Clinical trial NCT01689246: Safety and Efficacy Study Evaluating TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease
Official title: Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 15-Month Trial of TRx0237 in Subjects With Mild to Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer's Disease
Keywords: Alzheimer's Disease
Alzheimer Disease
TRx0237
AD
Neurodegenerative Diseases
Dementia
Brain Diseases
Lead sponsor: TauRx Therapeutics Ltd
Sponsor class: INDUSTRY
First posted: 2012-09-21
Enrollment: 891
Sex: ALL
Maximum age (years): 89
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 in the treatment of subjects with mild to moderate Alzheimer's Disease.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of all cause dementia and probable Alzheimer's disease
* Clinical Dementia Rating (CDR) total score of 1 (mild) to 2 (moderate) and MMSE score of 14-26 (inclusive)
* Age \< 90 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 at the time of Screening, 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 Alzheimer's disease
* Significant focal or vascular intracranial pathology seen on brain MRI scan
* Clinical evidence or history of stroke, transient ischemic attack, significant head injury or other unexplained or recurrent loss of consciousness ≥15 minutes
* Epilepsy
* Major depressive disorder, schizophrenia, or other psychotic disorders, bipolar disorder, or 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 Alzheimer's disease
* 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 3 months before Baseline with any of the following medications:

  * Tacrine
  * Clozapine, olanzapine (and there is no intent to initiate therapy during the course of the study)
  * Carbamazepine, primidone
  * Drugs with 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, therapeutic device, or medical food in which the last dose/administration was received within 28 days prior to Baseline

Primary outcomes:
measure: Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23)
timeFrame: 65 weeks
measure: Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)
timeFrame: 65 weeks
measure: Number of study participants who tolerate oral doses of TRx0237 as determined by safety parameter changes
timeFrame: 65 weeks
Secondary outcomes:
measure: Change from Baseline on Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC)
timeFrame: 65 weeks
measure: Change from Baseline on Mini-Mental Status Examination (MMSE)
timeFrame: 65 weeks
measure: Change in expected decline of whole brain volume as measured by brain MRI
timeFrame: 39 weeks and 65 weeks
Other outcomes:
measure: Reduction in glucose uptake decline in the temporal lobe on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging
timeFrame: 39 weeks and 65 weeks
measure: Change in expected increase in ventricular volume and decline in hippocampal volume as evaluated by MRI
timeFrame: 39 weeks and 65 weeks
measure: Change in resource utilization using the Resource Utilization in Dementia (RUD) Lite
timeFrame: 65 weeks
measure: Change from Baseline on cerebrospinal fluid biomarkers of Alzheimer's Disease in subjects who separately consent to lumbar puncture
timeFrame: 65 weeks
measure: Compare the influence of Apolipoprotein E genotype on the primary and selected secondary outcomes in subjects by or for whom legally acceptable consent is separately provided
timeFrame: 65 weeks
Locations:
city: Phoenix
country: United States
facility: Xenoscience, Inc/ 21st Century Neurology
state: Arizona
city: Laguna Hills
country: United States
facility: Feldman, Robert MD
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Newport Beach
country: United States
facility: Shankle Clinic and Hoag Memorial Hospital Presbyterian
state: California
city: San Diego
country: United States
facility: Pacific Research Network
state: California
city: San Francisco
country: United States
facility: San Francisco Clinical Research Center
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Atlantis
country: United States
facility: JEM Research
state: Florida
city: Delray Beach
country: United States
facility: Brain Matters Research
state: Florida
city: Jacksonville
country: United States
facility: CNS Healthcare, Inc
state: Florida
city: Leesburg
country: United States
facility: Compass Research, LLC-North Clinic
state: Florida
city: Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Decatur
country: United States
facility: iResearch Atlanta
state: Georgia
city: Elk Grove
country: United States
facility: Alexian Brothers Neurosciences Institute
state: Illinois
city: Methuen
country: United States
facility: ActivMed Practices & Research
state: Massachusetts
city: Olive Branch
country: United States
facility: Olive Branch Family Medical
state: Mississippi
city: Eatontown
country: United States
facility: Memory Enhancement Centers of America, Inc
state: New Jersey
city: Marlton
country: United States
facility: CRI Worldwide
state: New Jersey
city: Springfield
country: United States
facility: The Cognitive Research Center of New Jersey
state: New Jersey
city: Toms River
country: United States
facility: Advanced Memory Research Institute of NJ PC
state: New Jersey
city: Albany
country: United States
facility: Neurological Associates of Albany, P. C.
