Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment

Randomized, Double-Blind, Placebo-Controlled, Three-Arm, 12-Month, Safety and Efficacy Study of TRx0237 Monotherapy in Subjects With Alzheimer's Disease Followed by a 12-Month Open-Label Treatment

The purpose of this study is to determine the safety and efficacy of TRx0237 16 mg/day and 8 mg/day in the treatment of subjects with Alzheimer's Disease compared to placebo. In addition, an open-label, delayed-start phase is included to demonstrate a disease-modifying effect of TRx0237.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: TRx0237 16 mg/day; Drug: Placebo; Drug: TRx0237 8 mg/day

• Study Type: Interventional
• Enrollment (Actual): 598
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques universitaires Saint-Luc
• Canada
  • Québec, Canada, G3K 2P8
    • Alpha Recherche Clinique
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials, Ltd.
  • Ontario
    • Ottawa, Ontario, Canada, K1Z 1G3
      • Memory Clinic (Ottawa)
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique Mémoire de l'Outaouais
• France
  • Bordeaux, France, 33076
    • CHU Bordeaux - Pellegrin
  • Bron, France, 69677
    • Hôpital Neurologique Pierre Wertheimer
  • Limoges, France, 87042
    • chu de Limoges
  • Marseille, France, 13385
    • Timone Adults Hospital
  • Montpellier, France, 34295
    • Guidechauliac Hospital
  • Nantes, France, 44093
    • Hopital Laennec - CHU de Nantes
  • Rennes, France, 35009
    • CHU de Rennes
  • Toulouse, France, 31059
    • CRC Gerontopole Cite de la Sante, Hôpital La Grave
  • Villeurbanne, France, 69100
    • Hôpital des charpennes
• Italy
  • Brescia, Italy, 25125
    • IRCCS Centro S. Giovanni di Dio Fatebenefratelli
  • Cefalù, Italy, 90015
    • Foundation Institute G.Giglio
  • Monza, Italy, 20900
    • Azienda Ospedaliera San Gerardo - Clinica Neurologica
  • Pavia, Italy, 27100
    • Istituto Neurologico Casimiro Mondino, IRCCS
  • Perugia, Italy, 06156
    • University of Perugia, Ospedale S.M. della Misericordia
  • Roma, Italy, 00189
    • Azienda Ospedaliera Sant'Andrea
  • Roma, Italy, 00186
    • Ospedale San Giovanni Calibita Fatebenefratelli
  • Rome, Italy, 00179
    • IRCCS Fondazione Santa Lucia
  • Udine, Italy, 33100
    • Clinica Neurologica Santa Maria della Misericordia
• Poland
  • Bialystok, Poland, 15-756
    • Podlaskie Centrum Psychogeriatrii
  • Bydgoszcz, Poland, 85-163
    • Centrum Medyczne NEUROMED
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
  • Lublin, Poland, 20-582
    • Indywidualna Praktyka Lekarska
  • Poznań, Poland, 61-853
    • NZOZ Neuro-kard
  • Szczecin, Poland, 70-111
    • EUROMEDIS Sp. z o.o.
  • Warszawa, Poland, 01-684
    • Centrum Medyczne NeuroProtect
• Spain
  • Barcelona, Spain, 08195
    • Hospital General de Catalunya
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28223
    • Hospital Universitario Quironsalud Madrid
  • Madrid, Spain, 28015
    • Hospitales de Madrid
  • Salamanca, Spain, 37005
    • Centro de salud de San Juan, Unidad de Investigación Neurociencias
  • Sevilla, Spain, 41009
    • Hospital Virgen de la Macarena
  • Terrassa, Spain, 08222
    • Hospital Universitario Mutua Terrassa
  • Valencia, Spain, 46017
    • Hospital Universitario Doctor Peset
• United Kingdom
  • Birmingham, United Kingdom, B16 8LT
    • Re:Cognition Health
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic Ltd
  • Guildford, United Kingdom, GU2 7YD
    • Re:Cognition Health
  • London, United Kingdom, W1G 9JF
    • Re:Cognition Health - Central London
  • Plymouth, United Kingdom, PL6 8BT
    • Re:Cognition Health
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85053
      • Arizona Research Center
    • Phoenix, Arizona, United States, 85004
      • Xenoscience
    • Scottsdale, Arizona, United States, 85258
      • Imaging Endpoints Research
  • Arkansas
    • Little Rock, Arkansas, United States, 72209
      • Atria Clinical Research
  • California
    • Costa Mesa, California, United States, 92626
      • ATP Clinical Research, Inc.
    • Fountain Valley, California, United States, 92708
      • HB Clinical Trials Inc.
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • Laguna Hills, California, United States, 92653
      • Senior Clinical Trials, Inc.
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital Presbyterian
    • Oceanside, California, United States, 92056
      • Excell Research, Inc.
    • San Diego, California, United States, 92123
      • Sharp Mesa Vista Hospital
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
    • Sherman Oaks, California, United States, 91403
      • California Neuroscience Medical Group
  • Florida
    • Aventura, Florida, United States, 33180
      • Visionary Investigators Network
    • Greenacres City, Florida, United States, 33467
      • Finlay Medical Research
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc.
    • Merritt Island, Florida, United States, 32952
      • Merrit Island Medical Research
