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

NCT04191486 | Completed Phase 2 DMC

• 2 other identifiers: T817MAEU2012018-003567-66
• Study Type: interventional
• Target: 221
• Locations: 7 countries
• Sites: 37

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:

• 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

Conditions

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

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

  Baseline to Week 78

Secondary Outcomes (19)

• 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

Study Arms (2)

T-817MA (448 mg)

EXPERIMENTAL

Drug: T-817MA

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

T-817MA DRUG

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

T-817MA (448 mg)

Placebo DRUG

Placebo once daily

Placebo

Eligibility Criteria

• Age: 50 Years - 80 Years
• Gender Eligibility Details: If male, patients must: 1. agree he will not donate sperm during the study and until 104 days after the last dose, AND 2. be required to use highly effective methods of contraception during the study and until 104 days after the last dose If female, patients must: 1. be post-menopausal (i.e. no menses for 12 months without an alternative medical cause) OR 2. be permanently sterilized with methods including hysterectomy, bilateral salpingectomy and bilateral oophorectomy
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• FUJIFILM Toyama Chemical Co., Ltd.: lead

Study Sites (37)

FNUSA - Mezinarodni centrum klinickeho vyzkumu

Brno, Czechia

Location

FNHK - Neurologicka klinika

Hradec Králové, Czechia

Location

A-shine, s.r.o.

Pilsen, Czechia

Location

CLINTRIAL, s.r.o.

Prague, Czechia

Location

VESTRACLINICS, s.r.o.

Rychnov, Czechia

Location

Klinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt

Frankfurt, Germany

Location

Klinik für Neurologie Universitätsklinikum Schleswig-Holstein

Kiel, Germany

Location

Klinik und Poliklinik für Neurologie Universitätsklinikum Leipzig

Leipzig, Germany

Location

Universitätsklinikum Magdeburg Institut für Kognitive Neurologie und Demenzforschung

Magdeburg, Germany

Location

Institut für Studien zur Psychischen Gesundheit (ISPG)

Mannheim, Germany

Location

Technische Universität München

München, Germany

Location

Universitätsklinikum Münster Klinik für Allgemeine Neurologie

Münster, Germany

Location

Universitätsmedizin Rostock Zentrum für Nervenheilkunde Klinik für Psychosomatik und Psychotherapeutische Medizin

Rostock, Germany

Location

Universitätsklinikum Ulm Studienzentrum Klinik für Neurologie

Ulm, Germany

Location

Debreceni Egyetem KK, Pszichiátriai Klinika

Budapest, Hungary

Location

Jávorszky Ödön Városi Kórház, Gyógyszertár

Debrecen, Hungary

Location

Semmelweis Egyetem, Pszichiátriai és Pszichoterápiás Klinika

Győr, Hungary

Location

Semmelweis Egyetem Neurológiai Klinika Gyógyszertára, C földszint

Vác, Hungary

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

Tallaght University Hospital.

Dublin, Ireland

Location

Brain Research Center Den Bosch

's-Hertogenbosch, Netherlands

Location

Brain Research Center

Amsterdam, Netherlands

Location

Amphia ziekenhuis

Breda, Netherlands

Location

Isala ziekenhuis

Zwolle, Netherlands

Location

Hospital General Universitari d' Elx

Alicante, Spain

Location

Fundació ACE

Barcelona, Spain

Location

Àrea Gestió Documentació Assaigs Clínics-AGDAC Hospital Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital Clínico Universitario Virgen de La Arrixaca

El Palmar, Spain

Location

CAE Oroitu

Getxo, Spain

Location

Complejo Asistencial Universitario de Salamanca

Salamanca, Spain

Location

Hospital Victoria Eugenia - Cruz Roja

Seville, Spain

Location

Hospital Viamed Montecanal

Zaragoza, Spain

Location

University of Bath

Bath, United Kingdom

Location

Southmead Hospital North Bristol NHS Trust

Bristol, United Kingdom

Location

Glasgow memory Clinic

Glasgow, United Kingdom

Location

Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Memory Assessment & Research Centre

Southampton, United Kingdom

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

1-(3-(2-(1-benzothiophen-5-yl) ethoxy) propyl)-3-azetidinol maleate

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Philip Scheltens, MD, PhD

  VUmc Alzheimer Centrum

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2019
• First Posted: December 9, 2019
• Study Start: December 24, 2019
• Primary Completion: February 22, 2023
• Study Completion: March 20, 2023
• Last Updated: October 23, 2023

Record last verified: 2023-02

Locations

HU (4); IE (2); CZ (5); DE (9); NL (4); GB (5); ES (8)