XanaMIA: Effect of 10 mg Xanamem on Dementia Due to Alzheimer's Disease
Study Details
Study Description
Brief Summary
Xanamem® is being developed as a potential treatment for symptomatic, early stages of Alzheimer's Disease (AD) and Major Depressive Disorder (MDD).
This XanaMIA Phase 2b study is to investigate the safety, tolerability, and efficacy of Xanamem in in mild or moderate dementia due to AD. Trial participants will be randomized to either receive 10mg of Xanamem once daily or a placebo for 36 weeks at a 1:1 ratio in a double-blinded fashion.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 10 mg Xanamem 10 mg Xanamem tablet, to be administered orally once every morning with or without food |
Drug: Xanamem
Xanamem drug product is formulated as an immediate-release film-coated tablet formulation for oral administration. Each Xanamem tablet contains 10 mg Xanamem (UE2343) drug substance and excipients.
Other Names:
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Placebo Comparator: Placebo Placebo tablet, to be administered orally once every morning with or without food |
Drug: Placebo
Matching placebo which is identical in appearance to the test product (10 mg Xanamem once daily) except that it contains no active ingredient.
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Outcome Measures
Primary Outcome Measures
- Effects of 10 mg Xanamem on cognition [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to end of treatment (EOT) in a custom global cognitive test battery (CTB). The global CTB is calculated as an average Z-score, with higher scores indicating improvement.
- Incidence and severity of treatment-emergent adverse events (TEAEs) [safety and tolerability of Xanamem] [36 weeks (Baseline to Week 36 [EOT])]
Incidence and severity of TEAEs
- Incidence of SAEs and suspected unexpected serious adverse reactions (SUSARs) [safety and tolerability of Xanamem] [36 weeks (Baseline to Week 36 [EOT])]
Incidence of SAEs and SUSARs
Secondary Outcome Measures
- Effects of Xanamem on integrated cognitive and functional abilities [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in the Clinical Dementia Ratio - Sum of Boxes (CDR-SB)
- Effects of Xanamem on early impairment of daily functioning due to cognitive decline [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT on the Amsterdam Instrumental Activities of Daily Living Questionnaire - short version (A-IADL-Q-SV). Each question is given a score from 1 to 5, with higher scores indicating a better outcome.
- Effects of Xanamem on attention and working memory [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in an Attention Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.
- Effects of Xanamem on executive function [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in an Executive Function Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.
- Effects of Xanamem on episodic memory [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in an Episodic Memory Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.
- Effects of Xanamem on paper and pencil tests of cognition (visual attention and executive function) [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in Trail Making A and B Tests, measured as time taken to complete (seconds). Higher scores indicate a worse outcome.
- Effects of Xanamem on biomarkers of AD. [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in plasma AD biomarkers. Biomarkers to be assessed are: p-tau181, p-tau217, amyloid-beta 1-40, amyloid-beta 1-42, neurofilament light, glial fibrillary acidic protein (all pg/mL).
- Effects of Xanamem on AD biomarker ratios [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in ratios of plasma AD biomarkers: amyloid-beta 1-42/1-40 and p-tau181/amyloid-beta 1-42.
- Effects of Xanamem on neuropsychiatric symptoms of AD [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT on the Neuropsychiatric Inventory (NPI) and its component scores. A total score is calculated from the frequency and severity of each behavior. Higher scores indicate a worse outcome.
- Effects of Xanamem using clinicians' and participant/trial partner's global impression measures [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in the Clinician's Global Impression of Severity Scale (CGI-S). Assessment is made on a seven-point scale, with a higher score indicating a worse outcome.
- Effects of Xanamem using clinicians' and participant/trial partner's global impression measures [36 weeks (Baseline to Week 36 [EOT])]
Change from Baseline to EOT in the participant/trial partner's scores in the Patient's Global Impression of Change (PGI-C). Assessment is made on a seven-point scale, with a higher score indicating a worse outcome.
