Alzheimer’s Disease MedDRA version: 16.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: Leuco-methylthioninium bis(hydromethanesulfonate)
Product Code: TRx0237 (LMTM)
Pharmaceutical Form: Tablet
INN or Proposed INN: Not yet established
CAS Number: 1236208-20-0
Current Spons
Sponsors
TauRx Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis according to the National Institute on Aging (NIA) and Alzheimer’s Association (AA) criteria of: • All cause dementia and • Probable Alzheimer’s disease 2. Clinical Dementia Rating (CDR) total score of 1 (mild) and MMSE score of 20-26 (inclusive) at Screening 3. Age =65 years) yes F.1.3.1 Number of subjects for this age range 380
Exclusion criteria
Exclusion criteria: 1.Significant CNS disorder other than AD 2.Significant intracranial focal or vascular pathology seen on brain MRI scan within a maximum of 42 days before Baseline that would lead to a diagnosis other than probable AD or that puts the subject at risk of ARIA, including: large confluent white matter hyperintense lesions, other focal brain lesion(s), a single area of superficial siderosis, >4 cerebral microhemorrhages, evidence of a prior macrohemorrhage 3.Clinical evidence or history of any of the following within specified period prior to Baseline: •Cerebrovascular accident (2 years) •Transient ischemic attack(6 months) •Significant head injury with associated loss of consciousness, skull fracture or persisting cognitive impairment (2 years) •Other unexplained or recurrent loss of consciousness =15 minutes (2 years) 4.Epilepsy (a single prior seizure is considered acceptable) 5.DSM IV-TR criteria met for any of the following within specified period: •Major depressive disorder (current) •Schizophrenia (lifetime) •Other psychotic disorders, bipolar disorder (within the past 5 years), or substance (including alcohol) related disorders (within the past 2 years) 6.Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MR imaging; MR compatible prosthetics, clips, stents, or any other device proven to be compatible will be allowed. 7.Resides in hospital or moderate to high dependency continuous care facility 8.History of swallowing difficulties 9.Pregnant or breastfeeding 10.G6PD deficiency 11.History of significant hematological abnormality or current acute or chronic clinically significant abnormality, including: •History of hereditary or acquired methemoglobinemia or baseline measurement of MetHb >2.0% •History of hemoglobinopathy, myelodysplastic syndrome, hemolytic anemia, or splenectomy •Screening hemoglobin value below age/sex appropriate lower limit of the central laboratory normal range 12.Abnormal serum chemistry laboratory value at Screening. In addition, subjects with either of the following abnormalities must be excluded: creatinine clearance 460 msec in males or >470 msec in females, or low or flat T waves making measurement of QT interval unreliable •Recent history of poorly controlled hypertension, systolic blood pressure >160 mmHg, or diastolic blood pressure >100 mmHg, at Screening •Hypotension: systolic blood pressure 96 bpm by measurement of vital signs or by ECG at Screening 14.Preexisting or current signs or symptoms of respiratory failure. Subjects with previously diagnosed moderate to severe sleep apnea not adequately controlled should be excluded. 15.Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To demonstrate the clinical efficacy of leuco-methylthioninium bis(hydromethanesulfonate) (also known as LMTM, TRx0237) in mild Alzheimer's disease based on change from baseline on the following coprimary endpoints: • Alzheimer's Disease Assessment Scale – Cognitive Subscale (ADAScog11) • Alzheimer's Disease Cooperative Study – Clinical Global Impression of Change (ADCS-CGIC) - independently rated 2. To further demonstrate disease modification based on the following primary endpoint: • reduction in decline in glucose uptake in the temporal lobe on 18Fflurodeoxyglucose positron emission tomography (FDG-PET) imaging 3. To assess the safety and tolerability of LMTM 200 mg/day given for up to 78 weeks;Secondary Objective: Secondary: 1. To evaluate the effect of LMTM on functional activities of daily living using the ADCS-ADL23 2. To evaluate the effects of LMTM on other aspects of Alzheimer’s disease including cognition (Mini-Mental Status Examination, MMSE), behavior (Neuropsychiatric Inventory, NPI), and mood (Montgomery-Asberg Depression Rating Scale, MADRS) Exploratory: 1. To determine the effects of LMTM on Alzheimer’s disease modification by showing retardation of the expected decline in whole brain volume as evaluated by brain magnetic resonance imaging (MRI) 2. To determine the effects of LMTM on resource utilization using the Resource Utilization in Dementia (RUD) Lite 3. To explore changes in certain cerebrospinal fluid (CSF) biomarkers of alzheimer's disease (total tau, phospho-tau and Aß1-42) in subjects who separately consent to lumbar puncture 4. To explore the influence of the Apolipoprotein E genotype on the primary and selected secondary outcomes ;Primary end point(s): Primary efficacy endpoints: ADAS-cog11, ADCS-CGIC.;Timepoint(s) of evaluation of this end point: Assessments will be made at Baseline (Visit 2, pre-dose) and after 13, 26, 39, 52, 65, and 78 weeks, and at the 4-week off-treatment follow-up visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints: ADCS-ADL23, NPI, MADRS, MMSE, FDG-PET and brain MRI, CDR Secondary safety and tolerability endpoints: adverse events (AEs), vital sign and methemoglobin measurements, 12-lead ECGs, clinical laboratory findings, physical and neurological examinations, potential for serotonin toxicity, brain MRI, and potential for suicide or self-harm Other endpoints: RUD Lite questionnaire, blood samples for PK and genotyping, cerebrospinal fluid samples;Timepoint(s) of evaluation of this end point: •ADCS-ADL23: at Baseline, at Weeks 13, 26, 39, 52, 65 and 78, at follow-up visit •MMSE: at Screening, at Weeks 26, 52 and 78, at follow-up visit •FDG-PET: at Screening/Baseline, at Weeks 39 and 78 •Brain MRI: at Screening, at Weeks 13, 26, 39, 52, 65, and 78 •CDR: at Screening •AEs: from the ICF signature and throughout the study •CSSR-S: at Baseline (+prior clinic discharge), at each visit •RUD Lite questionnaire: at Baseline, at Weeks 26, 52 and 78 •Cerebrospinal fluid samples: at Baseline (prior to dosing), at Week 78 •At screening and at each visit: oral T°, respiratory rate, ECG, blood pressure and pulse (+within 1 hour before and approx. 2 hours after first dose), MetHB (+approx. 1 hour before and approx. 2.5 hours after first dose), potential for serotonin toxicity | — |
Countries
Belgium, Croatia, Finland, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactInformation Desk
TauRx Therapeutics Ltd
Outcome results
None listed