Mild to Moderate Alzheimer's Disease
Conditions
Keywords
Alzheimer's Disease
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD).
Detailed description
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group 36 week multicenter Phase 2 study of two doses of CT1812 in adults with mild to moderate Alzheimer's Disease (AD). This Phase 2 study is designed to evaluate the safety of two doses of CT1812 administered once daily for 6 months in adults aged 50 to 85 who have been diagnosed with mild to moderate Alzheimer's disease. Randomized participants will receive 100 mg of CT1812, 300 mg of CT1812, or placebo once daily for 182 days. Exploratory endpoints that evaluate the effect of CT1812 on biomarkers are also included.
Interventions
DRUGCT1812
Active Study Drug
DRUGPlacebo
Non-active study drug
Sponsors
National Institute on Aging (NIA)
Cognition Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a multi-center Phase 2, randomized, double-blind, placebo-controlled, parallel-group study.
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Alzheimer's disease according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record. i) Non-childbearing potential for women is defined as postmenopausal (last natural menses greater than 24 months) or undergone a documented bilateral tubal ligation or hysterectomy. If last natural menses less than 24 months, a serum FSH value confirming post-menopausal status can be employed. ii) Male participants who are sexually active with a woman of child-bearing potential must agree to use condoms during the trial and for 3 months after last dose unless the woman is using an acceptable means of birth control. 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. Diagnostic confirmation by amyloid PET with florbetaben or another approved amyloid PET ligand. Previous amyloid imaging study with a positive result will be accepted. If none is available, then amyloid PET will be conducted during screening. Diagnostic confirmation by a CSF sample collected at the screening visit lumbar puncture in place of amyloid PET will also be acceptable 3. Neuroimaging (MRI) obtained during screening consistent with the clinical diagnosis of Alzheimer's disease and without findings of significant exclusionary abnormalities (see
Exclusion criteria
, number 4). An historical MRI, up to 1 year prior to screening, may be used as long as there is no history of intervening neurologic disease or clinical events (such as a stroke, head trauma etc.) and the subject is without clinical symptoms or signs suggestive of such intervening events.). 4. MMSE 18-26 inclusive.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Up to 210 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 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). |
| Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Up to 210 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 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Baseline to Day 182 | Change from baseline in CSF-Aβ, Tau, phospho-Tau, neurogranin, synaptotagmin, synaptosomal-associated protein-25 (SNAP25), neurofilament light chain (NfL), and Aβ-oligomers.Change from baseline is calculated as the observed value minus the baseline value. |
| Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers | Baseline to Day 182 | Ratio of Amyloid Beta 1-42 (Aβ42) to Amyloid Beta 1-40 (Aβ40) Concentration from Baseline to Day 182. |
Countries
Australia, Czechia, Netherlands, Spain, United States
Participant flow
Recruitment details
The study was conducted in 12 centers in the United States, 3 centers in Australia, 3 centers in the Netherlands, 8 centers in Czech Republic, and 4 centers in Spain.
Pre-assignment details
A total of 372 participants were screened, and 153 were randomized: 51 to CT1812 100 mg, 51 to CT1812 300 mg, and 51 to placebo. Study drug was administered to all participants in the CT1812 groups (100%) and to 50 participants (98.0%) in the placebo group. One participant in the placebo arm was randomized in error and did not receive study drug after informing the site post-randomization and prior to dosing of a prohibited concomitant medication.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatment- CT1812 100 mg CT1812 at a dose of 100 mg
CT1812: Active Study Drug | 51 |
| Active Treatment- CT1812 300 mg CT1812 at a dose of 300 mg
CT1812: Active Study Drug | 51 |
| Placebo Comparator - Placebo Placebo
Placebo: Non-active study drug | 50 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 11 | 3 |
| Overall Study | COVID 19 Pandemic | 0 | 1 | 0 |
| Overall Study | Discontinuation of the trial at the site | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
| Overall Study | Non-compliance with study drug | 0 | 0 | 1 |
| Overall Study | Randomized in error | 0 | 0 | 1 |
| Overall Study | Subject moved to another location | 1 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Active Treatment- CT1812 100 mg | Total | Placebo Comparator - Placebo | Active Treatment- CT1812 300 mg |
|---|---|---|---|---|
| Age, Continuous | 72.4 years STANDARD_DEVIATION 6.96 | 72.7 years STANDARD_DEVIATION 7.39 | 71.6 years STANDARD_DEVIATION 7.97 | 74.1 years STANDARD_DEVIATION 7.14 |
