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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03446001
Recruitment Status : Active, not recruiting
First Posted : February 26, 2018
Last Update Posted : September 23, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: TRx0237 16 mg/day Drug: Placebo Drug: TRx0237 8 mg/day Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 598 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: 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
Actual Study Start Date : January 10, 2018
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TRx0237 16 mg/day Drug: TRx0237 16 mg/day
Oral TRx0237 4-mg tablets administered twice daily

Placebo Comparator: Placebo Drug: Placebo
Oral placebo tablets (some of which contain a urinary discolorant) administered twice daily

Experimental: TRx0237 8 mg/day Drug: TRx0237 8 mg/day
Oral TRx0237 4-mg tablet administered twice daily




Primary Outcome Measures :
  1. Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 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).

  2. Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 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).

  3. Number of study participants with serious and non-serious adverse events [ Time Frame: 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 :
  1. Change in annualized rate of whole brain atrophy [ Time Frame: Baseline and 52 weeks ]
    This secondary outcome measure will be assessed in the TRx0237 16 mg/day group compared to the placebo group.

  2. Change in Standardized Uptake Value Ratio (SUVR) based on temporal lobe 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) [ Time Frame: 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.

  3. Change in annualized rate of temporal and parietal lobe atrophy [ Time Frame: Baseline and 52 weeks ]
    This secondary outcome measure will be assessed in each of the TRx0237 dose groups compared to the placebo group.

  4. Change from Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 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).

  5. Change from Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) [ Time Frame: 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).

  6. Change from Open-Label Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) [ Time Frame: 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).

  7. Number of study participants with serious and non-serious adverse events [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 90 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03446001


