related SAEs
SAEs
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 through Day 29 of Period 1 and Day 1 (study day 44) and Day 29 (study day 72) of Period 2Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=15 Participants
Non-active study drug
|
CT1812
n=16 Participants
Active Treatment- CT1812 at a dose of 300mg
|
|---|---|---|
|
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
|
0.2071 uV^2/Hz
Standard Deviation 0.08209
|
|
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
|
0.1971 uV^2/Hz
Standard Deviation 0.07569
|
|
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 0.03210
|
-0.0100 uV^2/Hz
Standard Deviation 0.04280
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=16 Participants
Non-active study drug
|
CT1812
Active Treatment- CT1812 at a dose of 300mg
|
|---|---|---|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 1, Predose
|
0.00 ng/mL
Standard Deviation 0.000
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 1, Post-dose
|
179.64 ng/mL
Standard Deviation 136.717
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 8, Predose
|
25.49 ng/mL
Standard Deviation 25.017
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 15, Predose
|
14.93 ng/mL
Standard Deviation 7.826
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 22, Predose
|
13.76 ng/mL
Standard Deviation 8.000
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 29, Predose
|
14.08 ng/mL
Standard Deviation 8.984
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 29, Post-dose
|
169.20 ng/mL
Standard Deviation 246.150
|
—
|
PRIMARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Placebo
n=16 Participants
Non-active study drug
|
CT1812
Active Treatment- CT1812 at a dose of 300mg
|
|---|---|---|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 1, Post-dose
|
161.50 ng/mL
Interval 4.1 to 406.0
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 8, Predose
|
23.05 ng/mL
Interval 2.5 to 106.0
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 15, Predose
|
13.20 ng/mL
Interval 2.9 to 28.6
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 22, Predose
|
12.40 ng/mL
Interval 3.6 to 28.8
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 29, Predose
|
12.60 ng/mL
Interval 2.6 to 36.0
|
—
|
|
Changes in Predose CT1812 Plasma Concentrations.
Period Day 29, Post-dose
|
96.35 ng/mL
Interval 7.5 to 949.0
|
—
|
Adverse Events
Placebo
CT1812
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=15 participants at risk
Placebo Non-active study drug
|
CT1812
n=16 participants at risk
Active Treatment- CT1812 at a dose of 300mg/Placebo
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
6.7%
1/15 • Number of events 1 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15 • Number of events 1 • 126 days
|
12.5%
2/16 • Number of events 2 • 126 days
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
1/15 • Number of events 1 • 126 days
|
0.00%
0/16 • 126 days
|
|
Injury, poisoning and procedural complications
Bone contusion
|
0.00%
0/15 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Injury, poisoning and procedural complications
Burns first degree
|
6.7%
1/15 • Number of events 1 • 126 days
|
0.00%
0/16 • 126 days
|
|
Injury, poisoning and procedural complications
Post procedural contusion
|
6.7%
1/15 • Number of events 1 • 126 days
|
0.00%
0/16 • 126 days
|
|
Injury, poisoning and procedural complications
Procedural headache
|
6.7%
1/15 • Number of events 1 • 126 days
|
18.8%
3/16 • Number of events 3 • 126 days
|
|
Investigations
Blood creatinine increased
|
0.00%
0/15 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Investigations
Hepatic enzyme increased
|
0.00%
0/15 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Nervous system disorders
Headache
|
0.00%
0/15 • 126 days
|
12.5%
2/16 • Number of events 2 • 126 days
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/15 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Vascular disorders
Hematoma
|
6.7%
1/15 • Number of events 1 • 126 days
|
12.5%
2/16 • Number of events 2 • 126 days
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/15 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Infections and infestations
Corona virus infection
|
6.7%
1/15 • Number of events 1 • 126 days
|
6.2%
1/16 • Number of events 1 • 126 days
|
|
Infections and infestations
Pneumonia
|
6.7%
1/15 • Number of events 1 • 126 days
|
0.00%
0/16 • 126 days
|
Additional Information
Chief Medical Officer, Head of R&D
Cogntion Therapeutics Inc
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place