Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
- Conditions
- Behavioral Variant Frontotemporal Dementia (bvFTD)
- Interventions
- Drug: Placebo
- Registration Number
- NCT01626378
- Lead Sponsor
- TauRx Therapeutics Ltd
- Brief Summary
The purpose of this study is to demonstrate the safety and efficacy of TRx0237 in the treatment of patients with behavioral variant frontotemporal dementia (bvFTD).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
- Diagnosis of probable bvFTD
- Centrally rated frontotemporal atrophy score of 2 or greater on brain MRI
- MMSE ≥20
- Age <80 years
- Modified Hachinski ischemic score of ≤ 4
- Females, if of child-bearing potential, must practice true abstinence or be competent to use adequate contraception and agree to maintain this throughout the study
- 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
- Has one (or more) identified adult caregiver who 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; either lives with the subject or sees the subject for ≥2 hours/day ≥3 days/week; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug
- If currently taking an acetylcholinesterase inhibitor and/or memantine, the subject must have been taking such medication(s) for ≥3 months. The dosage regimen must have remained stable for ≥6 weeks and it must be planned to remain stable throughout participation in the study.
- Able to comply with the study procedures
-
Significant central nervous system (CNS) disorder other than bvFTD
-
Significant intracranial pathology seen on brain MRI scan
-
Biomarker evidence of underlying Alzheimer's disease pathology
-
Expressive language deficits
-
Meets research criteria for Amyotrophic Lateral Sclerosis or motor neuron disease
-
Meets diagnostic criteria for probable bvFTD but has a proven mutation producing non-tau, non-TDP-43 pathology
-
Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes
-
Epilepsy
-
Rapid eye movement sleep behavior disorder
-
Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, substance (including alcohol) related disorders
-
Metal implants in the head (except dental), pacemaker, cochlear implants, or any other non-removable items that are contraindications to MRI
-
Resides in hospital or moderate to high dependency continuous care facility
-
History of swallowing difficulties
-
Pregnant or breastfeeding
-
Glucose-6-phosphate dehydrogenase deficiency
-
History of significant hematological abnormality or current acute or chronic clinically significant abnormality
-
Abnormal serum chemistry laboratory value at Screening deemed to be clinically relevant by the investigator
-
Clinically significant cardiovascular disease or abnormal assessments
-
Preexisting or current signs or symptoms of respiratory failure
-
Concurrent acute or chronic clinically significant immunologic, hepatic, or endocrine disease (not adequately treated) and/or other unstable or major disease other than bvFTD
-
Diagnosis of cancer within the past 2 years prior to Baseline (other than basal cell or squamous cell skin cancer or Stage 1 prostate cancer) unless treatment has resulted in complete freedom from disease for at least 2 years
-
Prior intolerance or hypersensitivity to methylthioninium-containing drug, similar organic dyes, or any of the excipients
-
Treatment currently or within 90 days before Baseline with any of the following medications (unless otherwise noted):
- Tacrine
- Amphetamine or dexamphetamine
- Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)
- Carbamazepine, primidone
- Drugs for which there is a warning or precaution in the labeling about methemoglobinemia at approved doses
-
Current or prior participation in a clinical trial as follows:
- Clinical trial of a product for cognition within 3 months of Screening (unless confirmed to have been randomized to placebo)
- A clinical trial of a drug, biologic, device, or medical food in which the last dose/administration was received within 28 days prior to Baseline
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TRx0237 200 mg/day group TRx0237 - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) 52 weeks Change from Baseline on whole brain volume (assessed by brain MRI) 52 weeks Change from Baseline on Functional Activities Questionnaire (FAQ) 52 weeks
- Secondary Outcome Measures
Name Time Method Change from Baseline on Frontotemporal Dementia Rating Scale (FRS) 52 weeks Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) 52 weeks Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes 52 weeks Safety parameters included adverse events, vital signs, methemoglobin and oxygen saturation, physical and neurological examinations, laboratory tests (hematology, serum chemistry, and urinalysis), electrocardiograms, assessment of serotonin syndrome, brain magnetic resonance imaging (MRI) and potential for suicidal behavior and thoughts
Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) 52 weeks
Trial Locations
- Locations (67)
University Hospitals Case Medical Center, Neurology Clinical Trials Unit
🇺🇸Cleveland, Ohio, United States
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
UNC Department of Neurology, Physicians Office Building
🇺🇸Chapel Hill, North Carolina, United States
Neurological Associates of Albany, P. C.