state: New York
city: Brooklyn
country: United States
facility: SPRI
state: New York
city: Canton
country: United States
facility: Neurobehavioral Clinical Research
state: Ohio
city: Jenkintown
country: United States
facility: The Clinical Trial Center, LLC
state: Pennsylvania
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Hornsby
country: Australia
facility: Division of Rehabilitation and Aged Care
state: New South Wales
city: Kogarah
country: Australia
facility: Southern Neurology Pty Limited
state: New South Wales
city: Randwick
country: Australia
facility: Academic Department for Old Age Psychiatry, Prince of Wales Hospital
state: New South Wales
city: Herston
country: Australia
facility: Discipline of Psychiatry, University of Qld
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital Memory Trials Centre
state: South Australia
city: Woodville South
country: Australia
facility: Memory Unit, Neurology, The Queen Elizabeth Hospital
state: South Australia
city: Heidelberg West
country: Australia
facility: Medical and Cognitive Research Unit, Austin Health Heidelberg Repatriation Hospital
state: Victoria
city: Nedlands
country: Australia
facility: McCusker Alzheimer's Research Foundation Inc
state: Western Australia
city: Perth
country: Australia
facility: Neurodegenerative Disorders Research Pty Ltd
state: Western Australia
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska" Clinic of Neurology Diseases Department of Neurodegenerative and Immune and Infectious Diseases of Central Nervous System with Sector for Treatment of Neuroinfections
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska" Clinic of Psychiatry First Department of Psychiatry
city: Kelowna
country: Canada
facility: Okanagan Clinical Trials
state: British Columbia
city: Kentville
country: Canada
facility: True North Clinical Research Kentville Inc
state: Nova Scotia
city: North York
country: Canada
facility: Toronto Memory Program
state: Ontario
city: Zagreb
country: Croatia
facility: University Hospital Centre Zagreb
city: Zagreb
country: Croatia
facility: University Psychiatric Hospital Vrapce
city: Achim
country: Germany
facility: Neurozentrum Achim Dr. med. Andreas Mahler
city: Berlin
country: Germany
facility: Charité, University Medicine Berlin, CBF, Neurology
city: Berlin
country: Germany
facility: Memory Clinic, ECRC
city: Milano
country: Italy
facility: Neurologia Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Istituto Neurologico Carlo Besta
city: Pavia
country: Italy
facility: IRCCS Istituto neurologico Casimiro Mondino
city: Perugia
country: Italy
facility: Clinica Neurologica, Università di Perugia-Ospedale S. Maria della Misericordia
city: Roma
country: Italy
facility: Universita' Cattolica del Sacro Cuore
city: Roma
country: Italy
facility: Azienda Ospedaliera Universitaria Sant'Andrea di Roma- Unita' di Neurologia
city: Torino
country: Italy
facility: Dipartimento di Neuroscienze Universita' di Torino
city: Udine
country: Italy
facility: Azienda Ospedaliera S.maria Della Misericordia
city: Varese
country: Italy
facility: U.O. Di Neurologia Ospedale di Circolo e Fondazione Macchi
city: Busan
country: Korea, Republic of
facility: Dong-A Medical Center
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Inje University Sanggye Paik Hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Boramae Medical Center
city: Ipoh
country: Malaysia
facility: University Kuala Lumpur Royal College of Medicine
city: Johor Bahru
country: Malaysia
facility: Hospital Sultan Ismail
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Taiping
country: Malaysia
facility: Taiping Hospital
city: Białystok
country: Poland
facility: Podlaskie Centrum Psychogeriatrii
city: Bydgoszcz
country: Poland
facility: Pallmed sp zoo prowadząca NZOZ Dom Sue Ryder; Centrum Psychoneurologii Wieku Podeszłego
city: Katowice
country: Poland
facility: NZOZ Wielospecjalistyczna Poradnia Lekarska SYNAPSIS
city: Mosina
country: Poland
facility: Gabinet Neurologiczny, Indywidualna Specjalistyczna Praktyka Lekarska
city: Poznań
country: Poland
facility: NZOZ Neuro-Kard Ilkowski i Partnerzy Spółka Partnerska Lekarzy
city: Szczecin
country: Poland
facility: Euromedis Sp. z o.o.
