A study to evaluate the efficacy and safety of T 817MA in patients with mild cognitive impairment due to Alzheimer’s Disease or mild Alzheimer’s Disease.Patients to be randomly allocated to either placebo or investigational drug; assignment will be unknown to patients and doctor.

Phase 1

Conditions: Mild cognitive impairment due to Alzheimer's Disease or mild Alzheimer's Disease.
MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852
MedDRA version: 21.1Level: LLTClassification code 10009846Term: Cognitive impairmentSystem Organ Class: 100000004852
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2018-003567-66-DE

Lead Sponsor: FUJIFILM Toyama Chemical Co., Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

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 10004. A brain MRI not-inconsistent with the clinical diagnosis of MCI due to AD or mild AD
5. Recieving an AChE inhibitor (donepezil, galantamine or rivastigmine) at a stable dose for more than 3 months prior to randomization, or not receiving any AChE inhibitors.
6. Weight of = 100 kg (220 pounds) at Screening
7. Ability (patients and their study partners) to read, speak and understand local language to ensure compliance with cognitive testing and study visit procedures
8. Living in the community (includes assisted living facilities, but excludes long-term care nursing facilities)
9. Ambulatory, or able to walk with an assistive device, such as a cane or walker
10. If male, patients must:
a. agree he will not donate sperm during the study and until 104 days after the last dose, AND
b. be required to use the following highly effective methods of contraception during the study and until 104 days after the last dose:
i. Abstain from sexual intercourse OR
ii. Use a condom during sexual intercourse with pregnant or non-pregnant women of childbearing potential (WOCBP) partner even if he is vasectomized. In addition, WOCBP partner of the male patient (except a vasectomized male) must use one of the following highly effective methods of contraception.
• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- oral
- intravaginal
- transdermal
• Progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
• Intrauterine device (IUD)
• Intrauterine hormone-releasing system (IUS)
• Bilateral tubal occlusion
11. If female, patients must:
a. be post-menopausal (i.e. no menses for 12 months without an alternative medical cause) OR
b. be permanently sterilized with methods including hysterectomy, bilateral salpingectomy and bilateral oophorectomy
12. A study partner who has regular contact with the patient for at least 10 hours per week and is able to participate in the patient’s clinical assessment and complete the questionnaire about the patient’s daily life at Screening, Baseline and Weeks 28, 52 and 78
13. Patient is clearly able to understand the nature, meaning and consequences of the clinical trial and its interventions and conveys his/her will to participate by personally signing the informed consent form
14. Written informed consent obtained from study partner.
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100

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 < 30 ml/min/1.73m2 or CrCl <30 ml/min)
15. Clinically significant B12 deficiency (i.e., no macrocytosis) in the opinion of the investigator
16. Severe heart disease (history of myocardial infarction, congestive heart disease, history of unstable angina pectoris, clinically significant ECG abnormality) within 6 months prior to screening. Patients with arterial thrombosis will not be excluded if they are stable for at least 6 months prior to Screening
17. Cancer or a malignant tumor within the past 3 years, except patients who underwent potentially curative therapy with no evidence of recurrence.
18. Participation in another clinical trial for an investigational agent and having taken at least one dose of study medication, unless confirmed as having been on placebo, within 12 weeks prior to screening. (The end of a previous investigational trial is defined as the date of the last dose of an investigational agent.)
19. Participation in a previous clinical trial with T-817MA
20. Patients whom the investigator deems to be otherwise ineligible
21. Has an MRI of the brain at screening indicative of significant abnormality, including, but not limited to, prior hemorrhage or infarct, large (>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).

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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