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

Alzheimer Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03446001
• Other study ID #: TRx-237-039
• Status: Completed
• Phase: Phase 3
• Start date: January 10, 2018
• Est. completion date: April 4, 2023

Study information

• Verified date: May 2023
• Source: TauRx Therapeutics Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 598
• Est. completion date: April 4, 2023
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• TRx0237 16 mg/day
Oral TRx0237 4-mg tablets administered twice daily
• Placebo
Oral placebo tablets (some of which contain a urinary discolorant) administered twice daily
• TRx0237 8 mg/day
Oral TRx0237 4-mg tablet administered twice daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
TauRx Therapeutics Ltd

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Italy,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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