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

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

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:

1. 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)
2. To evaluate the safety of T-817MA by clinical laboratory tests and adverse events (AEs).
3. To evaluate the pharmacokinetics of T-817MA

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: Placebo; Drug: T-817MA

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czechia
  • Brno, Czechia
    • FNUSA - Mezinarodni centrum klinickeho vyzkumu
  • Hradec Králové, Czechia
    • FNHK - Neurologicka klinika
  • Plzen, Czechia
    • A-Shine, s.r.o.
  • Prague, Czechia
    • CLINTRIAL, s.r.o.
  • Rychnov, Czechia
    • VESTRACLINICS, s.r.o.
• Germany
  • Frankfurt, Germany
    • Klinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
  • Kiel, Germany
    • Klinik für Neurologie Universitätsklinikum Schleswig-Holstein
  • Leipzig, Germany
    • Klinik und Poliklinik für Neurologie Universitätsklinikum Leipzig
  • Magdeburg, Germany
    • Universitätsklinikum Magdeburg Institut für Kognitive Neurologie und Demenzforschung
  • Mannheim, Germany
    • Institut für Studien zur Psychischen Gesundheit (ISPG)
  • München, Germany
    • Technische Universität München
  • Münster, Germany
    • Universitätsklinikum Münster Klinik für Allgemeine Neurologie
  • Rostock, Germany
    • Universitätsmedizin Rostock Zentrum für Nervenheilkunde Klinik für Psychosomatik und Psychotherapeutische Medizin
  • Ulm, Germany
    • Universitätsklinikum Ulm Studienzentrum Klinik für Neurologie
• Hungary
  • Budapest, Hungary
    • Debreceni Egyetem KK, Pszichiátriai Klinika
  • Debrecen, Hungary
    • Jávorszky Ödön Városi Kórház, Gyógyszertár
  • Győr, Hungary
    • Semmelweis Egyetem, Pszichiátriai és Pszichoterápiás Klinika
  • Vác, Hungary
    • Semmelweis Egyetem Neurológiai Klinika Gyógyszertára, C földszint
• Ireland
  • Dublin, Ireland
    • St. Vincent's University Hospital
  • Dublin, Ireland
    • Tallaght University Hospital.
• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Brain Research Center Den Bosch
  • Amsterdam, Netherlands
    • Brain Research Center
  • Breda, Netherlands
    • Amphia Ziekenhuis
  • Zwolle, Netherlands
    • Isala Ziekenhuis
• Spain
  • Alicante, Spain
    • Hospital General Universitari d' Elx
  • Barcelona, Spain
    • Fundació ACE
  • Barcelona, Spain
    • Àrea Gestió Documentació Assaigs Clínics-AGDAC Hospital Santa Creu i Sant Pau
  • El Palmar, Spain
    • Hospital Clinico Universitario Virgen de la Arrixaca
  • Getxo, Spain
    • CAE Oroitu
  • Salamanca, Spain
    • Complejo Asistencial Universitario de Salamanca
  • Sevilla, Spain
    • Hospital Victoria Eugenia - Cruz Roja
  • Zaragoza, Spain
    • Hospital Viamed Montecanal
• United Kingdom
  • Bath, United Kingdom
    • University of Bath
  • Bristol, United Kingdom
    • Southmead Hospital North Bristol NHS Trust
  • Glasgow, United Kingdom
    • Glasgow Memory Clinic
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust
  • Southampton, United Kingdom
    • Memory Assessment & Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo once daily
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The change in the CSF p-tau181 from Baseline to Week 78	Baseline to Week 78

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: FUJIFILM Toyama Chemical Co., Ltd.
• Investigators: Study Director: Philip Scheltens, MD, PhD, VUmc Alzheimer Centrum

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2019
• Primary Completion (Actual): February 22, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: December 5, 2019
• First Posted (Actual): December 9, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2023
• Last Update Submitted That Met QC Criteria: October 19, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: T817MAEU201; 2018-003567-66 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Details for sharing data have not been decided yet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No