Efficacy and Safety of T-817MA in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD

Sponsor

FUJIFILM Toyama Chemical Co., Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04191486

Collaborator

(none)

200

Enrollment

Locations

Arms

38.2

Anticipated Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary objective is to evaluate the neuroprotective effect of T-817MA on Tau protein phosphorylated at threonine 181 (p-tau 181) in cerebrospinal fluid (CSF) compared with placebo in patients with a diagnosis of MCI due to AD or mild AD.

Secondary objectives are:

To evaluate in patients on T-817MA and placebo:

cognitive function measured by the Clinical Dementia Rating Scale Sum of Boxes (CDR-sb) and working memory and attention domain as measured by the Cognitive Functional Composite (CFC).
AD-related biomarkers in CSF and plasma
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 adverse events (AEs).
To evaluate the pharmacokinetics of T-817MA

Condition or Disease	Intervention/Treatment	Phase
Mild Cognitive Impairment	Drug: T-817MA Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group 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

Actual Study Start Date :

Dec 24, 2019

Anticipated Primary Completion Date :

Feb 1, 2023

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: T-817MA (448 mg)	Drug: T-817MA 224mg T-817MA orally once daily for first 4 weeks, and then 448mg T-817MA orally once daily for the following weeks.
Placebo Comparator: Placebo	Drug: Placebo Placebo once daily

Arm

Intervention/Treatment

Experimental: T-817MA (448 mg)

Drug: T-817MA

224mg T-817MA orally once daily for first 4 weeks, and then 448mg T-817MA orally once daily for the following weeks.

Placebo Comparator: Placebo

Drug: Placebo

Placebo once daily

Outcome Measures

Primary Outcome Measures

The change in the CSF p-tau181 from Baseline to Week 78 [Baseline to Week 78]

Secondary Outcome Measures

The change in the CSF p-tau181 from Baseline to Week 52 [Baseline to Week 52]
The change in the CSF p-tau217 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF total tau from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF Aβ1-42 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF Aβ1-40 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF neurofilament light (NFL) from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF neurogranin from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF YKL-40 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the CSF Aβ1-42/Aβ1-40 ratio from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the plasma Aβ1-42 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the plasma Aβ1-40 from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in the plasma NFL from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
The change in cognitive function assessed by CDR-sb and working memory and attention domain as measured by the CFC from Baseline to Weeks 28, 52 and 78 [Baseline to Weeks 28, 52 and 78]
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 [Baseline to Weeks 52 and 78]
The change in alpha/theta ratio measured by the EEG from Baseline to Weeks 52 and 78 [Baseline to Weeks 52 and 78]
Safety as assessed by the occurrence of AEs, clinical laboratory tests, vital signs, physical examinations, ECGs [Screening to Week 82]
Population PK analysis of T-817MA with assessment of maximum plasma concentration (Cmax) [Weeks 16, 28, 40, and 65]
Population PK analysis of T-817MA with assessment of minimum plasma concentration (Cmin) [Weeks 16, 28, 40, and 65]
Population PK analysis of T-817MA with assessment of total daily exposure (AUC0-24h) [Weeks 16, 28, 40, and 65]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Female of non-childbearing potential or male, ages 50 to 80 years (inclusive)
MCI due to AD or mild AD per NIA-AA diagnostic criteria (Jack et al., 2018), with MMSE 24 to 30 (inclusive)
CSF results at Screening consistent with the presence of Aß and p-tau181 abnormality (≤1000 pg/ml for Aß, ≥19 pg/ml for p-tau181).
Taking stable dose of AChE Inhibitor (donepezil, galantamine or rivastigmine) at least for 3 months prior to randomization, or not taking any AChE Inhibitors.

Key Exclusion Criteria:

MRI of the brain within the previous 2 years that showed pathology that would be inconsistent with a diagnosis of AD
Taking memantine
Any contraindications to lumbar puncture
Any contraindications to MRI

Contacts and Locations

Locations

	Site	City	Country
1	FNUSA - Mezinarodni centrum klinickeho vyzkumu	Brno	Czechia
2	FNHK - Neurologicka klinika	Hradec Králové	Czechia
3	A-shine, s.r.o.	Plzen	Czechia
4	CLINTRIAL, s.r.o.	Prague	Czechia
5	VESTRACLINICS, s.r.o.	Rychnov	Czechia
6	Klinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt	Frankfurt	Germany
7	Klinik für Neurologie Universitätsklinikum Schleswig-Holstein	Kiel	Germany
8	Klinik und Poliklinik für Neurologie Universitätsklinikum Leipzig	Leipzig	Germany
9	Universitätsklinikum Magdeburg Institut für Kognitive Neurologie und Demenzforschung	Magdeburg	Germany
10	Institut für Studien zur Psychischen Gesundheit (ISPG)	Mannheim	Germany
11	Technische Universität München	München	Germany
12	Universitätsklinikum Münster Klinik für Allgemeine Neurologie	Münster	Germany
13	Universitätsmedizin Rostock Zentrum für Nervenheilkunde Klinik für Psychosomatik und Psychotherapeutische Medizin	Rostock	Germany
14	Universitätsklinikum Ulm Studienzentrum Klinik für Neurologie	Ulm	Germany
15	Debreceni Egyetem KK, Pszichiátriai Klinika	Budapest	Hungary
16	Jávorszky Ödön Városi Kórház, Gyógyszertár	Debrecen	Hungary
17	Semmelweis Egyetem, Pszichiátriai és Pszichoterápiás Klinika	Győr	Hungary
18	Semmelweis Egyetem Neurológiai Klinika Gyógyszertára, C földszint	Vác	Hungary
19	St. Vincent's University Hospital	Dublin	Ireland
20	Tallaght University Hospital.	Dublin	Ireland
21	Brain Research Center Den Bosch	's-Hertogenbosch	Netherlands
22	Brain Research Center	Amsterdam	Netherlands
23	Amphia ziekenhuis	Breda	Netherlands
24	Isala ziekenhuis	Zwolle	Netherlands
25	Hospital General Universitari d' Elx	Alicante	Spain
26	Fundació ACE	Barcelona	Spain
27	Àrea Gestió Documentació Assaigs Clínics-AGDAC Hospital Santa Creu i Sant Pau	Barcelona	Spain
28	Hospital Clínico Universitario Virgen de La Arrixaca	El Palmar	Spain
29	CAE Oroitu	Getxo	Spain
30	Complejo Asistencial Universitario de Salamanca	Salamanca	Spain
31	Hospital Victoria Eugenia - Cruz Roja	Sevilla	Spain
32	Hospital Viamed Montecanal	Zaragoza	Spain
33	University of Bath	Bath	United Kingdom
34	Southmead Hospital North Bristol NHS Trust	Bristol	United Kingdom
35	Glasgow memory Clinic	Glasgow	United Kingdom
36	Imperial College Healthcare NHS Trust	London	United Kingdom
37	Memory Assessment & Research Centre	Southampton	United Kingdom

Sponsors and Collaborators

FUJIFILM Toyama Chemical Co., Ltd.

Investigators

Study Director: Philip Scheltens, MD, PhD, VUmc Alzheimer Centrum

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

FUJIFILM Toyama Chemical Co., Ltd.

ClinicalTrials.gov Identifier:

NCT04191486

Other Study ID Numbers:

T817MAEU201
2018-003567-66

First Posted:

Dec 9, 2019

Last Update Posted:

Jun 29, 2021

Last Verified:

Jun 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Alzheimer Disease

Cognitive Dysfunction

Study Results

No Results Posted as of Jun 29, 2021