behavioral variant Frontotemporal Dementia (bvFTD) MedDRA version: 18.1 Level: PT Classification code 10068968 Term: Frontotemporal dementia System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Leuco-methylthioninium bis(hydromethanesulfonate)
Product Code: LMTM/TRx0237
Pharmaceutical Form: Tablet
INN or Proposed INN: N/A
CAS Number: 1236208-20-0
Current Sponsor code: TRx0237
O
Sponsors
TauRx Therapeutics Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of probable bvFTD according to the International Consensus Criteria for bvFTD 2. Centrally rated frontotemporal atrophy score of 2 or greater, taken as the maximum of right or left frontal or anterior temporal lobes on brain MRI of sufficient quality obtained at Screening or within a maximum of 42 days before Baseline, irrespective of pre-existing structural or functional imaging evidence supporting a diagnosis of bvFTD 3. MMSE =20 at the Screening visit 4. Age <80 years at the Screening visit 5. Modified Hachinski ischemic score of =4 at the Screening visit 6. Females must meet one of the following: • Surgically sterile (hysterectomy, bilateral salpingectomy / oophorectomy) for at least 6 months minimum • Have undergone bilateral tubal occlusion / ligation at least 6 months prior • Post-menopausal for at least 1 year • Using adequate contraception (a barrier method [such as condom,diaphragm, or cervical/vault cap] with spermicidal foam, gel, film, cream, or suppository; intrauterine device [IUD] or system, or oral or long-acting injected or implanted hormonal contraceptives for at least 3 months prior to Baseline; or vasectomized partner [with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate]), or true abstinence (when this is in line with the preferred and usual lifestyle of the subject); subjects must be competent to use adequate contraception and to agree to continue to maintain adequate contraception throughout participation in the study OR In Italy, have avoided a pregnancy for at least 3 months prior to Baseline and accept to avoid a pregnancy throughout participation in the study 7. Subject and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with national law is/are able to read, understand, and provide written informed consent in the designated language of the study site 8. Has one or more identified adult caregivers who meet the following criteria: • Either lives with the subject or sees the subject on average for = 2 hours/day = 3 days/week, or in the investigator's opinion, the extent of contact is sufficient to provide meaningful assessment of changes in subject behavior and function over time and provide information on safety and tolerability • Is willing to provide written informed consent for his/her own participation • Is able to read, understand, and speak the designated language at the study site • Agrees to accompany the subject to each study visit • Is able to verify daily compliance with study drug 9. If currently taking an AChEI (i.e., donepezil, galantamine, or rivastigmine) and/or memantine, at the time of Screening: • The subject must have been taking such medication(s) for = 3 months • The current dosage regimen and dosage form must be within the locally approved dose range and must have remained stable for = 6 weeks • It must be planned that the dosage regimen will remain stable throughout participation in the study Subjects not being treated with an AChEI or memantine (for = 6 weeks before Screening) may also be enrolled if initiation of an AChEI or memantine is not planned for the time period during which the subject will be participating in this study 10. Able to comply with the study procedures in the view of the Investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age
Exclusion criteria
Exclusion criteria: 1.Significant CNS disorder other than bvFTD 2.Other significant intracranial pathology seen on brain MRI scan that would lead to a diagnosis other than probable bvFTD or that puts the subject at risk of Amyloid Related Imaging Abnormalities 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.Biomarker evidence of underlying AD pathology as etiology of dementia 4.Expressive language deficits such that the subject is too severely impaired to allow testing at Baseline 5.Meets research criteria for Amyotrophic Lateral Sclerosis or motor;evidence of mild motor neuron disease on examination is allowed if not expected to interfere with subject's completion of study but prominent bulbar symptoms would be exclusionary 6.Meets diagnostic criteria for probable bvFTD but has a proven mutation producing non-tau,non-TDP-43 pathology 7.Clinical evidence or history of: ·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) 8.Epilepsy (a single prior seizure is considered acceptable) 9.Rapid eye movement sleep behavior disorder 10.DSM IV-TR criteria met for the following within specified period: ·Major depressive disorder (current) ·Schizophrenia (lifetime) ·Other psychotic disorders, bipolar disorder (within the past 5 years),or substance related disorders (within the past 2 years) 11.Metal implants in the head (except dental),pacemaker, any other non-removable items that are contraindications to MR imaging; any device proven to be MR compatible will be allowed 12.Resides in hospital or moderate to high dependency continuous care facility 13.History of swallowing difficulties 14.Pregnant or breastfeeding 15.G6PD deficiency 16.History of significant hematological abnormality or current acute or chronic clinically significant abnormality, including: ·Hereditary or acquired methemoglobinemia or Baseline measurement of MetHb >2.0% ·Hemoglobinopathy, myelodysplastic syndrome, hemolytic anemia,or splenectomy ·Screening value below normal range for hemoglobin and vitamin B12 or folate 17.Abnormal serum chemistry laboratory value at Screening clinically relevant.In addition, subjects with 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 ·Hypotension ·Heart rate 96 bpm by measurement of vital signs or by ECG at Screening 19.Preexisting or current signs or symptoms of respiratory failure. Subject
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the efficacy of LMTM as assessed by the change from Baseline on: • Addenbrooke’s Cognitive Examination-Revised (ACE-R) • Symptomatic effect as reflected by the Functional Activities Questionnaire (FAQ) • Disease-modifying effect based on reduction in decline in whole brain volume (WBV), using change from Baseline as measured by the Brain Boundary Shift Integral (BBSI) by MRI imaging ;Secondary Objective: - To evaluate the effect of LMTM as measured by the following additional global, disease severity, and motor impairment scales: • Modified Alzheimer’s Disease Cooperative Study – Clinical Global Impression of Change (Modified ADCS-CGIC) – independently rated • Frontotemporal Dementia Rating Scale (FRS) • Unified Parkinson’s Disease Rating Scale (UPDRS Parts II and III) - To evaluate the safety and tolerability of LMTM;Primary end point(s): Primary Efficacy endpoints: • Change from Baseline to Week 52 in the ACE-R • Either of two co-primary endpoints: o Change from Baseline to Week 52 in FAQ o Reduction in decline in whole brain volume at Week 52 using change from Baseline as measured by the Brain Boundary Shift Integral (BBSI) by MRI imaging ;Timepoint(s) of evaluation of this end point: Efficacy will be evaluated at baseline and after 4 months (16 weeks), 8 months (32 weeks), and 12 months (52 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary clinical endpoints include the following: • Modified CGIC • FRS • UPDRS Parts II and III ;Timepoint(s) of evaluation of this end point: Safety assessment will performed during screening, then at Baseline (pre-dose and post-dose during the 4-hour observation), and 4,8,16,24,32,42 and 52 weeks after Baseline, and approximately 4 weeks after the last dose of study drug (if applicable) Blood will be collected at Baseline and as possible at each subsequent on-treatment visit through Week 52 for purposes of population pharmacokinetic (PK) analysis of MT concentrations A single blood sample for genotyping may be collected any time after eligibility for randomization and participation in the study has been confirmed at Baseline (Visit 2). | — |
Countries
Australia, Canada, Croatia, Finland, Germany, Italy, Netherlands, Poland, Romania, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactInformation Desk
TauRx Therapeutics Ltd
Outcome results
None listed