Clinical trial NCT01626378: Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
Official title: A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Behavioral Variant Frontotemporal Dementia (bvFTD)
Keywords: Behavioral Variant Frontotemporal Dementia
bvFTD
Frontotemporal Dementia
Lead sponsor: TauRx Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2012-06-22
Enrollment: 220
Sex: ALL
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R)
timeFrame: 52 weeks
measure: Change from Baseline on Functional Activities Questionnaire (FAQ)
timeFrame: 52 weeks
measure: Change from Baseline on whole brain volume (assessed by brain MRI)
timeFrame: 52 weeks
Secondary outcomes:
measure: Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III)
timeFrame: 52 weeks
measure: Change from Baseline on Frontotemporal Dementia Rating Scale (FRS)
timeFrame: 52 weeks
measure: Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC)
timeFrame: 52 weeks
measure: Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes
timeFrame: 52 weeks
Other outcomes:
measure: Early effect on modified ADCS-CGIC (change from Baseline)
timeFrame: 8 weeks
measure: Change from Baseline on the rate of atrophy in frontal and temporal lobes as well as ventricular volume (assessed by brain MRI)
timeFrame: 52 weeks
measure: Change from Baseline on Mini-Mental Status Examination (MMSE)
timeFrame: 52 weeks
measure: Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III)
timeFrame: 52 weeks
measure: Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD
timeFrame: 52 weeks
Locations:
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA, UCLA Neurological Services
state: California
city: Newport Beach
country: United States
facility: The Shankle Clinic
state: California
city: San Francisco
country: United States
facility: Memory and Aging Centre
state: California
city: Brooksville
country: United States
facility: Meridien Research
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Department of Neurology, Emory University
state: Georgia
city: Elk Grove Village
country: United States
facility: Alexian Brothers Neurosciences Institute Clinical Research
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Department of Neurology
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic, Department of Neurology
state: Minnesota
city: Eatontown
country: United States
facility: Memory Enhancement Center of America, Inc.
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, P. C.
state: New York
city: Brooklyn
country: United States
facility: Integrative Clinical Trials LLC
state: New York
city: Chapel Hill
country: United States
facility: UNC Department of Neurology, Physicians Office Building
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center, Neurology Clinical Trials Unit
state: Ohio
city: Oklahoma City
country: United States
facility: Rivers Wellness and Research Institute
state: Oklahoma
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania, Department of Neurology
state: Pennsylvania
city: Salt Lake City
country: United States
facility: PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic
state: Utah
city: Bennington
country: United States
facility: The Memory Clinic
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Randwick
country: Australia
facility: Neuroscience Research Australia
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: West Perth
country: Australia
facility: Neurodegenerative Disorders Research Pty Ltd
state: Western Australia
city: Calgary
country: Canada
facility: Heritage Medical Research Clinic-University of Calgary
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders
state: British Columbia
city: Victoria
country: Canada
facility: Vancouver Island Health Authority
state: British Columbia
city: Halifax
country: Canada
facility: True North Clinical Research
state: Nova Scotia
city: London
country: Canada
facility: Geriatric Clinical Trials Group, Parkwood Institute
state: Ontario
city: Toronto
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Toronto
country: Canada
facility: University Health Network, Toronto Western Hospital, Memory Clinic
state: Ontario
city: Verdun
country: Canada
facility: McGill Centre for Studies in Aging, Alzheimer Disease Research Unit
state: Quebec
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: University Psychiatric Hospital Vrapče
city: Berlin
country: Germany
facility: Charité-Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie
city: Berlin
country: Germany
facility: Memory Clinic, ECRC
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf Klinik für Psychiatrie und Psychotherapie
city: München
country: Germany
facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München
city: Ulm
country: Germany
facility: Universitäts - und Rehabilitationskliniken Ulm, Neurologie
city: Brescia
country: Italy
facility: Unità di Neuroimmagine e Epidemiologia Alzheimer
city: Chieti Scalo
country: Italy
facility: Fondazione Universita' Gabriele D'Annunzio di Chieti
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Neurologico "Carlo Besta"
city: Torino
country: Italy
facility: Neurology I, Department of Neuroscience, University of Torino
city: Amsterdam
country: Netherlands
facility: Alzheimer Research Center Amsterdam
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis, afdeling geriatrie
city: Rotterdam
country: Netherlands
facility: Erasmus University Medical Center
city: Poznań
country: Poland
facility: NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska
city: Szczecin
country: Poland
facility: Euromedis Sp. z o.o.
city: Bucharest
country: Romania
facility: Psychomedical Consult
city: Singapore
country: Singapore
facility: National Neuroscience Institute Department of Neurology
city: Barcelona
country: Spain
facility: Fundació ACE. Institut Català de Neurociències Aplicades
city: Ceuta
country: Spain
facility: Ceuta University Hospital; Neurology
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal, Neurology Department
city: Aberdeen
country: United Kingdom
facility: NHS Grampian, OAP Directorate
city: Birmingham
country: United Kingdom
facility: The Barberry Out-Patients Department
city: Cheltenham
country: United Kingdom
facility: 2gether NHS foundation trust
city: Derby
country: United Kingdom
facility: Kingsway Hospital
city: Epping
country: United Kingdom
facility: St Margaret's Hospital Mental Health Unit
city: London
country: United Kingdom
facility: Cognition Health Ltd.
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust - Charing Cross Hospital
city: London
country: United Kingdom
facility: Dementia Research Center at Queens Square
city: Oxford
country: United Kingdom
facility: Nuffield Department of Clinical Neurosciences
city: Shrewsbury
country: United Kingdom
facility: Redwoods Centre
city: Southampton
country: United Kingdom
facility: Wessex Neurological Centre, Southampton General Hospital
Study officials:
References:
citation: Pletnikova O, Sloane KL, Renton AE, Traynor BJ, Crain BJ, Reid T, Zu T, Ranum LP, Troncoso JC, Rabins PV, Onyike CU. Hippocampal sclerosis dementia with the C9ORF72 hexanucleotide repeat expansion. Neurobiol Aging. 2014 Oct;35(10):2419.e17-21. doi: 10.1016/j.neurobiolaging.2014.04.009. Epub 2014 Apr 18.