| BMI | 26.04 kg/m^2 STANDARD_DEVIATION 4.574 | 24.87 kg/m^2 STANDARD_DEVIATION 3.846 | 24.13 kg/m^2 STANDARD_DEVIATION 3.046 | 24.43 kg/m^2 STANDARD_DEVIATION 3.554 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 11 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants | 140 Participants | 49 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Height | 165.77 cm STANDARD_DEVIATION 9.143 | 166.39 cm STANDARD_DEVIATION 10.335 | 167.52 cm STANDARD_DEVIATION 9.998 | 165.88 cm STANDARD_DEVIATION 11.802 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 50 Participants | 146 Participants | 47 Participants | 49 Participants |
| Sex: Female, Male Female | 34 Participants | 91 Participants | 28 Participants | 29 Participants |
| Sex: Female, Male Male | 17 Participants | 61 Participants | 22 Participants | 22 Participants |
| Weight | 72.01 Kg STANDARD_DEVIATION 15.105 | 69.33 Kg STANDARD_DEVIATION 13.77 | 68.10 Kg STANDARD_DEVIATION 12.672 | 67.85 Kg STANDARD_DEVIATION 13.268 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 51 | 0 / 51 | 1 / 50 |
| other Total, other adverse events | 25 / 51 | 25 / 51 | 33 / 50 |
| serious Total, serious adverse events | 2 / 51 | 3 / 51 | 5 / 50 |
Outcome results
Primary
Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs)
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 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT).
Time frame: Up to 210 Days
Population: Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 36 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Mild TEAEs | 19 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Moderate TEAEs | 16 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Severe TEAEs | 1 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Severe TEAEs | 4 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 42 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Moderate TEAEs | 16 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Mild TEAEs | 22 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Severe TEAEs | 3 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Mild TEAEs | 22 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | Moderate TEAEs | 14 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Mild, Moderate, or Severe Treatment Emergent Adverse Events (TEAEs) | All TEAEs | 39 Participants |
Primary
Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (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 27.0.TEAEs are events that occurred or worsened on or after the first application of study drug. Participants are counted once for each system organ class (SOC) and once for each preferred term (PT).
Time frame: Up to 210 Days
Population: Data are based on the safety population, which is defined as all participants who received one or more doses of the study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE | 36 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE related to treatment | 11 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to study drug discontinuation | 0 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to death | 0 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE | 2 Participants |
| Active Treatment- CT1812 100 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE related to treatment | 0 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE related to treatment | 1 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE | 42 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to death | 0 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE | 3 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE related to treatment | 16 Participants |
| Active Treatment- CT1812 300 mg | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to study drug discontinuation | 11 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE related to treatment | 7 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to study drug discontinuation | 3 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE related to treatment | 0 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with a TEAE leading to death | 1 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one TEAE | 39 Participants |
| Placebo Comparator - Placebo | Number of Study Participants With at Least One Treatment Emergent Adverse Events (TEAs) and Serious Adverse Events (SAEs). | Participants with at least one SAE | 5 Participants |
Secondary
Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers
Ratio of Amyloid Beta 1-42 (Aβ42) to Amyloid Beta 1-40 (Aβ40) Concentration from Baseline to Day 182.
Time frame: Baseline to Day 182
Population: The analyzed population represents the number of subjects in the Efficacy modified intent-to-treat (mITT) population and participants who had both baseline and Day 182 CSF samples collected.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Treatment- CT1812 100 mg | Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers | 0.019 ratio | Standard Deviation 0.0766 |
| Active Treatment- CT1812 300 mg | Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers | -0.024 ratio | Standard Deviation 0.0631 |
| Placebo Comparator - Placebo | Amyloid Beta 1-42/Amyloid Beta 1-40 (Aβ42/40) in the Cerebrospinal Fluid (CSF) Biomarkers | -0.002 ratio | Standard Deviation 0.0594 |
Secondary
Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers
Change from baseline in CSF-Aβ, Tau, phospho-Tau, neurogranin, synaptotagmin, synaptosomal-associated protein-25 (SNAP25), neurofilament light chain (NfL), and Aβ-oligomers.Change from baseline is calculated as the observed value minus the baseline value.