city: Warszawa
country: Poland
facility: Usługi Lekarskie Sp.c Palasik, Żabierek
city: Warszawa
country: Poland
facility: mMED
city: Warszawa
country: Poland
facility: MTZ Clinical Research Sp. z o.o.
city: Arad
country: Romania
facility: County Emergency Clinical Hospital Arad, Psychiatry Department
city: Brasov
country: Romania
facility: CMDTA "Neomed"
city: Bucharest
country: Romania
facility: University Emergency Central Military Hospital "Dr.Carol Davila", Psychiatry Department
city: Bucharest
country: Romania
facility: Psychomedical Consult
city: Oradea
country: Romania
facility: Clinical Municipal Hospital "Dr. Gavril Curteanu", Psychiatry Department
city: Sibiu
country: Romania
facility: Psychiatry Hospital "Dr. Gheorghe Preda", Center of Mental Health
city: Sibiu
country: Romania
facility: Psychiatry Hospital "Dr. Gheorghe Preda", Department of Psychiatry III
city: Sibiu
country: Romania
facility: Emergency Clinical County Hospital Sibiu, Neurology Department
city: Ekaterinburg
country: Russian Federation
facility: State Budgetary Healthcare Institution of Sverdlovsk region "Sverdlovsk Regional Clinical Psychiatric Hospital"
city: Moscow
country: Russian Federation
facility: Non-governmental Healthcare Institution "Central Clinical Hospital #6 of the JSC "Russian Railways"
city: Moscow
country: Russian Federation
facility: Mental Health Research Center of the Russian Academy of Medical Sciences, Gerontopsychiatry department
city: Moscow
country: Russian Federation
facility: Mental Health Research Center of the Russian Academy of Medical Sciences
city: Novosibirsk
country: Russian Federation
facility: CityClinical Hospital #34, City Scientific Practical Neurological Center
city: Saint Petersburg
country: Russian Federation
facility: City Geriatric Medical and Social Center
city: Saint Petersburg
country: Russian Federation
facility: Saint Nicholas Psychiatric Hospital
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg Psychoneurological Research Institute n. a. V.M. Bekhterev
city: Singapore
country: Singapore
facility: National University Hospital (NUH)
city: Singapore
country: Singapore
facility: National Neuroscience Institute (NNI)
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital (TTSH)
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Ceuta
country: Spain
facility: Hospital Universitario de Ceuta
city: Córdoba
country: Spain
facility: Hospital Reina Sofía
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Zaragoza
country: Spain
facility: Hospital Viamed Montecanal
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital, Kaohsiung
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taipei
country: Taiwan
facility: En Chu Kong Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: National Yang-Ming University School of Medicine
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital, Linkou
city: Aberdeen
country: United Kingdom
facility: NHS Grampian, Department of Old Age Psychiatry Royal Cornhill Hospital
city: Bath
country: United Kingdom
facility: RICE - The Research Institute for the Care of Older People
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust (BHSCT)
city: Birmingham
country: United Kingdom
facility: The Barberry Centre
city: Blackpool
country: United Kingdom
facility: MAC Clinical Research Ltd
city: Bradford
country: United Kingdom
facility: MAC Clinical Research Ltd
city: Cannock
country: United Kingdom
facility: MAC Clinical Research Ltd
city: Leeds
country: United Kingdom
facility: MAC Clinical Research Ltd
city: London
country: United Kingdom
facility: Re: Cognition Health Ltd.
city: London
country: United Kingdom
facility: Charing Cross Hospital
city: London
country: United Kingdom
facility: Dementia Research Centre
city: Manchester
country: United Kingdom
facility: MAC Clinical Research Ltd
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
Study officials:
References:
citation: Gauthier S, Feldman HH, Schneider LS, Wilcock GK, Frisoni GB, Hardlund JH, Moebius HJ, Bentham P, Kook KA, Wischik DJ, Schelter BO, Davis CS, Staff RT, Bracoud L, Shamsi K, Storey JM, Harrington CR, Wischik CM. Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet. 2016 Dec 10;388(10062):2873-2884. doi: 10.1016/S0140-6736(16)31275-2. Epub 2016 Nov 16.