Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment
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| ClinicalTrials.gov Identifier: NCT03446001 |
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Recruitment Status :
Completed
First Posted : February 26, 2018
Last Update Posted : May 24, 2023
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Sponsor:
TauRx Therapeutics Ltd
Information provided by (Responsible Party):
TauRx Therapeutics Ltd
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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 ...
| 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 |
| Actual Primary Completion Date : | March 31, 2022 |
| Actual Study Completion Date : | April 4, 2023 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Alzheimer disease
MedlinePlus related topics:
Alzheimer's Disease
| 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 :
- 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).
- 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).
- 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 :
- 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.
- 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.
- 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.
- 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).
- 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).
- 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).
- 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.
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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
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Sponsors and Collaborators
TauRx Therapeutics Ltd
| 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: | May 24, 2023 |
| Last Verified: | May 2023 |
| 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 |