Locations
Hide Hide 103 study locations
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United States, Arizona
Xenoscience
Phoenix, Arizona, United States, 85004
Arizona Research Center
Phoenix, Arizona, United States, 85053
Imaging Endpoints Research
Scottsdale, Arizona, United States, 85258
United States, Arkansas
Atria Clinical Research
Little Rock, Arkansas, United States, 72209
United States, California
ATP Clinical Research, Inc.
Costa Mesa, California, United States, 92626
HB Clinical Trials Inc.
Fountain Valley, California, United States, 92708
Fullerton Neurology and Headache Center
Fullerton, California, United States, 92835
Senior Clinical Trials, Inc.
Laguna Hills, California, United States, 92653
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States, 92663
Excell Research, Inc.
Oceanside, California, United States, 92056
Sharp Mesa Vista Hospital
San Diego, California, United States, 92123
Syrentis Clinical Research
Santa Ana, California, United States, 92705
California Neuroscience Medical Group
Sherman Oaks, California, United States, 91403
United States, Florida
Visionary Investigators Network
Aventura, Florida, United States, 33180
Finlay Medical Research
Greenacres City, Florida, United States, 33467
MD Clinical
Hallandale Beach, Florida, United States, 33009
Indago Research & Health Center, Inc.
Hialeah, Florida, United States, 33012
Merrit Island Medical Research
Merritt Island, Florida, United States, 32952
Health Care Family Rehab and Research
Miami, Florida, United States, 33015
Optimus Clinical Research
Miami, Florida, United States, 33125
Biomed Research Institute, Inc
Miami, Florida, United States, 33126
Finlay Medical Research
Miami, Florida, United States, 33126
CCM Clinical Research Group
Miami, Florida, United States, 33133
Advance Medical Research Center
Miami, Florida, United States, 33135
Vitae Research Center, LLC
Miami, Florida, United States, 33135
L&C Professional Medical Research Institute
Miami, Florida, United States, 33144
Allied Biomedical Research Institute
Miami, Florida, United States, 33155
Future Care Solution, LLC
Miami, Florida, United States, 33165
Florida International Research Center
Miami, Florida, United States, 33173
Miami Dade Medical Research Institute, LLC
Miami, Florida, United States, 33176
Visionary Investigators Network
Miami, Florida, United States, 33176
Sensible Healthcare
Ocoee, Florida, United States, 34761
Bioclinica Research
Orlando, Florida, United States, 32806
IMIC Inc
Palmetto Bay, Florida, United States, 33157
Emerald Coast Center for Neurological Disorders
Pensacola, Florida, United States, 32504
Progressive Medical Research
Port Orange, Florida, United States, 32127
The Roskamp Institute, Inc.
Sarasota, Florida, United States, 34243
Stedman Clinical Trials
Tampa, Florida, United States, 33613
Alzheimer's Research and Treatment Center
Wellington, Florida, United States, 33414
United States, Georgia
NeuroStudies.net, LLC
Decatur, Georgia, United States, 30033
Georgia Neurology and Sleep Medicine Associates
Suwanee, Georgia, United States, 30024
United States, Indiana
Josephson Wallack Munshower Neurology P.C.
Indianapolis, Indiana, United States, 46256
United States, New Jersey
Advanced Memory Research of NJ PC
Toms River, New Jersey, United States, 08755
United States, New York
Albany Medical College
Albany, New York, United States, 12208
UBMD Neurology
Buffalo, New York, United States, 14203
Richmond Behavioral Associates
Staten Island, New York, United States, 10312
United States, North Carolina
Alzheimer's Memory Center
Charlotte, North Carolina, United States, 28270
United States, Ohio
Neuroscience Research Center, LLC
Canton, Ohio, United States, 44718
Valley Medical Research
Centerville, Ohio, United States, 45459
The Lindner Research Center
Cincinnati, Ohio, United States, 45219
Neurology Diagnostics Inc.
Dayton, Ohio, United States, 45459
Neuro-Behavioral Clinical Research, Inc.
North Canton, Ohio, United States, 44321
United States, Oklahoma
IPS Research Company
Oklahoma City, Oklahoma, United States, 73106
Tulsa Clinical Research LLC
Tulsa, Oklahoma, United States, 74136
United States, Oregon
Neural Net Research
Portland, Oregon, United States, 97225
United States, South Carolina
CBRI - Roper Hospital
Charleston, South Carolina, United States, 29414
Coastal Neurology
Port Royal, South Carolina, United States, 29935
United States, Virginia
Re:Cognition Health
Fairfax, Virginia, United States, 22031
United States, Washington
Kingfisher Cooperative, LLC
Spokane, Washington, United States, 99202
Universal Research Group, LLC
Tacoma, Washington, United States, 98405
Belgium
Cliniques Universitaires Saint-Luc
Bruxelles, Belgium, 1200
Canada, British Columbia
Okanagan Clinical Trials, Ltd.
Kelowna, British Columbia, Canada, V1Y 1Z9
Canada, Ontario
Memory Clinic (Ottawa)
Ottawa, Ontario, Canada, K1Z 1G3
Canada, Quebec
Clinique Mémoire de l'Outaouais
Gatineau, Quebec, Canada, J8T 8J1
Canada
Alpha Recherche Clinique
Québec, Canada, G3K 2P8
France
CHU Bordeaux - Pellegrin
Bordeaux, France, 33076
Hôpital Neurologique Pierre Wertheimer
Bron, France, 69677
CHU de Limoges
Limoges, France, 87042
Timone Adults Hospital
Marseille, France, 13385
Guidechauliac Hospital
Montpellier, France, 34295
Hôpital Laënnec - CHU de Nantes
Nantes, France, 44093
CHU de Rennes
Rennes, France, 35009
CRC Gerontopole Cite de la Sante, Hôpital La Grave
Toulouse, France, 31059
Hopital des Charpennes
Villeurbanne, France, 69100
Italy
IRCCS Centro S. Giovanni di Dio Fatebenefratelli
Brescia, Italy, 25125
Foundation Institute G.Giglio
Cefalù, Italy, 90015
Azienda Ospedaliera San Gerardo - Clinica Neurologica
Monza, Italy, 20900
Istituto Neurologico Casimiro Mondino, IRCCS
Pavia, Italy, 27100
University of Perugia, Ospedale S.M. della Misericordia
Perugia, Italy, 06156
Ospedale San Giovanni Calibita Fatebenefratelli
Roma, Italy, 00186
Azienda Ospedaliera Sant'Andrea
Roma, Italy, 00189
IRCCS Fondazione Santa Lucia
Rome, Italy, 00179
Clinica Neurologica Santa Maria della Misericordia
Udine, Italy, 33100
Poland
Podlaskie Centrum Psychogeriatrii
Bialystok, Poland, 15-756
Centrum Medyczne NEUROMED
Bydgoszcz, Poland, 85-163
NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
Katowice, Poland, 40-123
Indywidualna Praktyka Lekarska
Lublin, Poland, 20-582
NZOZ Neuro-Kard
Poznań, Poland, 61-853
Euromedis Sp. z o.o.
Szczecin, Poland, 70-111
Centrum Medyczne NeuroProtect
Warszawa, Poland, 01-684
Spain
Hospital General de Catalunya
Barcelona, Spain, 08195
Hospitales de Madrid
Madrid, Spain, 28015
Hospital Universitario 12 de Octubre
Madrid, Spain, 28041
Hospital Universitario QuironSalud Madrid
Madrid, Spain, 28223
Centro de salud de San Juan, Unidad de Investigación Neurociencias
Salamanca, Spain, 37005
Hospital Virgen de la Macarena
Sevilla, Spain, 41009
Hospital Universitario Mutua Terrassa
Terrassa, Spain, 08222
Hospital Universitario Doctor Peset
Valencia, Spain, 46017
United Kingdom
Re:Cognition Health
Birmingham, United Kingdom, B16 8LT
Glasgow Memory Clinic Ltd
Glasgow, United Kingdom, G20 0XA
Re:Cognition Health
Guildford, United Kingdom, GU2 7YD
Re:Cognition Health - Central London
London, United Kingdom, W1G 9JF
Re:Cognition Health
Plymouth, United Kingdom, PL6 8BT
Sponsors and Collaborators
TauRx Therapeutics Ltd
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Responsible Party: TauRx Therapeutics Ltd
ClinicalTrials.gov Identifier: NCT03446001    
Other Study ID Numbers: TRx-237-039
First Posted: February 26, 2018    Key Record Dates
Last Update Posted: September 23, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Methylene Blue
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action