Clinical trial NCT04191486: Efficacy and Safety of T-817MA in Patients With Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild AD
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Mild Cognitive Impairment
Lead sponsor: FUJIFILM Toyama Chemical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-12-09
Enrollment: 221
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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


Eligibility criteria: 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

Primary outcomes:
measure: The change in the CSF p-tau181 from Baseline to Week 78
timeFrame: Baseline to Week 78
Secondary outcomes:
measure: The change in the CSF p-tau181 from Baseline to Week 52
timeFrame: Baseline to Week 52
measure: The change in the CSF p-tau217 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF total tau from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF Aβ1-42 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF Aβ1-40 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF neurofilament light (NFL) from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF neurogranin from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF YKL-40 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the CSF Aβ1-42/Aβ1-40 ratio from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the plasma Aβ1-42 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the plasma Aβ1-40 from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: The change in the plasma NFL from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: 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
timeFrame: Baseline to Weeks 28, 52 and 78
measure: 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
timeFrame: Baseline to Weeks 52 and 78
measure: The change in alpha/theta ratio measured by the EEG from Baseline to Weeks 52 and 78
timeFrame: Baseline to Weeks 52 and 78
measure: Safety as assessed by the occurrence of AEs, clinical laboratory tests, vital signs, physical examinations, ECGs
timeFrame: Screening to Week 82
measure: Population PK analysis of T-817MA with assessment of maximum plasma concentration (Cmax)
timeFrame: Weeks 16, 28, 40, and 65
measure: Population PK analysis of T-817MA with assessment of minimum plasma concentration (Cmin)
timeFrame: Weeks 16, 28, 40, and 65
measure: Population PK analysis of T-817MA with assessment of total daily exposure (AUC0-24h)
timeFrame: Weeks 16, 28, 40, and 65
Other outcomes:
Locations:
city: Brno
country: Czechia
facility: FNUSA - Mezinarodni centrum klinickeho vyzkumu
city: Hradec Králové
country: Czechia
facility: FNHK - Neurologicka klinika
city: Plzen
country: Czechia
facility: A-shine, s.r.o.
city: Prague
country: Czechia
facility: CLINTRIAL, s.r.o.
city: Rychnov
country: Czechia
facility: VESTRACLINICS, s.r.o.
city: Frankfurt
country: Germany
facility: Klinik für Psychiatrie, Psychosomatik und Psychotherapie Universitätsklinikum Frankfurt
city: Kiel
country: Germany
facility: Klinik für Neurologie Universitätsklinikum Schleswig-Holstein
city: Leipzig
country: Germany
facility: Klinik und Poliklinik für Neurologie Universitätsklinikum Leipzig
city: Magdeburg
country: Germany
facility: Universitätsklinikum Magdeburg Institut für Kognitive Neurologie und Demenzforschung
city: Mannheim
country: Germany
facility: Institut für Studien zur Psychischen Gesundheit (ISPG)
city: München
country: Germany
facility: Technische Universität München
city: Münster
country: Germany
facility: Universitätsklinikum Münster Klinik für Allgemeine Neurologie
city: Rostock
country: Germany
facility: Universitätsmedizin Rostock Zentrum für Nervenheilkunde Klinik für Psychosomatik und Psychotherapeutische Medizin
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm Studienzentrum Klinik für Neurologie
city: Budapest
country: Hungary
facility: Debreceni Egyetem KK, Pszichiátriai Klinika
city: Debrecen
country: Hungary
facility: Jávorszky Ödön Városi Kórház, Gyógyszertár
city: Győr
country: Hungary
facility: Semmelweis Egyetem, Pszichiátriai és Pszichoterápiás Klinika
city: Vác
country: Hungary
facility: Semmelweis Egyetem Neurológiai Klinika Gyógyszertára, C földszint
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Dublin
country: Ireland
facility: Tallaght University Hospital.
city: 's-Hertogenbosch
country: Netherlands
facility: Brain Research Center Den Bosch
city: Amsterdam
country: Netherlands
facility: Brain Research Center
city: Breda
country: Netherlands
facility: Amphia ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala ziekenhuis
city: Alicante
country: Spain
facility: Hospital General Universitari d' Elx
city: Barcelona
country: Spain
facility: Fundació ACE
city: Barcelona
country: Spain
facility: Àrea Gestió Documentació Assaigs Clínics-AGDAC Hospital Santa Creu i Sant Pau
city: El Palmar
country: Spain
facility: Hospital Clínico Universitario Virgen de La Arrixaca
city: Getxo
country: Spain
facility: CAE Oroitu
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Victoria Eugenia - Cruz Roja
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal
city: Bath
country: United Kingdom
facility: University of Bath
city: Bristol
country: United Kingdom
facility: Southmead Hospital North Bristol NHS Trust
city: Glasgow
country: United Kingdom
facility: Glasgow memory Clinic
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: Southampton
country: United Kingdom
facility: Memory Assessment & Research Centre
Study officials:
affiliation: VUmc Alzheimer Centrum
name: Philip Scheltens, MD, PhD
role: STUDY_DIRECTOR
References: