Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)

Behavioral Variant Frontotemporal Dementia (bvFTD) Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01626378
• Other study ID #: TRx-237-007
• Status: Completed
• Phase: Phase 3
• First received: June 20, 2012
• Last updated: March 12, 2018
• Start date: May 2013
• Est. completion date: February 2016

Study information

• Verified date: March 2018
• Source: TauRx Therapeutics Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: February 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Aphasia, Primary Progressive
• Behavioral Variant Frontotemporal Dementia (bvFTD)
• Dementia
• Frontotemporal Dementia
• Pick Disease of the Brain

Intervention

Drug:
• TRx0237
TRx0237 100 mg tablet will be administered twice daily.
• Placebo
Placebo tablets will be administered twice daily. The placebo tablets include 4 mg of TRx0237 as a urinary and fecal colorant to maintain blinding; hence, the placebo group will receive a total of 8 mg/day of TRx0237.

Locations

Country	Name	City	State
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Neuroscience Research Australia	Randwick	New South Wales
Australia	Neurodegenerative Disorders Research Pty Ltd	West Perth	Western Australia
Canada	Heritage Medical Research Clinic-University of Calgary	Calgary	Alberta
Canada	True North Clinical Research	Halifax	Nova Scotia
Canada	Geriatric Clinical Trials Group, Parkwood Institute	London	Ontario
Canada	Toronto Memory Program	Toronto	Ontario
Canada	University Health Network, Toronto Western Hospital, Memory Clinic	Toronto	Ontario
Canada	University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders	Vancouver	British Columbia
Canada	McGill Centre for Studies in Aging, Alzheimer Disease Research Unit	Verdun	Quebec
Canada	Vancouver Island Health Authority	Victoria	British Columbia
Croatia	University Hospital Centre Zagreb	Zagreb
Croatia	University Psychiatric Hospital Vrapce	Zagreb
Germany	Charité-Universitätsmedizin Berlin Klinik für Psychiatrie und Psychotherapie	Berlin
Germany	Memory Clinic, ECRC	Berlin
Germany	Universitätsklinikum Hamburg-Eppendorf Klinik für Psychiatrie und Psychotherapie	Hamburg
Germany	Klinik und Poliklinik für Psychiatrie und Psychotherapie der Technischen Universität München	München
Germany	Universitäts - und Rehabilitationskliniken Ulm, Neurologie	Ulm
Italy	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
Netherlands	Alzheimer Research Center Amsterdam	Amsterdam
Netherlands	Jeroen Bosch Ziekenhuis, afdeling geriatrie	Den Bosch
Netherlands	Erasmus University Medical Center	Rotterdam
Poland	NZOZ Neuro-Kard Ilkowski i Partnerzy Spólka Partnerska	Poznan
Poland	Euromedis Sp. z o.o.	Szczecin
Romania	Psychomedical Consult	Bucharest
Singapore	National Neuroscience Institute Department of Neurology	Singapore
Spain	Fundació ACE. Institut Català de Neurociències Aplicades	Barcelona
Spain	Ceuta University Hospital; Neurology	Ceuta
Spain	Hospital Viamed Montecanal, Neurology Department	Zaragoza
United Kingdom	NHS Grampian, OAP Directorate	Aberdeen
United Kingdom	The Barberry Out-Patients Department	Birmingham
United Kingdom	2gether NHS foundation trust	Cheltenham
United Kingdom	Kingsway Hospital	Derby
United Kingdom	St Margaret's Hospital Mental Health Unit	Epping
United Kingdom	Cognition Health Ltd.	London
United Kingdom	Dementia Research Center at Queens Square	London
United Kingdom	Imperial College Healthcare NHS Trust - Charing Cross Hospital	London
United Kingdom	Nuffield Department of Clinical Neurosciences	Oxford
United Kingdom	Redwoods Centre	Shrewsbury
United Kingdom	Wessex Neurological Centre, Southampton General Hospital	Southampton
United States	Neurological Associates of Albany, P. C.	Albany	New York
United States	Department of Neurology, Emory University	Atlanta	Georgia
United States	Johns Hopkins University	Baltimore	Maryland
United States	The Memory Clinic	Bennington	Vermont
United States	Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital	Boston	Massachusetts
United States	Integrative Clinical Trials LLC	Brooklyn	New York
United States	Meridien Research	Brooksville	Florida
United States	UNC Department of Neurology, Physicians Office Building	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University Hospitals Case Medical Center, Neurology Clinical Trials Unit	Cleveland	Ohio
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Neurosciences Institute Clinical Research	Elk Grove Village	Illinois
United States	Indiana University Department of Neurology	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania
United States	David Geffen School of Medicine at UCLA, UCLA Neurological Services	Los Angeles	California
United States	The Shankle Clinic	Newport Beach	California
United States	Rivers Wellness and Research Institute	Oklahoma City	Oklahoma
United States	Compass Research, LLC	Orlando	Florida
United States	Hospital of the University of Pennsylvania, Department of Neurology	Philadelphia	Pennsylvania
United States	Mayo Clinic, Department of Neurology	Rochester	Minnesota
United States	PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic	Salt Lake City	Utah
United States	Memory and Aging Centre	San Francisco	California
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
TauRx Therapeutics Ltd

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Croatia,  Germany,  Italy,  Netherlands,  Poland,  Romania,  Singapore,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Early effect on modified ADCS-CGIC (change from Baseline)		8 weeks
Other	Change from Baseline on the rate of atrophy in frontal and temporal lobes as well as ventricular volume (assessed by brain MRI)		52 weeks
Other	Change from Baseline on Mini-Mental Status Examination (MMSE)		52 weeks
Other	Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III)		52 weeks
Other	Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD		52 weeks
Primary	Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R)		52 weeks
Primary	Change from Baseline on Functional Activities Questionnaire (FAQ)		52 weeks
Primary	Change from Baseline on whole brain volume (assessed by brain MRI)		52 weeks
Secondary	Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III)		52 weeks
Secondary	Change from Baseline on Frontotemporal Dementia Rating Scale (FRS)		52 weeks
Secondary	Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC)		52 weeks
Secondary	Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes	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	52 weeks