Mild cognitive impairment due to Alzheimer's Disease or mild Alzheimer's Disease. MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852 MedDRA version: 21.1 Level: LLT Classification code 10009846 Term: Cognitive impairment System Organ Class: 100000004852
Conditions
Interventions
Product Name: T817MA
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Edonerpic
CAS Number: 519187-97-4
Other descriptive name: T-817MA
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
FUJIFILM Toyama Chemical Co., Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be eligible for enrolment: 1. Male or female, age 50 to 80 inclusive at date of ICF signature. 2. Diagnosis by the investigator of a clinical syndrome of cognitive impairment consistent with either MCI due to AD or mild AD per NIA-AA diagnostic criteria (Jack et al., 2018), with MMSE 24 to 30 (inclusive). 3. CSF results at screening consistent with the presence of Aß1-42 and p-tau181 abnormality (=1000 pg/ml for Aß1-42, =19 pg/ml for ptau181) or (p-tau181/Aß1-42 ratio >0.020 for patients with p-tau181 = 19 pg/ml and 1000=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: Patients meeting any of the following criteria must not be included in the study: 1. Has had an MRI of the brain within the previous 2 years that showed pathology that would be inconsistent with a diagnosis of AD 2. Use of prohibited medications, including memantine 3. Has any contraindications for MRI including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI 4. Has any contraindications to lumbar puncture 5. Pregnant or breastfeeding woman 6. Psychiatric disorder such as schizophrenia or dementia not of the Alzheimer’s type according to the criteria of DSM-5 7. Other neurodegenerative diseases, including Parkinson’s disease and Huntington’s disease, or cerebral tumor 8. Dementia other than AD 9. History of untreated thyroid disorder, Type I diabetes, and insulindependent or uncontrolled Type II diabetes, as determined by the investigator (except non-insulincontrolled Type II diabetes, whose HbA1c value must be below 8.0 %). The HbA1c value should not be older than 6 months prior to screening. If no recent HbA1c value is available, then HbA1c should be assessed locally. 10. History of a seizure disorder or stroke, unless >5 years ago 11. History of alcohol abuse or dependence or drug abuse in the past 5 years 12. Uncorrected impairment of vision or hearing that would preclude the patient from taking tests or patients lacking the ability to communicate 13. Clinically significant abnormal laboratory values in the opinion of the investigator 14. Severe hepatic or severe renal impairment (e.g. bilirubin > 3 x ULN, AST/ALT > 5 x ULN, eGFR 1 cm) infarct, >2 lacunar infarcts outside the brain stem, severe white matter changes (Fazekas grade 3), >4 microbleeds, superficial hemosiderosis >1 cm, aneurysm, vascular malformation, subdural hematoma, hydrocephalus, space-occupying lesion (e.g, abscess or brain tumor such as meningioma).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the neuroprotective effect of T-817MA on Tau protein phosphorylated at threonine 181 (p-tau181) in CSF compared with placebo, in patients with a diagnosis of MCI due to AD or mild AD, according to the National Institute on Aging - Alzheimer Association (NIA-AA) criteria, with a Mini Mental Status Examination (MMSE) score of 24 to 30 (inclusive), and Aß1-42 and p-tau181 abnormality in CSF (=1000 pg/ml for Aß1-42, =19 pg/ml for p-tau181) or (p-tau181/Aß1-42 ratio >0.020 for patients with p-tau181 =19 pg/ml and 1000<Aß1-42<1700 pg/ml).;Secondary Objective: To evaluate in patients on T-817MA and placebo: • cognitive function measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and Cognitive Functional Composite (CFC) • AD-related biomarkers in CSF (Tau protein phosphorylated at threonine 217 [p-tau217], total tau, Aß1-40, Aß1-42, neurofilament light [NFL], neurogranin, YKL-40 and Aß1-42/Aß1-40 ratio) and in plasma (Aß1-40, Aß1-42, NFL, glial fibrillary acidic protein [GFAP], p-tau181, p-tau217 and Aß1-42/Aß1-40 ratio) • imaging analysis using volumetric magnetic resonance imaging (vMRI) • alpha/theta ratio of the electroencephalogram (EEG) To evaluate the safety of T 817MA by clinical laboratory tests and AEs. To evaluate the pharmacokinetics of T 817MA in plasma and CSF.;Primary end point(s): The primary efficacy endpoint is the change in the CSF biomarker p-tau181 from Baseline to Week 78.;Timepoint(s) of evaluation of this end point: Baseline, week 52 and week 78. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary efficacy endpoints are: 1. The change in cognitive function assessed by CDR-sb and CFC from Baseline to Weeks 28, 52 and 78. 2. The change in the CSF biomarker p-tau181 from Baseline to Week 52. 3. The change in the CSF biomarkers p-tau217, total tau, Aß1-42, Aß1-40, NFL, neurogranin, YKL-40 and Aß1-42/Aß1-40 ratio from Baseline to Weeks 52 and 78. 4. The change in plasma biomarkers Aß1-42, Aß1-40, NFL, GFAP, p-tau181, p-tau217 and Aß1-42/Aß1-40 ratio from Baseline to Weeks 52 and 78. 5. The change in brain volume (total brain volume (TBV), ventricular volume and hippocampal volume) and cortical thickness measured by vMRI from Baseline to Weeks 52 and 78 6. The change in alpha/theta ratio measured by the EEG from Baseline to Weeks 52 and 78 ;Timepoint(s) of evaluation of this end point: Baseline, week 52 and week 78. | — |
Countries
Czechia, Czech Republic, Germany, Hungary, Ireland, Netherlands, Spain, United Kingdom
Contacts
Public ContactProject Manager
Julius Clinical
Outcome results
None listed