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

NCT ID: NCT01626378

Last Updated: 2018-03-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 220 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2016-02-29

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).

Conditions

Behavioral Variant Frontotemporal Dementia (bvFTD)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

TRx0237 200 mg/day group

Group Type: EXPERIMENTAL

TRx0237

Intervention Type: DRUG

TRx0237 100 mg tablet will be administered twice daily.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

TRx0237

TRx0237 100 mg tablet will be administered twice daily.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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

• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

TauRx Therapeutics Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

David Geffen School of Medicine at UCLA, UCLA Neurological Services

Los Angeles, California, United States

The Shankle Clinic

Newport Beach, California, United States

Memory and Aging Centre

San Francisco, California, United States

Meridien Research

Brooksville, Florida, United States

Mayo Clinic

Jacksonville, Florida, United States

Compass Research, LLC

Orlando, Florida, United States

University of South Florida

Tampa, Florida, United States

Department of Neurology, Emory University

Atlanta, Georgia, United States

Alexian Brothers Neurosciences Institute Clinical Research

Elk Grove Village, Illinois, United States

Indiana University Department of Neurology

Indianapolis, Indiana, United States

Johns Hopkins University

Baltimore, Maryland, United States

Neurological Clinical Research Institute (NCRI) Massachusetts General Hospital

Boston, Massachusetts, United States

Mayo Clinic, Department of Neurology

Rochester, Minnesota, United States

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States

Neurological Associates of Albany, P. C.

Albany, New York, United States

Integrative Clinical Trials LLC

Brooklyn, New York, United States

UNC Department of Neurology, Physicians Office Building

Chapel Hill, North Carolina, United States

University Hospitals Case Medical Center, Neurology Clinical Trials Unit

Cleveland, Ohio, United States

Rivers Wellness and Research Institute

Oklahoma City, Oklahoma, United States

The Clinical Trial Center, LLC

Jenkintown, Pennsylvania, United States

Hospital of the University of Pennsylvania, Department of Neurology

Philadelphia, Pennsylvania, United States

PRA Health Sciences, Phase 2/3 Outpatient and CNS Clinic

Salt Lake City, Utah, United States

The Memory Clinic

Bennington, Vermont, United States

University of Virginia

Charlottesville, Virginia, United States

Neuroscience Research Australia

Randwick, New South Wales, Australia

Box Hill Hospital

Box Hill, Victoria, Australia

Neurodegenerative Disorders Research Pty Ltd

West Perth, Western Australia, Australia

Heritage Medical Research Clinic-University of Calgary

Calgary, Alberta, Canada

University of British Columbia Hospital, Clinic for Alzheimer Disease and Related Disorders

Vancouver, British Columbia, Canada

Vancouver Island Health Authority

Victoria, British Columbia, 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

McGill Centre for Studies in Aging, Alzheimer Disease Research Unit

Verdun, Quebec, Canada

University Hospital Centre Zagreb

Zagreb, , Croatia

University Psychiatric Hospital Vrapče

Zagreb, , Croatia

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, , Germany

Unità di Neuroimmagine e Epidemiologia Alzheimer

Brescia, , Italy

Fondazione Universita' Gabriele D'Annunzio di Chieti

Chieti Scalo, , Italy

Fondazione IRCCS Istituto Neurologico "Carlo Besta"

Milan, , Italy

Neurology I, Department of Neuroscience, University of Torino

Torino, , Italy

Jeroen Bosch Ziekenhuis, afdeling geriatrie

's-Hertogenbosch, , Netherlands

Alzheimer Research Center Amsterdam

Amsterdam, , Netherlands

Erasmus University Medical Center

Rotterdam, , Netherlands

NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska

Poznan, , Poland

Euromedis Sp. z o.o.

Szczecin, , Poland

Psychomedical Consult

Bucharest, , Romania

National Neuroscience Institute Department of Neurology

Singapore, , Singapore

Fundació ACE. Institut Català de Neurociències Aplicades

Barcelona, , Spain

Ceuta University Hospital; Neurology

Ceuta, , Spain

Hospital Viamed Montecanal, Neurology Department

Zaragoza, , Spain

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

Imperial College Healthcare NHS Trust - Charing Cross Hospital

London, , United Kingdom

Dementia Research Center at Queens Square

London, , United Kingdom

Nuffield Department of Clinical Neurosciences

Oxford, , United Kingdom

Redwoods Centre

Shrewsbury, , United Kingdom

Wessex Neurological Centre, Southampton General Hospital

Southampton, , United Kingdom

Countries

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

References

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.

Reference Type: DERIVED

PMID: 24819148 (View on PubMed)

Other Identifiers

TRx-237-007

Identifier Type: -

Identifier Source: org_study_id