A Pilot Electroencephalography (EEG) Study to Evaluate the Effect of CT1812 Treatment on Synaptic Activity in Subjects With Mild to Moderate Alzheimer*s Disease

Phase 2

Completed

• Conditions: Dementia; Alzheimer's Disease; 10012272

• Registration Number: NL-OMON54794
• Lead Sponsor: Julius Clinical

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 16

Inclusion Criteria

Participants may be included in the study only if they meet all the following
criteria:
1) Women of non-childbearing potential and men, aged 50 to 85 years, inclusive,
with a
diagnosis of mild to moderate Probable Alzheimer*s Disease Dementia, according
to
the NIA-AA 2018 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) confirming post-menopausal status will be
determined.
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 meets CSF abeta 1*42 (abeta) and p-tau -181 criteria as defined below.
CSF abeta 1*42 < 1000pg/ml (Elecsys assay) AND
CSF p*tau 181 > 19 pg/ml (Elecsys Assay)
OR:
CSF abeta 1*42 < 1000pg/ml (Elecsys assay) AND
p*tau *181 / abeta 1*42 ratio > 0.020
OR:
CSF p*tau 181 > 19 pg/ml (Elcsys Assay) AND
p*tau *181 / abeta 1*42 ratio > 0.020
Historical CSF results will be considered provided the results are consistent
with the
CSF thresholds required for inclusion and following discussion with the medical
monitor; however, a lumbar puncture 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 exclusion
criteria,
number 4). A historical MRI, up to 1 year prior to screening, may be used as
long as
there have been no interval clinical neurologic events which may suggest a
change in
the MRI scan.
4) MMSE score of 18 to 26, inclusive.
5) No active depression and a GDS <= 6 (see exclusion criteria number 6).
6) Formal education of 8 or more years.
7) 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.
8) Participants living at home or in the community (assisted living
acceptable).
9) Participants must have no known history of difficulty swallowing capsules.
10) Stable pharmacological treatment of any other chronic conditions for at
least 30 days
prior to screening.
11) Must consent to apolipoprotein E (APOE) genotyping.
12) Participants shall be generally healthy with mobility (ambulatory or
ambulatory-aided,
i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient
for

Exclusion Criteria

1) Hospitalization (except for planned procedures) or change of chronic
concomitant medication within 1 month prior to screening
2) Participants living in a continuous care nursing facility
3) Contraindications to the MRI examination for any reason
4) 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
5) Clinical or laboratory findings consistent with:
-Other primary degenerative dementia
-Other neurodegenerative condition
-Seizure disorder
-Other infectious, metabolic or systemic diseases affecting the central nervous
system
6) 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.
7) Clinically significant, advanced or unstable disease that may interfere with
outcome evaluations, such as:
-Chronic liver disease, liver function test abnormalities or other signs of
hepatic insufficiency (ALT, AST, alkaline phosphatase > 1.5 ULN, lactate
dehydrogenase (LDH) > 1.5 x ULN).
-Respiratory insufficiency.
-Renal insufficiency eGFR < 50 mL/min based on the CKD-EPI formula,
https://www.mdcalc.com/ckd-epi-equations-glomerular-filtration-rate-gfr
-Heart disease.
-Bradycardia (< 50/min.) or tachycardia (> 100/min.).
-Poorly managed hypertension (systolic > 160 mm Hg and/or diastolic > 95
mm Hg) or hypotension (systolic < 90 mm Hg and/or diastolic < 60 mm Hg)
-Uncontrolled diabetes in known diabetics, as defined by hemoglobin A1c > 7.5
8) History of cancer within 3 years of screening with the exception of fully
excised nonmelanoma skin cancers or non-metastatic prostate cancer that has
been stable for at least 6 months
9) Seropositive for human immunodeficiency virus
10) History of acute/chronic hepatitis B or C and/or carriers of hepatitis B
11) Clinically significant abnormalities in screening laboratory tests,
including:
Hematocrit less than 35% for males and less than 32% for females, absolute
neutrophil cell count of <1500/uL (with the exception of a documented history
of a chronic benign neutropenia), or platelet cell count of < 120,000/uL;
INR > 1.4 or other coagulopathy, confirmed by repeat assessment of:
-Hematocrit
-Neutrophil count
-Platelet count
12) Disability that may prevent the participant from completing all study
requirements
13) Within 4 weeks of screening visit or during the study, concurrent treatment
with antipsychotic agents, antiepileptics, centrally active anti-hypertensive
drugs, sedatives, opioids, mood stabilizers; or benzodiazepines, with the
following exception:
-Low dose lorazepam may be used for sedation prior to MRI scan for those
participants requiring sedation. At the discretion of the Investigator, 0.5 to
1 mg may be given orally prior to scan with a single repeat dose given if the
first dose is ineffective. No more than a total of 2 mg lorazepam may be used
for the MRI scan
14) Any disorder that could interfere with the absorption, distribution,

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Safety will be assessed via the monitoring of<br /><br>• Adverse events.<br /><br>• Physical examinations.<br /><br>• Vital signs - BP, heart rate and body temperature.<br /><br>• Electrocardiogram (ECG).<br /><br>• Clinical laboratory tests:<br /><br>o Blood chemistry<br /><br>o Hematology<br /><br>o Urinalysis<br /><br>o Plasma.<br /><br>• Affective and cognitive measures:<br /><br>o Columbia Suicide Severity Rating Scale (C-SSRS).<br /><br>o ADAS-Cog-14, ADCS-CGIC, A-IADL-Q, and an NTB that includes CFT, COWAT, TMT<br /><br>Parts A & B, and VMDS.<br /><br>Pharmacokinetic assessments include:<br /><br>• Serum CT1812 concentrations at specified timepoint. (See Table 1 - Schedule<br /><br>of Assessments).<br /><br>• CSF: concentration of CT1812 at trough (24-hour postdose).<br /><br>Pharmacodynamics assessments include:<br /><br>• Analyses of plasma and CSF for biomarkers of target engagement or disease<br /><br>modification.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>NA</p><br>