Effect of 10 mg Xanamem on Dementia Due to Alzheimer's Disease (XanaMIA)

A Phase 2b/3, Double-Blind, Placebo-Controlled, Parallel-Group, 36-Week, 2-Arm Trial With an Open-Label Extension Phase to Assess the Safety, Tolerability, and Efficacy of Xanamem® 10 mg Daily in Patients With Mild or Moderate Dementia Due to Alzheimer's Disease

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/3 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. Participants who have completed the main trial will be eligible to participate in an open-label phase, which involves treatment with 10mg Xanamem once daily for a treatment period of up to a maximum of 108 weeks. The OLE is intended to finish when all participants have completed at least 60 weeks of treatment and a follow-up visit 4 weeks later.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Dementia, Mild; Dementia Moderate
• Intervention / Treatment: Drug: Xanamem; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 247
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia
      • ACW Investigative Site 106
    • Erina, New South Wales, Australia
      • ACW Investigative Site 103
    • Kogarah, New South Wales, Australia
      • ACW Investigative Site 102
    • Macquarie Park, New South Wales, Australia
      • ACW Investigative Site 107
    • Newcastle, New South Wales, Australia
      • ACW Investigative Site 111
  • Queensland
    • Birtinya, Queensland, Australia
      • ACW Investigative Site 113
    • Chermside, Queensland, Australia
      • ACW Investigative Site 105
  • South Australia
    • Bedford Park, South Australia, Australia
      • ACW Investigative Site 114
    • Woodville South, South Australia, Australia
      • ACW Investigative Site 110
  • Victoria
    • Carlton, Victoria, Australia
      • ACW Investigative Site 115
    • Ivanhoe, Victoria, Australia
      • ACW Investigative Site 101
    • Malvern, Victoria, Australia
      • ACW Investigative Site 108
    • Parkville, Victoria, Australia
      • ACW Investigative Site 112
  • Western Australia
    • Nedlands, Western Australia, Australia
      • ACW Investigative Site 104
    • West Perth, Western Australia, Australia
      • ACW Investigative Site 109
• United States
  • California
    • Carlsbad, California, United States, 92011
      • ACW Investigative Site 218
    • Orange, California, United States, 92866
      • ACW Investigative Site 213
    • Sherman Oaks, California, United States, 91403
      • ACW Investigative Site 209
  • Colorado
    • Denver, Colorado, United States, 80218
      • ACW Investigative Site 211
    • Englewood, Colorado, United States, 80113
      • ACW Investigative Site 208
  • Florida
    • Delray Beach, Florida, United States, 33445
      • ACW Investigative Site 203
    • Miami, Florida, United States, 33176
      • ACW Investigative site 201
    • New Port Richey, Florida, United States, 34652
      • ACW Investigative site 202
    • Orlando, Florida, United States, 32803
      • ACW Investigative site 204
    • The Villages, Florida, United States, 32162
      • ACW Investigative site 205
  • Georgia
    • Decatur, Georgia, United States, 30030
      • ACW Investigative Site 207
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • ACW Investigative Site 206
  • New York
    • Albany, New York, United States, 12208
      • ACW Investigative Site 214
    • Staten Island, New York, United States, 10314
      • ACW Investigative Site 219
  • Ohio
    • Dayton, Ohio, United States, 45459
      • ACW Investigative Site 210
    • Independence, Ohio, United States, 44131
      • ACW Investigative Site 217
  • Oregon
    • Portland, Oregon, United States, 97225
      • ACW Investigative Site 212
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • ACW Investigative Site 216
  • Texas
    • Austin, Texas, United States, 78757
      • ACW Investigative Site 220
  • Washington
    • Bellevue, Washington, United States, 98007
      • ACW Investigative Site 215

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female aged 50 years or older, inclusive at the time of Screening.

