CompletedPhase 3Results posted

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

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

Lead sponsor

TauRx Therapeutics Ltd

Asset

LMTM

Listed sites

103

Recruiting sites

Enrollment

598

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD•Amyloid biomarker required (PET)•CDR global 0.5-2•MMSE 16-27•Study partner/caregiver required

Primary endpoints

•ADAS-Cog•ADCS-Activities of Daily Living (ADCS-ADL)•Number of Study Participants With Serious

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03446001

Org study IDTRx-237-039

Timeline

Milestones

Study start2017-12-01actual

Study first posted2018-02-26actual

Primary completion2022-03-31actual

Study completion2023-04-04actual

Last update posted2025-09-04actual

Results first posted2025-09-04actual

Assets

Drug assets

LMTM

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (26)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other (unclassified)

Safety / tolerability / PK

Global cognition

Function / daily living

Global cognition

4 endpoints

Secondary/protocol endpoint

Change in Standardized Uptake Value Ratio (SUVR) Based on Temporal Lobe 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Secondary/protocol endpoint

Change in Standardized Uptake Value Ratio (SUVR) Based on Temporal Lobe 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) (8 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Secondary/registry result

Change in Standardized Uptake Value Ratio (SUVR) Based on Temporal Lobe 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), ratio	Reported bounds
Controln=88 Participants	-0.025	--0.036 - -0.015
TRx0237 16 mg/Dayn=93 Participants	-0.026	--0.036 - -0.016

Secondary/registry result

Change in Standardized Uptake Value Ratio (SUVR) Based on Temporal Lobe 18F-fluorodeoxyglucose Positron Emission Tomography (18F-FDG-PET) (8 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), ratio	Reported bounds
Controln=88 Participants	-0.027	--0.038 - -0.016
TRx0237 8 mg/Dayn=22 Participants	-0.022	--0.041 - -0.002

Function / daily living

4 endpoints

Primary/protocol endpoint

Change From Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) (16 mg/Day vs Control)

Time frame:52 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Primary/registry result

Change From Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) (16 mg/Day vs Control)

Time frame:52 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Reported bounds
Controln=204 Participants	-0.77	--2.32 - 0.78
TRx0237 16 mg/Dayn=191 Participants	-0.62	--2.19 - 0.95

Secondary/protocol endpoint

Change From Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) (8 mg/Day vs Control)

Time frame:52 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline on Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) (8 mg/Day vs Control)

Time frame:52 weeks

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Reported bounds
Controln=204 Participants	-0.82	--2.36 - 0.72
TRx0237 8 mg/Dayn=47 Participants	-1.41	--4.46 - 1.64

Safety / tolerability / PK

6 endpoints

Primary/protocol endpoint

Number of Study Participants With Serious and Non-serious Adverse Events (16 mg/Day vs Control)

Time frame:52 weeks

event count, event

Primary/registry result

Number of Study Participants With Serious and Non-serious Adverse Events (16 mg/Day vs Control)

Time frame:52 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
ControlNumber of study participants with serious adverse eventsn=266 Participants	17	-
Number of study participants with non-serious adverse eventsn=266 Participants	146	-
TRx0237 16 mg/DayNumber of study participants with serious adverse eventsn=252 Participants	18	-
Number of study participants with non-serious adverse eventsn=252 Participants	131	-

Secondary/protocol endpoint

Number of Study Participants With Serious and Non-serious Adverse Events (8 mg/Day vs Control)

Time frame:52 weeks

event count, event

Secondary/protocol endpoint

Number of Study Participants With Serious and Non-serious Adverse Events (Open-label)

Time frame:104 weeks

event count, event

Secondary/registry result

Number of Study Participants With Serious and Non-serious Adverse Events (8 mg/Day vs Control)

Time frame:52 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
ControlNumber of study participants with serious adverse eventsn=266 Participants	17	-
Number of study participants with nonserious adverse eventsn=266 Participants	146	-
TRx0237 8 mg/DayNumber of study participants with serious adverse eventsn=80 Participants	6	-
Number of study participants with nonserious adverse eventsn=80 Participants	47	-

Secondary/registry result

Number of Study Participants With Serious and Non-serious Adverse Events (Open-label)

Time frame:104 weeks

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Control to TRx0237 16 mg/DayNumber of study participants with serious adverse eventsn=201 Participants	14	-
Number of study participants with nonserious adverse eventsn=201 Participants	88	-
TRx0237 (Either Dose) to TRx0237 16 mg/DayNumber of study participants with serious adverse eventsn=248 Participants	13	-
Number of study participants with nonserious adverse eventsn=248 Participants	101	-

Other (unclassified)

12 endpoints

Primary/protocol endpoint/low confidence

Change From Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) (16 mg/Day vs Control)

Time frame:52 weeks

ADAS-Cog

change from baseline, improvement

Primary/registry result/low confidence

Change From Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) (16 mg/Day vs Control)

Time frame:52 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Reported bounds
Controln=198 Participants	1.71	-0.69 - 2.73
TRx0237 16 mg/Dayn=189 Participants	1.34	-0.32 - 2.36

Secondary/protocol endpoint/low confidence

Change in Annualized Rate of Whole Brain Atrophy (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in Annualized Rate of Temporoparietal Lobe Atrophy (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) (8 mg/Day vs Control)

Time frame:52 weeks

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in Annualized Rate of Temporoparietal Lobe Atrophy (8 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Open-Label Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)

Time frame:104 weeks

ADAS-Cog

descriptive

Secondary/registry result/low confidence

Change in Annualized Rate of Whole Brain Atrophy (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mm3/year	Reported bounds
Controln=175 Participants	-11137.44	--12682.86 - -9592.01
TRx0237 16 mg/Dayn=165 Participants	-11162.70	--12711.43 - -9613.98

Secondary/registry result/low confidence

Change in Annualized Rate of Temporoparietal Lobe Atrophy (16 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mm3/year	Reported bounds
Controln=175 Participants	-740.79	--821.39 - -660.19
TRx0237 16 mg/Dayn=165 Participants	-711.14	--791.96 - -630.32

Secondary/registry result/low confidence

Change From Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) (8 mg/Day vs Control)

Time frame:52 weeks

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	Reported bounds
Controln=198 Participants	1.78	-0.79 - 2.77
TRx0237 8 mg/Dayn=47 Participants	1.06	--0.89 - 3.01

Secondary/registry result/low confidence

Change in Annualized Rate of Temporoparietal Lobe Atrophy (8 mg/Day vs Control)

Time frame:52 weeks

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mm3/year	Reported bounds
Controln=175 Participants	-729.55	--806.00 - -652.09
TRx0237 8 mg/Dayn=45 Participants	-651.28	--799.33 - -503.24

Secondary/registry result/low confidence

Change From Open-Label Baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11)

Time frame:104 weeks

ADAS-Cog

descriptive

Posted result

Group	Value (least_squares_mean), score on a scale	Reported bounds
Control to TRx0237 16 mg/Dayn=146 Participants	2.98	-2.01 - 3.95
TRx0237 (Either Dose) to TRx0237 16 mg/Dayn=179 Participants	3.58	-2.70 - 4.47

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.