Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment
- Conditions
- Alzheimer Disease
- Interventions
- Drug: PlaceboDrug: TRx0237 16 mg/dayDrug: TRx0237 8 mg/day
- Registration Number
- NCT03446001
- Lead Sponsor
- TauRx Therapeutics Ltd
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 598
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - TRx0237 16 mg/day TRx0237 16 mg/day - TRx0237 8 mg/day TRx0237 8 mg/day -
- Primary Outcome Measures
Name Time Method Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) Baseline and 52 weeks 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).
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) Baseline and 52 weeks 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).
Number of study participants with serious and non-serious adverse events Up to 52 weeks 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.
- Secondary Outcome Measures
Name Time Method Change in annualized rate of whole brain atrophy Baseline and 52 weeks This secondary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group.
Change in Standardized Uptake Value Ratio (SUVR) based on temporal lobe 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) Baseline and 52 weeks 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.
Change in annualized rate of temporal and parietal lobe atrophy Baseline and 52 weeks This secondary outcome measure will be assessed in each of the TRx0237 dose groups compared to the placebo group.
Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) Baseline and 52 weeks 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).
Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) Baseline and 52 weeks 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).
Change from Open-Label Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) 52 weeks and 104 weeks 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).
Number of study participants with serious and non-serious adverse events Up to 104 weeks 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.
Trial Locations
- Locations (98)
Visionary Investigators Network
🇺🇸Miami, Florida, United States
Finlay Medical Research
🇺🇸Miami, Florida, United States
Health Care Family Rehab and Research
🇺🇸Miami, Florida, United States
Vitae Research Center, LLC
🇺🇸Miami, Florida, United States
Future Care Solution, LLC
🇺🇸Miami, Florida, United States
Florida International Research Center
🇺🇸Miami, Florida, United States
Miami Dade Medical Research Institute, LLC
🇺🇸Miami, Florida, United States
Josephson Wallack Munshower Neurology P.C.
🇺🇸Indianapolis, Indiana, United States
ATP Clinical Research, Inc.
🇺🇸Costa Mesa, California, United States
Fullerton Neurology and Headache Center
🇺🇸Fullerton, California, United States
Imaging Endpoints Research
🇺🇸Scottsdale, Arizona, United States
HB Clinical Trials Inc.
🇺🇸Fountain Valley, California, United States
Hospitales de Madrid
🇪🇸Madrid, Spain
Hospital Virgen de la Macarena
🇪🇸Sevilla, Spain
Alpha Recherche Clinique
🇨🇦Québec, Canada
Hospital Universitario Mutua Terrassa
🇪🇸Terrassa, Spain
Atria Clinical Research
🇺🇸Little Rock, Arkansas, United States
Sharp Mesa Vista Hospital
🇺🇸San Diego, California, United States
Ospedale San Giovanni Calibita Fatebenefratelli
🇮🇹Roma, Italy
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital General de Catalunya
🇪🇸Barcelona, Spain
Alzheimer's Research and Treatment Center
🇺🇸Wellington, Florida, United States
Centrum Medyczne NEUROMED
🇵🇱Bydgoszcz, Poland
Re:Cognition Health - Central London
🇬🇧London, United Kingdom
Hospital Universitario QuironSalud Madrid
🇪🇸Madrid, Spain
Clinica Neurologica Santa Maria della Misericordia
🇮🇹Udine, Italy
The Roskamp Institute, Inc.
🇺🇸Sarasota, Florida, United States
Azienda Ospedaliera Sant'Andrea
🇮🇹Roma, Italy
Podlaskie Centrum Psychogeriatrii
🇵🇱Bialystok, Poland
Hôpital Neurologique Pierre Wertheimer
🇫🇷Bron, France
Centro de salud de San Juan, Unidad de Investigación Neurociencias
🇪🇸Salamanca, Spain
IRCCS Fondazione Santa Lucia
🇮🇹Rome, Italy
Hôpital Laënnec - CHU de Nantes
🇫🇷Nantes, France
University of Perugia, Ospedale S.M. della Misericordia
🇮🇹Perugia, Italy
Okanagan Clinical Trials, Ltd.
🇨🇦Kelowna, British Columbia, Canada
Euromedis Sp. z o.o.