• 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:

  1. Clinical Dementia Rating (CDR) global score of 0.5 to 1.0
  2. Mini-mental state examination (MMSE) score of 18 to 26
  3. 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
  4. Positive plasma AD biomarker signature at Pre-screening, comprising fasting levels of a tau species protein.
• If receiving symptomatic AD medications, the dosing regimen must have been stable for 3 months prior to Screening.
• 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.
• Participants must be able to comfortably abstain from caffeine intake for 4 hours prior to scheduled cognitive assessments.
• Smokers are eligible if they are able to comfortably abstain from nicotine / tobacco products for 2 hours prior to scheduled cognitive assessments.
• 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:

• Use of anti-amyloid or anti-tau antibody within 6 months.
• Diagnosis of a non-AD dementia including traumatic brain injury.
• Diagnosis of an active major mental illness of concern in the opinion in the Investigator, including major depressive disorder, bipolar illness, or schizophrenia.
• Participation in another clinical trial of a drug or device
• 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.
• Previous clinically significant systemic illness or infection, including test positive COVID-19, within the past 4 weeks prior to Screening.
• Clinical diagnosis of Type I or Type II diabetes requiring insulin.
• 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.
• Trial participants with evidence of current infection with HIV, hepatitis B, or hepatitis C.
• Participants with a history of clinically significant drug abuse or addiction in the past 2 years
• Evidence or history of alcohol abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: UE2343
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.
Experimental: Open label phase; Participants enrolled in the open-label phase after the main trial will receive 10 mg Xanamem, 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: UE2343

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent adverse events (TEAEs) [safety and tolerability of Xanamem]	Incidence and severity of TEAEs	36 weeks
Effects of 10 mg Xanamem on integrated cognitive and functional abilities	Change from Baseline to end of treatment (EOT) in the Clinical Dementia Ratio - Sum of Boxes (CDR-SB). The CDR-SB is calculated as an average score, with lower scores indicating improvement.	36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Xanamem on integrated cognitive and functional abilities	Change from Baseline to EOT in the Clinical Dementia Ratio - Sum of Boxes (CDR-SB)	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on early impairment of daily functioning due to cognitive decline	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.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on attention and working memory	Change from Baseline to EOT in an Attention Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on executive function	Change from Baseline to EOT in an Executive Function Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on episodic memory	Change from Baseline to EOT in an Episodic Memory Composite. Scores are calculated as an average Z-score, with higher scores indicating improvement.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on paper and pencil tests of cognition (visual attention and executive function)	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.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on AD biomarker ratios	Change from Baseline to EOT in ratios of plasma AD biomarkers: amyloid-beta 1-42/1-40 and p-tau181/amyloid-beta 1-42.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on neuropsychiatric symptoms of AD	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.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem using clinicians' and participant/trial partner's global impression measures	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.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem using clinicians' and participant/trial partner's global impression measures	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.	36 weeks (Baseline to Week 36 [EOT])
Effects of Xanamem on biomarkers of AD.	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).	36 weeks (Baseline to Week 36 [EOT])

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sparse PK sampling for use in PPK analysis	Plasma Xanamem concentration (ng/mL)	36 weeks (Baseline to Week 36 [EOT])
On-treatment visit PK data to assess compliance	Plasma Xanamem concentration (ng/mL)	36 weeks (Baseline to Week 36 [EOT])
Collection of urine for metabolite screening	Identification of potential urine metabolites of Xanamem	36 weeks (Baseline to Week 36 [EOT])

Collaborators and Investigators

• Sponsor: Actinogen Medical
• Investigators: Study Director: Global Program Lead, Actinogen Medical Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): February 1, 2028

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: November 5, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 21, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Cortisol; Actinogen; Xanamem; emestedastat
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Neurocognitive Disorders; Tauopathies; Neurodegenerative Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Hemic and Lymphatic Diseases; Alzheimer Disease; Lymphoma, Follicular; Dementia; UE2343
• Other Study ID Numbers: ACW0009

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No