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Miami, Florida, United States, 33133
      • CCM Clinical Research Group
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute
    • Miami, Florida, United States, 33173
      • Florida International Research Center
    • Miami, Florida, United States, 33165
      • Future Care Solution, LLC
    • Miami, Florida, United States, 33176
      • Miami Dade Medical Research Institute, LLC
    • Miami, Florida, United States, 33135
      • Advance Medical Research Center
    • Miami, Florida, United States, 33135
      • Vitae Research Center, LLC
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute
    • Miami, Florida, United States, 33176
      • Visionary Investigators Network
    • Miami, Florida, United States, 33126
      • BioMed Research Institute, INC
    • Miami, Florida, United States, 33015
      • Health Care Family Rehab and Research
    • Miami, Florida, United States, 33125
      • Optimus Clinical Research
    • Ocoee, Florida, United States, 34761
      • Sensible Healthcare
    • Orlando, Florida, United States, 32806
      • Bioclinica Research
    • Palmetto Bay, Florida, United States, 33157
      • IMIC Inc
    • Pensacola, Florida, United States, 32504
      • Emerald Coast Center for Neurological Disorders
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • Sarasota, Florida, United States, 34243
      • The Roskamp Institute, Inc.
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Wellington, Florida, United States, 33414
      • Alzheimer's Research and Treatment Center
  • Georgia
    • Decatur, Georgia, United States, 30033
      • NeuroStudies.net, LLC
    • Suwanee, Georgia, United States, 30024
      • Georgia Neurology and Sleep Medicine Associates
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology P.C.
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research of NJ PC
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical College
    • Buffalo, New York, United States, 14203
      • UBMD Neurology
    • Staten Island, New York, United States, 10312
      • Richmond Behavioral Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer's Memory Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Neuroscience Research Center, LLC
    • Centerville, Ohio, United States, 45459
      • Valley Medical Research
    • Cincinnati, Ohio, United States, 45219
      • The Lindner Research Center
    • Dayton, Ohio, United States, 45459
      • Neurology Diagnostics Inc.
    • North Canton, Ohio, United States, 44321
      • Neuro-Behavioral Clinical Research, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73106
      • IPS Research Company
    • Tulsa, Oklahoma, United States, 74136
      • Tulsa Clinical Research LLC
  • Oregon
    • Portland, Oregon, United States, 97225
      • Neural Net Research
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • CBRI - Roper Hospital
    • Port Royal, South Carolina, United States, 29935
      • Coastal Neurology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Re:Cognition Health
  • Washington
    • Spokane, Washington, United States, 99202
      • Kingfisher Cooperative, LLC
    • Tacoma, Washington, United States, 98405
      • Universal Research Group, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 90 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Alzheimer's Disease (AD), encompassing probable AD and mild cognitive impairment due to AD (MCI-AD) based on the 2011 National Institute on Aging and Alzheimer's Association (NIA/AA) criteria
• Documented PET scan that is positive for amyloid
• Mini-Mental State Examination (MMSE) score of 16-27 (inclusive), subject to stratification requirements
• Global Clinical Dementia Rating (CDR) of 0.5 to 2 (if 0.5, including a score of >0 in one of the functional domains: Community Affairs, Home and Hobbies, or Personal Care)
• Age <90 years
• Females must be surgically sterile, have undergone bilateral tubal occlusion / ligation, be post-menopausal, or use adequate contraception
• Subject, and/or, in the case of reduced decision-making capacity, legally acceptable representative(s) consistent with local and national law is/are able to read, understand, and provide written informed consent in the designated language of the study site
• Has one or more identified adult study partner who either lives with the subject or has sufficient contact to provide assessment of changes in subject behavior and function over time and information on safety and tolerability; is willing to provide written informed consent for his/her own participation; is able to read, understand, and speak the designated language(s) at the study site; agrees to accompany the subject to each study visit; and is able to verify daily compliance with study drug
• Must not be taking an acetylcholinesterase inhibitor and/or memantine for at least 60 days at the time of the Baseline assessments
• Able to comply with the study procedures in the view of the Investigator

Exclusion Criteria:

• Significant central nervous system disorder other than probable AD or MCI-AD
• Significant intracranial focal or vascular pathology seen on brain MRI scan that would lead to a diagnosis other than probable AD or MCI-AD
• Clinical evidence or history of cerebrovascular accident; transient ischemic attack; significant head injury, for example, associated loss of consciousness, skull fracture or persisting cognitive impairment; other unexplained or recurrent loss of consciousness for ≥15 minutes
• Epilepsy (a single prior seizure >6 months prior to Screening is considered acceptable)
• Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria met for major depressive disorder; schizophrenia; other psychotic disorders, bipolar disorder; substance (including alcohol) related disorders
• Metal implants in the head, 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
• Any physical disability that would prevent completion of study procedures or assessments
• History of swallowing difficulties
• Pregnant or breastfeeding
• Glucose-6-phosphate dehydrogenase (G6PD) 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 significant by the Investigator
• Clinically significant cardiovascular disease or abnormal electrocardiogram assessments
• Pre-existing or current signs or symptoms of respiratory failure
• Concurrent acute or chronic clinically significant immunologic, hepatobiliary, or endocrine disease and/or other unstable or major disease other than probable AD or MCI-AD
• Diagnosis of cancer (excluding basal cell carcinoma, squamous cell carcinoma, or prostate carcinoma in situ [Stage 1]) within the past 2 years or a previous (>2 years) diagnosis of cancer that has required any form of intervention or treatment within the past 2 years
• Prior intolerance or hypersensitivity to methylthioninium (MT)-containing drug or methemoglobinemia induced by MT-containing drug, similar organic dyes, or any of the excipients
• Treatment currently or within 90 days before Baseline with Souvenaid®, clozapine, carbamazepine, primidone, valproate, or drugs for which there is a warning or precaution in the labeling about methemoglobinemia at approved doses
• Current or prior participation in any clinical trial of TRx0237; a clinical trial of a product for cognition prior to Baseline in which the last dose was received within 90 days prior to Baseline unless confirmed to have been randomized to placebo; or a clinical trial of any other investigational drug, biologic, device, or medical food in which the last dose was received within 28 days prior to Baseline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Oral placebo tablets (some of which contain a urinary discolorant) administered twice daily
Experimental: TRx0237 16 mg/day	Drug: TRx0237 16 mg/day; Oral TRx0237 4-mg tablets administered twice daily
Experimental: TRx0237 8 mg/day	Drug: TRx0237 8 mg/day; Oral TRx0237 4-mg tablet administered twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	This primary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group. The scores on this scale range from 0 to 70, with higher numbers indicating a worse outcome (greater impairment).	Baseline and 52 weeks
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	This primary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group. The scores on this scale range from 0 to 78, with higher numbers indicating a better outcome (lower impairment).	Baseline and 52 weeks
Number of study participants with serious and non-serious adverse events	This primary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group. All laboratory test or vital sign parameter abnormalities deemed clinically significant by the Investigator are to be reported as adverse events.	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in annualized rate of whole brain atrophy	This secondary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group.	Baseline and 52 weeks
Change in Standardized Uptake Value Ratio (SUVR) based on temporal lobe 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET)	This secondary outcome measure will be assessed in each of the TRx0237 dose groups compared to the placebo group, and restricted to subjects with Clinical Dementia Rating (CDR) 0.5 at Screening.	Baseline and 52 weeks
Change in annualized rate of temporal and parietal lobe atrophy	This secondary outcome measure will be assessed in each of the TRx0237 dose groups compared to the placebo group.	Baseline and 52 weeks
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	This secondary outcome measure will be assessed in the TRx0237 8 mg/day group compared to the placebo group. The scores on this scale range from 0 to 70, with higher numbers indicating a worse outcome (greater impairment).	Baseline and 52 weeks
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)	This secondary outcome measure will be assessed in the TRx0237 8 mg/day group compared to the placebo group. The scores on this scale range from 0 to 78, with higher numbers indicating a better outcome (lower impairment).	Baseline and 52 weeks
Change from Open-Label Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)	This secondary outcome measure will be assessed for the open-label period of the study comparing subjects originally randomized to placebo to subjects originally randomized to either dose of TRx0237. The scores on this scale range from 0 to 70, with higher numbers indicating a worse outcome (greater impairment).	52 weeks and 104 weeks
Number of study participants with serious and non-serious adverse events	This secondary outcome measure will be assessed in the TRx0237 8 mg/day group compared to the placebo group over 52 weeks and for all subjects receiving TRx0237 up to 104 weeks. All laboratory test or vital sign parameter abnormalities deemed clinically significant by the Investigator are to be reported as adverse events.	Up to 104 weeks

Collaborators and Investigators

• Sponsor: TauRx Therapeutics Ltd

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): April 4, 2023

Study Registration Dates

• First Submitted: February 8, 2018
• First Submitted That Met QC Criteria: February 20, 2018
• First Posted (Actual): February 26, 2018

Study Record Updates

• Last Update Posted (Actual): May 24, 2023
• Last Update Submitted That Met QC Criteria: May 22, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Methylene Blue
• Other Study ID Numbers: TRx-237-039

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No