🇵🇱Szczecin, Poland
NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
🇵🇱Katowice, Poland
Indywidualna Praktyka Lekarska
🇵🇱Lublin, Poland
Xenoscience
🇺🇸Phoenix, Arizona, United States
Arizona Research Center
🇺🇸Phoenix, Arizona, United States
IPS Research Company
🇺🇸Oklahoma City, Oklahoma, United States
Neural Net Research
🇺🇸Portland, Oregon, United States
Hospital Universitario Doctor Peset
🇪🇸Valencia, Spain
CHU Bordeaux - Pellegrin
🇫🇷Bordeaux, France
California Neuroscience Medical Group
🇺🇸Sherman Oaks, California, United States
Excell Research, Inc.
🇺🇸Oceanside, California, United States
Syrentis Clinical Research
🇺🇸Santa Ana, California, United States
Senior Clinical Trials, Inc.
🇺🇸Laguna Hills, California, United States
Guidechauliac Hospital
🇫🇷Montpellier, France
MD Clinical
🇺🇸Hallandale Beach, Florida, United States
Indago Research & Health Center, Inc.
🇺🇸Hialeah, Florida, United States
Merrit Island Medical Research
🇺🇸Merritt Island, Florida, United States
Optimus Clinical Research
🇺🇸Miami, Florida, United States
CCM Clinical Research Group
🇺🇸Miami, Florida, United States
Advance Medical Research Center
🇺🇸Miami, Florida, United States
L&C Professional Medical Research Institute
🇺🇸Miami, Florida, United States
Biomed Research Institute, Inc
🇺🇸Miami, Florida, United States
Allied Biomedical Research Institute
🇺🇸Miami, Florida, United States
Sensible Healthcare
🇺🇸Ocoee, Florida, United States
IMIC Inc
🇺🇸Palmetto Bay, Florida, United States
Emerald Coast Center for Neurological Disorders
🇺🇸Pensacola, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
NeuroStudies.net, LLC
🇺🇸Decatur, Georgia, United States
Georgia Neurology and Sleep Medicine Associates
🇺🇸Suwanee, Georgia, United States
Advanced Memory Research of NJ PC
🇺🇸Toms River, New Jersey, United States
UBMD Neurology
🇺🇸Buffalo, New York, United States
Neuroscience Research Center, LLC
🇺🇸Canton, Ohio, United States
Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
Albany Medical College
🇺🇸Albany, New York, United States
Richmond Behavioral Associates
🇺🇸Staten Island, New York, United States
Valley Medical Research
🇺🇸Centerville, Ohio, United States
Neuro-Behavioral Clinical Research, Inc.
🇺🇸North Canton, Ohio, United States
The Lindner Research Center
🇺🇸Cincinnati, Ohio, United States
Neurology Diagnostics Inc.
🇺🇸Dayton, Ohio, United States
Coastal Neurology
🇺🇸Port Royal, South Carolina, United States
Kingfisher Cooperative, LLC
🇺🇸Spokane, Washington, United States
Universal Research Group, LLC
🇺🇸Tacoma, Washington, United States
Re:Cognition Health
🇬🇧Plymouth, United Kingdom
Cliniques Universitaires Saint-Luc
🇧🇪Bruxelles, Belgium
Clinique Mémoire de l'Outaouais
🇨🇦Gatineau, Quebec, Canada
Memory Clinic (Ottawa)
🇨🇦Ottawa, Ontario, Canada
Timone Adults Hospital
🇫🇷Marseille, France
CHU de Limoges
🇫🇷Limoges, France
CRC Gerontopole Cite de la Sante, Hôpital La Grave
🇫🇷Toulouse, France
Azienda Ospedaliera San Gerardo - Clinica Neurologica
🇮🇹Monza, Italy
CHU de Rennes
🇫🇷Rennes, France
IRCCS Centro S. Giovanni di Dio Fatebenefratelli
🇮🇹Brescia, Italy
Foundation Institute G.Giglio
🇮🇹Cefalù, Italy
Hopital des Charpennes
🇫🇷Villeurbanne, France
Istituto Neurologico Casimiro Mondino, IRCCS
🇮🇹Pavia, Italy
Centrum Medyczne NeuroProtect
🇵🇱Warszawa, Poland
NZOZ Neuro-Kard
🇵🇱Poznań, Poland
Glasgow Memory Clinic Ltd
🇬🇧Glasgow, United Kingdom
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Tulsa Clinical Research LLC
🇺🇸Tulsa, Oklahoma, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
CBRI - Roper Hospital
🇺🇸Charleston, South Carolina, United States
Bioclinica Research
🇺🇸Orlando, Florida, United States