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

Mild Cognitive Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04191486
• Other study ID #: T817MAEU201
• Secondary ID: 2018-003567-66
• Status: Completed
• Phase: Phase 2
• Start date: December 24, 2019
• Est. completion date: March 20, 2023

Study information

• Verified date: February 2023
• Source: FUJIFILM Toyama Chemical Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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: 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 221
• Est. completion date: March 20, 2023
• Est. primary completion date: February 22, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

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
Placebo once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
FUJIFILM Toyama Chemical Co., Ltd.

Countries where clinical trial is conducted

Czechia,  Germany,  Hungary,  Ireland,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change in the CSF p-tau181 from Baseline to Week 78		Baseline to Week 78
Secondary	The change in the CSF p-tau181 from Baseline to Week 52		Baseline to Week 52
Secondary	The change in the CSF p-tau217 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF total tau from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF Aß1-42 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF Aß1-40 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF neurofilament light (NFL) from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF neurogranin from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF YKL-40 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the CSF Aß1-42/Aß1-40 ratio from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the plasma Aß1-42 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the plasma Aß1-40 from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	The change in the plasma NFL from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	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
Secondary	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
Secondary	The change in alpha/theta ratio measured by the EEG from Baseline to Weeks 52 and 78		Baseline to Weeks 52 and 78
Secondary	Safety as assessed by the occurrence of AEs, clinical laboratory tests, vital signs, physical examinations, ECGs		Screening to Week 82
Secondary	Population PK analysis of T-817MA with assessment of maximum plasma concentration (Cmax)		Weeks 16, 28, 40, and 65
Secondary	Population PK analysis of T-817MA with assessment of minimum plasma concentration (Cmin)		Weeks 16, 28, 40, and 65
Secondary	Population PK analysis of T-817MA with assessment of total daily exposure (AUC0-24h)		Weeks 16, 28, 40, and 65