Sponsor is developing an oral formulation of CT1812 fumarate to treat AD and mild cognitive impairment. MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: CT1812
Product Code: CT1812 fumarate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: CT1812 FUMARATE
Current Sponsor code: CT1812 FUMARATE
Other descriptive name: CT1812
Concentr
Sponsors
Cognition Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men, and women of non-childbearing potential, 50-85 years of age inclusively, with a diagnosis of mild to moderate Probable Alzheimer’s Disease Dementia according to the 2011 NIA-AA criteria and at least a 6 month decline in cognitive function documented in the medical record. a. Non-childbearing potential for women is defined as postmenopausal [last natural menses greater than 24 months; in women under age 55, menopausal status will be documented with serum follicle stimulating hormone (FSH) test] or undergone a documented bilateral tubal ligation or hysterectomy b. 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 participation, 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. 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 3. MMSE 18-26 inclusive. Subjects must, in the opinion of the investigator, be able to comply with study procedures and must understand the consent process. The investigator will use his or her clinical judgment in conjunction with the cognitive screening assessments to determine whether the subject meets these criteria in a manner that is consistent with local clinical practice and standards. Subjects with borderline low MMSE at screening may undergo repeat MMSE administration if extenuating circumstances were present at original assessment. 4. A positive amyloid scan (florbetaben F18, florbetapir F18, or flutametamol F18) at screening or within prior 12 months, as read by the certified, site-designated PET scan reader. 5. Must consent to apolipoprotein E (ApoE) genotyping 6. Subjects must have a caregiver or study partner who can participate in all clinic visits. 7. Patients living at home or in the community (assisted living acceptable) 8. Able to swallow CT1812 capsules. 9. Stable pharmacological treatment of any other chronic conditions for at least 30 days prior to screening. 10. Subjects must be capable of providing either written informed consent to the study procedures and for use of protected health information [Health Insurance Portability and Accountability Act (HIPAA) Authorization, if applicable]. Written informed consent also shall be obtained from the responsible caregiver or study partner. All consent processes must be undertaken in the presence of a witness and prior to any study procedures. 11. Subjects shall be generally healthy with mobility (ambulatory or ambulatory-aided, i.e., walker or cane), vision and hearing (hearing aid permissible) sufficient for compliance with testing procedures. 12. Must be able to complete all screening evaluations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1 Hospitalization or change of chronic concomitant medication within one month prior to screening 2 Patients living in a continuous care nursing facility 3 Screening MRI of the brain indicative of significant abnormality, inter alia, prior hemorrhage or infarct >1 cm3, >3 lacunar infarcts, cerebral contusion, encephalomalacia, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g. abscess or brain tumor such as meningioma) 4 Clinical or laboratory findings consistent with: a Other primary degenerative dementia b Other neurodegenerative condition c Seizure disorder; or d Other infectious, metabolic or systemic diseases affecting the central nervous system 5 A current DSM-V diagnosis that would interfere with the subject’s ability to participate in the study 6 Any prior history of suicidal thoughts or behavior that are believed by the investigator to represent a current safety risk 7 Clinically significant, advanced or unstable disease that may interfere with outcome evaluations, such as: a Chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, > 1.5 ULN); b Respiratory insufficiency; c Renal insufficiency, defined as eGFR 100 beats/min.) e Poorly managed hypertension (systolic >160 mm Hg and/or diastolic >95 mm Hg) or hypotension (systolic 7.5 8 History of cancer within 3 years of screening exception: fully excised non-melanoma skin cancers or non-metastatic prostate cancer (stable for at least 6 months) 9 History of acute/chronic hepatitis B or C and/or carriers of hepatitis B 10 Clinically significant abnormalities in screening laboratory tests, including: a hematocrit 1.4 or other coagulopathy, confirmed by repeat analysis d lymphocyte count less than 1200/ul 11 Disability that may prevent the patient from completing all study requirements 12 Women who are of childbearing potential 13 Within 4 weeks of screening visit or during the course of 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, exceptions: a benzodiazepines must not be administered within 5 half-lives of cognitive testing; b administration of selective serotonin re-uptake inhibitors (SSRI) may be continued if stable for 60 days prior to Screening; c low dose lorazepam may be used for sedation prior to MRI scan for those patients requiring sedation. Max. 2 mg lorazepam may be used for the MRI scan 14 Any disorder that could interfere with the absorption, distribution, metabolism or excretion of drugs 15 Nootropic drugs except for AD meds (acetylcholinesterase inhibitors and memantine) stable for at least 30 days 16 Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol per day indicated by elevated MCV significantly above normal value at screening 17 Suspected or known allergy to any components of the stud
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate target engagement of CT1812 treatment by measuring the displacement of Aß oligomers into cerebrospinal fluid (CSF) and to evaluate the safety and tolerability of 100 mg of once-daily oral CT1812, administered for 6 months in participants with mild to moderate Alzheimer’s disease (AD).;Secondary Objective: Secondary: To evaluate the effect of CT1812 on Plasma and CSF proteomics and biomarkers known to be affected in AD patients through measurement of CSF Aß40, Aß42, tau, phospho-tau, neurogranin, NFL and SNAP25 To evaluate the pharmacokinetics of CT1812 through measurement of plasma and CSF concentrations of CT1812 in AD patients To evaluate the safety and tolerability of CT1812 in AD patients Exploratory: To correlate cognitive measures at screening with CSF oligomer concentrations collected at baseline. ;Primary end point(s): The primary endpoint is the change from the baseline CSF Aß oligomer concentration after dosing with CT1812 versus placebo. The change from baseline will be measured through a number of exploratory endpoints as indicated below. For each subject, the baseline CSF oligomer concentration will be computed as the average of the measurements from hours -4, -3, -2 and -1 and 0. CSF Aß Oligomer pharmacodynamic endpoints will include: Cmax Mean relative and absolute change from baseline to each sample collection time point AUC The time to peak Aß oligomer concentration (Tmax) ;Timepoint(s) of evaluation of this end point: Pharmacokinetic and Pharmacodynamic Endpoints: Day 1 to Day 2. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety Endpoints • The incidence and severity of adverse events (AE) • The incidence of serious adverse events (SAE) • Changes in vital signs • Changes in physical and neurological exam findings • Changes in body mass • Changes in electrocardiogram (ECG) findings • Changes in clinical laboratory testing (serum chemistry, hematology, urinalysis) • Changes in the Columbia Suicide Severity Rating Scale (C-SSRS) Pharmacokinetic and Pharmacodynamic Endpoints The following CT1812 pharmacokinetic parameters will be determined in plasma and CSF: • Maximum concentration (Cmax) • Time to maximum concentration (Tmax) • Area under the curve (AUClast and AUCinf) • apparent drug clearance (CL/F) (plasma only) • apparent volume of distribution in the terminal phase (Vz/F) (plasma only) • Terminal half life (t1/2) Pharmacodynamic endpoints include the effect of CT1812 on the following biomarkers in CSF: • Total-Tau • Phospho -Tau • Aß40 • Aß42 • NFL • Neurogranin • SNAP25 (synaptosomal-associated protein 25) ;Timepoint(s) of evaluation of this end point: Safety Endpoints: From screening until the end of study. | — |
Countries
Sweden, United States
Contacts
Public ContactNikola Helmberg
NeuroScios GmbH
Outcome results
None listed