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

Phase 3

Completed

• Conditions: Behavioral Variant Frontotemporal Dementia (bvFTD)
• Interventions: Drug: TRx0237; 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

Study Timeline

• Study First Submitted: 2012-06-20
• Study First Submitted QC: 2012-06-20
• Study First Posted: 2012-06-22
• Study Start: 2013-05
• Primary Completion: 2016-02
• Study Completion: 2016-02
• Status Verified: 2018-03
• Disposition First Submitted: 2018-03-12
• Disposition First Submitted QC: 2018-03-12
• Last Update Submitted: 2018-03-12
• Disposition First Posted: 2018-03-14
• Last Update Posted: 2018-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 220

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

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
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
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

Trial Locations

Locations (67)

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

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