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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by TauRx Therapeutics Ltd
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier:
NCT01626378
First received: June 20, 2012
Last updated: August 4, 2014
Last verified: August 2014

June 20, 2012
August 4, 2014
August 2013
December 2015   (final data collection date for primary outcome measure)
  • Change from Baseline on Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (modified ADCS-CGIC) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Addenbrooke's Cognitive Examination - Revised (ACE-R) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Modified Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Addenbrooke's Cognitive Examination - Revised (ACE-R) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01626378 on ClinicalTrials.gov Archive Site
  • Change from Baseline on Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Frontotemporal Dementia Rating Scale (FRS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Functional Activities Questionnaire (FAQ) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
    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 in Unified Parkinson's Disease Rating Scale (UPDRS Parts II and III) [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  • Change from Baseline in Frontotemporal Dementia Rating Scale (FRS) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline in Functional Activities Questionnaire (FAQ) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Early effect on modified ADCS-CGIC (change from Baseline) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on whole brain volume (assessed by brain MRI) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Mini-Mental Status Examination (MMSE) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Change from Baseline on Addenbrooke's Cognitive Examination-III (ACE-III) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Determine the effect of TRx0237 in subjects with known genetic mutations associated with bvFTD [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
Not Provided
 
Safety and Efficacy Study Evaluating TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)
A Double-Blind, Placebo-Controlled, Randomized, Parallel Group, 12-Month Safety and Efficacy Trial of TRx0237 in Subjects With Behavioral Variant Frontotemporal Dementia (bvFTD)

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).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Behavioral Variant Frontotemporal Dementia (bvFTD)
  • Drug: TRx0237
    TRx0237 100 mg tablet will be administered twice daily.
  • 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.
  • Experimental: TRx0237 200 mg/day group
    Intervention: Drug: TRx0237
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
180
January 2016
December 2015   (final data collection date for primary outcome measure)

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 focal or vascular 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; magnetic resonance compatible prosthetics, clips, stents, or any other device proven to be compatible will be allowed
  • 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 (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
Both
up to 79 Years
No
United Kingdom,   United States,   Netherlands,   Australia,   Argentina,   Spain,   Germany,   Finland,   Poland,   Italy,   Canada,   Singapore,   Romania,   Croatia
 
NCT01626378
TRx-237-007
Yes
TauRx Therapeutics Ltd
TauRx Therapeutics Ltd
Not Provided
Not Provided
TauRx Therapeutics Ltd
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP