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Alzheimer DiseasePhase 2NCT04735536

Pilot Clinical Study of CT1812 in Mild to Moderate Alzheimer's Disease Using EEG

A Phase 2 study testing CT1812 in people with Alzheimer Disease, run by Cognition Therapeutics at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 50 to 85 years
Conditions the study is for
Alzheimer Disease
What is being tested?
CT1812
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
1 siteNetherlands
Study dates
9 Jul 2020to 26 Apr 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 50 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
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  • 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).
  • Participants must have no known history of difficulty swallowing capsules.
  • Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening.
  • Must consent to apolipoprotein E (APOE) genotyping.
  • Participants shall be generally healthy with mobility (ambulatory or ambulatory-aided, ie, walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures.
  • Must be able to complete all screening evaluations.

Who cannot join

  • 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).
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  • 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.
  • 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,
  • Heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 6 months before screening).
  • 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 (HbA1c) > 7.5.
  • History of cancer within 3 years of screening with the exception of fully excised non-melanoma skin cancers or non-metastatic prostate cancer that has been stable for at least 6 months.
  • Seropositive for human immunodeficiency virus (HIV).
  • History of acute/chronic hepatitis B or C and/or carriers of hepatitis B (seropositive for hepatitis B surface antigen [HbsAg] or anti-hepatitis C [HCV] antibody).
  • 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; international normalized ratio (INR) > 1.4 or other coagulopathy, confirmed by repeat assessment.
  • Disability that may prevent the participant from completing all study requirements (e.g., blindness, deafness, severe language difficulty, etc).
  • Within 4 weeks of screening visit or during the study, concurrent treatment with antipsychotic agents, antiepileptics, centrally active anti-hypertensive drugs (e.g., clonidine, l-methyl dopa, guanidine, guanfacine, etc), sedatives, opioids, mood stabilizers (e.g., valproate, lithium); 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.
  • Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs (eg, small bowel disease, Crohn's disease, celiac disease, or liver disease).
  • Nootropic drugs except stable AD meds (acetylcholinesterase inhibitors and memantine).
  • Suspected or known drug or alcohol abuse, ie, more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day.
  • Suspected or known allergy to any components of the study treatments.
  • Enrollment in another investigational study or intake of investigational drug within the previous 30 days or 5 half-lives of the investigational drug, whichever is longer.
  • Intake of drugs or substances potentially involved in clinically significant induction or inhibition of CYP3A4 or P-gp mediated drug interactions with CT1812, within 4 weeks or 5 half-lives of the interacting drug prior to administration of CT1812 and throughout the study. Grapefruit juice should be avoided in the 2 weeks prior to dosing and throughout the study. See Appendix A for a complete list of prohibited substances.
  • Exposure to immunomodulators, anti Aβ vaccines, passive immunotherapies for AD (e.g., monoclonal antibodies) within the past 180 days and/or exposure to BACE inhibitors within the past 30 days
  • Anticipated use of nonsteroidal anti-inflammatory drugs (NSAIDs) on more than 14 days from Baseline/Day 1 to Day 182. Contraindication to undergoing an LP including, but not limited to: inability to tolerate an appropriately flexed position for the time necessary to perform an LP; international normalized ratio (INR) > 1.4 or other coagulopathy; platelet count of < 120,000/μL; infection at the desired LP site; taking anti-coagulant medication within 90 days of screening (low-dose aspirin is permitted); degenerative arthritis of the lumbar spine; suspected non-communicating hydrocephalus or intracranial mass; prior history of spinal mass or trauma.
  • Any condition, which in the opinion of the Investigator or the Sponsor, makes the participant unsuitable for inclusion.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site
  • Brain Research Center

    Amsterdam

Other trials in Netherlands

About this study

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

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.

Read the 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.

Being tested
CT1812, Placebo
Medical subject headings
Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CT1812Drug

    Active Treatment- CT1812 at a dose of 300mg

  • PlaceboOther

    Placebo Comparator

Study groups in NCT04735536
Study groupRoleWhat they receive
Active Treatment- CT1812ExperimentalActive Treatment- CT1812 at a dose of 300mg
Receives: Drug: CT1812; Other: Placebo
Control - PlaceboPlacebo comparatorDrug: Placebo Non-active study drug
Receives: Drug: CT1812; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 126 days

  2. 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.

    Measured: Day 1 through Day 29 of Period 1 and Day 1 (study day 44) and Day 29 (study day 72) of Period 2

  3. 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.

    Measured: Baseline through Day 84: Pre and Post- Dose on Days 1, 29 AND Pre Dose Days 8, 15, 22.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Feb 2021
  2. Study start9 Jul 2020
  3. Primary completion26 Apr 2023
  4. Study completion26 Apr 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04735536
Sponsor's protocol ID
COG0202
Other IDs
RF1AG058710, 2019-003552-36, 2019
Status last verified
Nov 2024
First submitted
30 Jan 2020
Last updated
29 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Vijverberg E, de Haan W, Scheijbeler E, Hamby ME, Catalano S, Scheltens P, Grundman M, Caggiano AO. A Pilot Electroencephalography Study of the Effect of CT1812 Treatment on Synaptic Activity in Patients with Mild to Moderate Alzheimer's Disease. J Prev Alzheimers Dis. 2024;11(6):1809-1817. doi: 10.14283/jpad.2024.154.

    PubMed 39559892

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CT1812 in people with Alzheimer Disease, run by Cognition Therapeutics at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of TEAEs, Related TEAEs, SAEs, and Related SAEs (time frame: Up to 126 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04735536, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2024.

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