Clinical trial NCT03446001: Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Lead sponsor: TauRx Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2018-02-26
Enrollment: 598
Sex: ALL
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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