🇺🇸Albany, New York, United States
Mayo Clinic, Department of Neurology
🇺🇸Rochester, Minnesota, United States
David Geffen School of Medicine at UCLA, UCLA Neurological Services
🇺🇸Los Angeles, California, United States
Compass Research, LLC
🇺🇸Orlando, Florida, United States
Alexian Brothers Neurosciences Institute Clinical Research
🇺🇸Elk Grove Village, Illinois, United States
St Margaret's Hospital Mental Health Unit
🇬🇧Epping, United Kingdom
Meridien Research
🇺🇸Brooksville, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Department of Neurology, Emory University
🇺🇸Atlanta, Georgia, United States
Rivers Wellness and Research Institute
🇺🇸Oklahoma City, Oklahoma, United States
Ceuta University Hospital; Neurology
🇪🇸Ceuta, Spain
Hospital of the University of Pennsylvania, Department of Neurology
🇺🇸Philadelphia, Pennsylvania, United States
NHS Grampian, OAP Directorate
🇬🇧Aberdeen, United Kingdom
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Geriatric Clinical Trials Group, Parkwood Institute
🇨🇦London, Ontario, Canada
Memory Clinic, ECRC
🇩🇪Berlin, Germany
Cognition Health Ltd.
🇬🇧London, United Kingdom
NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska
🇵🇱Poznań, Poland
Imperial College Healthcare NHS Trust - Charing Cross Hospital
🇬🇧London, United Kingdom
National Neuroscience Institute Department of Neurology
🇸🇬Singapore, Singapore
The Barberry Out-Patients Department
🇬🇧Birmingham, United Kingdom
2gether NHS foundation trust
🇬🇧Cheltenham, United Kingdom
Kingsway Hospital
🇬🇧Derby, United Kingdom
Dementia Research Center at Queens Square
🇬🇧London, United Kingdom
Neurodegenerative Disorders Research Pty Ltd
🇦🇺West Perth, Western Australia, Australia
Unità di Neuroimmagine e Epidemiologia Alzheimer
🇮🇹Brescia, Italy
Fondazione Universita' Gabriele D'Annunzio di Chieti
🇮🇹Chieti Scalo, Italy
Fondazione IRCCS Istituto Neurologico "Carlo Besta"
🇮🇹Milano, Italy
Neurology I, Department of Neuroscience, University of Torino
🇮🇹Torino, Italy
The Shankle Clinic
🇺🇸Newport Beach, California, United States
Memory and Aging Centre
🇺🇸San Francisco, California, United States
Johns Hopkins University
🇺🇸Baltimore, Maryland, United States
Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Heritage Medical Research Clinic-University of Calgary
🇨🇦Calgary, Alberta, Canada
Nuffield Department of Clinical Neurosciences
🇬🇧Oxford, United Kingdom
Redwoods Centre
🇬🇧Shrewsbury, United Kingdom
Wessex Neurological Centre, Southampton General Hospital
🇬🇧Southampton, United Kingdom
University Hospital Centre Zagreb
🇭🇷Zagreb, Croatia
Psychomedical Consult
🇷🇴Bucharest, Romania
Mayo Clinic
🇺🇸Jacksonville, Florida, United States
Alzheimer Research Center Amsterdam
🇳🇱Amsterdam, Netherlands
University Psychiatric Hospital Vrapče
🇭🇷Zagreb, Croatia
Euromedis Sp. z o.o.
🇵🇱Szczecin, Poland
Vancouver Island Health Authority
🇨🇦Victoria, British Columbia, Canada
True North Clinical Research
🇨🇦Halifax, Nova Scotia, Canada
University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
🇨🇦Vancouver, British Columbia, Canada
Erasmus University Medical Center
🇳🇱Rotterdam, Netherlands
The Memory Clinic
🇺🇸Bennington, Vermont, United States
McGill Centre for Studies in Aging, Alzheimer Disease Research Unit
🇨🇦Verdun, Quebec, Canada
Jeroen Bosch Ziekenhuis, afdeling geriatrie
🇳🇱Den Bosch, Netherlands
Hospital Viamed Montecanal, Neurology Department
🇪🇸Zaragoza, Spain
Fundació ACE. Institut Català de Neurociències Aplicades
🇪🇸Barcelona, Spain
Universitäts - und Rehabilitationskliniken Ulm, Neurologie
🇩🇪Ulm, Germany
Integrative Clinical Trials LLC
🇺🇸Brooklyn, New York, United States
PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic
🇺🇸Salt Lake City, Utah, United States
University Health Network, Toronto Western Hospital, Memory Clinic
🇨🇦Toronto, Ontario, Canada
Charité-Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie
🇩🇪Berlin, Germany
Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München
🇩🇪München, Germany
Universitätsklinikum Hamburg-Eppendorf Klinik für Psychiatrie und Psychotherapie
🇩🇪Hamburg, Germany
Indiana University Department of Neurology
🇺🇸Indianapolis, Indiana, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
The Clinical Trial Center, LLC
🇺🇸Jenkintown, Pennsylvania, United States
Neuroscience Research Australia
🇦🇺Randwick, New South Wales, Australia