Time frame: Baseline to Day 182
Population: The analyzed population represents the number of subjects in the Efficacy modified intent-to-treat (mITT) population and participants who had both baseline and Day 182 CSF samples collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Alpha Synuclein Protein (ASYNP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | 48.6 ng/L | Standard Deviation 625.13 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-40 (Aβ40) (ng/L) -Concentration change in CSF from Baseline to Day 182 | -573.9 ng/L | Standard Deviation 2228.8 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-42 (Aβ42) (ng/L) -Concentration change in CSF from Baseline to Day 182 | -13.5 ng/L | Standard Deviation 105.66 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Glial Fibrillary Acidic Protein (GFAP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -81.9 ng/L | Standard Deviation 457.85 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurofilament Light Chain Protein (NFLP) (ng/L) Concentration change in CSF from Baseline to Day 182 | 72.8 ng/L | Standard Deviation 317.59 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurogranin (NRGR) (ng/L) - Concentration change in CSF from Baseline to Day 182 | 19.70 ng/L | Standard Deviation 82.557 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Phosphorylated Tau Protein 181 (pTau181) (ng/L) Concentration change in CSF from Baseline to Day 182 | -0.74 ng/L | Standard Deviation 37.227 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptosomal-Associated Protein 25 (SNAP25) Concentration change in CSF from Baseline to Day 182 | -0.88 ng/L | Standard Deviation 6.485 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptotagmin (SYN) Concentration change in CSF from Baseline to Day 182 | 0.75 ng/L | Standard Deviation 15.041 |
| Active Treatment- CT1812 100 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Tau Protein (TPROT) (ng/L) Concentration change in CSF from Baseline to Day 182 | -8.4 ng/L | Standard Deviation 204.92 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptotagmin (SYN) Concentration change in CSF from Baseline to Day 182 | -19.44 ng/L | Standard Deviation 98.693 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Alpha Synuclein Protein (ASYNP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | 38.3 ng/L | Standard Deviation 213.1 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurogranin (NRGR) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -22.77 ng/L | Standard Deviation 68.348 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurofilament Light Chain Protein (NFLP) (ng/L) Concentration change in CSF from Baseline to Day 182 | -55.5 ng/L | Standard Deviation 262.24 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-40 (Aβ40) (ng/L) -Concentration change in CSF from Baseline to Day 182 | -1076.7 ng/L | Standard Deviation 1781.36 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Tau Protein (TPROT) (ng/L) Concentration change in CSF from Baseline to Day 182 | -47.8 ng/L | Standard Deviation 358.68 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptosomal-Associated Protein 25 (SNAP25) Concentration change in CSF from Baseline to Day 182 | -1.64 ng/L | Standard Deviation 4.767 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-42 (Aβ42) (ng/L) -Concentration change in CSF from Baseline to Day 182 | -72.1 ng/L | Standard Deviation 121.62 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Phosphorylated Tau Protein 181 (pTau181) (ng/L) Concentration change in CSF from Baseline to Day 182 | -9.76 ng/L | Standard Deviation 45.506 |
| Active Treatment- CT1812 300 mg | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Glial Fibrillary Acidic Protein (GFAP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -87.4 ng/L | Standard Deviation 176.01 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptosomal-Associated Protein 25 (SNAP25) Concentration change in CSF from Baseline to Day 182 | -1.04 ng/L | Standard Deviation 3.763 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Glial Fibrillary Acidic Protein (GFAP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -69.1 ng/L | Standard Deviation 321.21 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurofilament Light Chain Protein (NFLP) (ng/L) Concentration change in CSF from Baseline to Day 182 | 297.7 ng/L | Standard Deviation 535.6 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Neurogranin (NRGR) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -16.93 ng/L | Standard Deviation 44.348 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Synaptotagmin (SYN) Concentration change in CSF from Baseline to Day 182 | 4.66 ng/L | Standard Deviation 56.365 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Phosphorylated Tau Protein 181 (pTau181) (ng/L) Concentration change in CSF from Baseline to Day 182 | -4.03 ng/L | Standard Deviation 13.185 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Alpha Synuclein Protein (ASYNP) (ng/L) - Concentration change in CSF from Baseline to Day 182 | -831.2 ng/L | Standard Deviation 3056.97 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Tau Protein (TPROT) (ng/L) Concentration change in CSF from Baseline to Day 182 | -9.4 ng/L | Standard Deviation 80.67 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-40 (Aβ40) (ng/L) -Concentration change in CSF from Baseline to Day 182 | -17.9 ng/L | Standard Deviation 1633.79 |
| Placebo Comparator - Placebo | Change From Baseline in the Cerebrospinal Fluid (CSF) Biomarkers | Amyloid Beta 1-42 (Aβ42) (ng/L) -Concentration change in CSF from Baseline to Day 182 | 3.1 ng/L | Standard Deviation 90.9 |