Other Outcome Measures
- Sparse PK sampling for use in PPK analysis [36 weeks (Baseline to Week 36 [EOT])]
Plasma Xanamem concentration (ng/mL)
- On-treatment visit PK data to assess compliance [36 weeks (Baseline to Week 36 [EOT])]
Plasma Xanamem concentration (ng/mL)
- Collection of urine for metabolite screening [36 weeks (Baseline to Week 36 [EOT])]
Identification of potential urine metabolites of Xanamem
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female aged 50 years or older, inclusive at the time of Screening.
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Clinical syndrome of mild or moderate dementia, likely to be due to AD in the opinion of the Investigator, at Screening, including meeting the following criteria:
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Clinical Dementia Rating (CDR) global score of 0.5 to 1.0
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Mini-mental state examination (MMSE) score of 18 to 26
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Magnetic resonance imaging (MRI) or computerized tomography (CT) scan within 1 year prior to randomization that excludes alternative diagnoses for dementia such as large stroke, likely vascular dementia, brain tumor, subdural hematoma, or other non-AD dementia type findings
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Positive plasma AD biomarker signature at Pre-screening, comprising fasting levels of p-tau181 ≥ 6.7 pg/mL per the Quanterix Simoa assay or equivalent levels using a comparable immunoassay.
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Cognitive impairment on a symbol coding test of at least 0.5 standard deviations (SD) below the normative data at Screening.
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If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to Screening.
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Has a consenting trial partner who, in the Investigator's judgment, has frequent and sufficient contact with the participant to be able to provide accurate information as to the participant's cognitive and functional abilities. The trial partner must be available to provide information to the Investigator and trial site staff about the participant and agrees to attend all trial site visits in person for scale completion. A trial partner should be available for the duration of the trial. The measure of adequate availability will be at the Investigator's discretion.
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Participants must be able to comfortably abstain from caffeine intake for 4 hours prior to scheduled cognitive assessments.
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Smokers are eligible if they are able to comfortably abstain from nicotine / tobacco products for 2 hours prior to scheduled cognitive assessments.
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Must provide written informed consent to participate in the trial and be willing and able to participate for the maximum of 9 months of treatment and up to 11.5 months of site visits.
Exclusion Criteria:
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Use of anti-amyloid or anti-tau antibody within 6 months.
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Diagnosis of a non-AD dementia including traumatic brain injury.
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Diagnosis of an active major mental illness of concern in the opinion in the Investigator, including major depressive disorder, bipolar illness, or schizophrenia.
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Participation in another clinical trial of a drug or device
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Has a body mass index or body weight that will interfere with participation in the trial, including inadequate venous access to complete the trial assessments, to be determined at the discretion of the Investigator.
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Previous clinically significant systemic illness or infection, including test positive COVID-19, within the past 4 weeks prior to Screening.
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Clinical diagnosis of Type I or Type II diabetes requiring insulin.
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Exhibit physical, cognitive, or language impairments, in the opinion of the Investigator, of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
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Trial participants with evidence of current infection with HIV, hepatitis B, or hepatitis C.
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Participants with a history of clinically significant drug abuse or addiction in the past 2 years
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Evidence or history of alcohol abuse
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | St Vincent's Hospital Sydney | Darlinghurst | New South Wales | Australia | |
2 | Southern Neurology | Kogarah | New South Wales | Australia | |
3 | KaRa Minds | Macquarie Park | New South Wales | Australia | |
4 | Central Coast Neurosciences Research | Tumbi Umbi | New South Wales | Australia | |
5 | The Prince Charles Hospital | Chermside | Queensland | Australia | |
6 | Austin Health | Ivanhoe | Victoria | Australia | |
7 | HammondCare | Malvern | Victoria | Australia | |
8 | Australian Alzheimer's Research Foundation | Nedlands | Western Australia | Australia | |
9 | Neurodegenerative Disorders Research | West Perth | Western Australia | Australia |
Sponsors and Collaborators
- Actinogen Medical
Investigators
- Study Director: Harinder Chera, Actinogen Medical Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ACW0009