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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 : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
TauRx Therapeutics Ltd

Tracking Information
First Submitted Date  ICMJE February 8, 2018
First Posted Date  ICMJE February 26, 2018
Last Update Posted Date November 22, 2019
Actual Study Start Date  ICMJE January 10, 2018
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
  • Change in Standardized Uptake Value Ratio based on temporal lobe 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) [ Time Frame: Baseline and 26 weeks ]
  • Number of participants with serious and non-serious adverse events [ Time Frame: Up to 30 weeks ]
    All laboratory test or vital sign parameter abnormalities deemed clinically significant by the Investigator are to be reported as adverse events
Change History Complete list of historical versions of study NCT03446001 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2019)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2018)
  • Change in annualized rate of whole brain atrophy [ Time Frame: Baseline and 6 months ]
    Compare the annualized rate of whole brain atrophy as measured by the Boundary Shift Integral as measured by magnetic resonance imaging (MRI)
  • Change in annualized rate of atrophy in other brain regions [ Time Frame: Baseline and 6 months ]
    Compare the annualized rate of atrophy of other brain regions (including hippocampus, temporal parietal lobes and lateral ventricular volumes) as measured by MRI
  • Change in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog11) compared to imaging measures [ Time Frame: Baseline, 13 weeks and 26 weeks ]
    Examine associations between the measures of temporal, frontal and parietal lobe SUVR with ADAS-cog11
  • Change in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL23) compared to imaging measures [ Time Frame: Baseline, 13 weeks and 26 weeks ]
    Examine associations between the measures of temporal, frontal and parietal lobe SUVR with ADCS-ADL23
  • Change from Baseline on Standardized Uptake Value Ratio (using temporal lobe 18F-FDG-PET) based on the presence or absence of Apolipoprotein E4 allele in subjects by or for whom legally acceptable consent is separately provided [ Time Frame: Up to 26 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy of TRx0237 in Subjects With Alzheimer's Disease Followed by Open-Label Treatment
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: TRx0237 16 mg/day
    Oral TRx0237 4-mg tablets administered twice daily
  • Drug: Placebo
    Oral placebo tablets (some of which contain a urinary discolorant) administered twice daily
  • Drug: TRx0237 8 mg/day
    Oral TRx0237 4-mg tablet administered twice daily
Study Arms  ICMJE
  • Experimental: TRx0237 16 mg/day
    Intervention: Drug: TRx0237 16 mg/day
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
  • Experimental: TRx0237 8 mg/day
    Intervention: Drug: TRx0237 8 mg/day
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: November 15, 2019)
450
Original Estimated Enrollment  ICMJE
 (submitted: February 20, 2018)
180
Estimated Study Completion Date  ICMJE December 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
  • 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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 90 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Italy,   Poland,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03446001
Other Study ID Numbers  ICMJE TRx-237-039
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party TauRx Therapeutics Ltd
Study Sponsor  ICMJE TauRx Therapeutics Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account TauRx Therapeutics Ltd
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP