Xanamem® in Adults With Major Depressive Disorder and Impaired Cognition (XanaCIDD)

NCT05657691 | Completed Phase 2 DMC

• 1 other identifier: ACW0008
• Study Type: interventional
• Target: 167
• Locations: 2 countries
• Sites: 12

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 XanaCIDD Phase II study in MDD is to investigate the safety and efficacy of Xanamem™ in treating patients with cognitive and depressive symptoms. Trial participants will be randomized to either receive 10mg of Xanamem™ once daily or a Placebo at a 1:1 ratio in a double-blinded fashion.

Conditions

Major Depressive Disorder; MDD; Cognitive Impairment

Keywords

Xanamem; UE2343; Actinogen; Cortisol; 11β-HSD1; 11-beta-Hydroxysteroid Dehydrogenase Type 1; emestedastat

Outcome Measures

Primary Outcomes (2)

• Efficacy of Xanamem on attention, including working memory

  Change from Baseline to EOT in an Attention Composite of a Cognitive Test Battery (CTB) (Detection, Identification, and One Back tests)

  6 Weeks (Baseline to Week 6 (end of treatment (EOT)))

• Evaluation of the short-term safety and tolerability of Xanamem

  Incidence and severity of treatment-emergent adverse events (TEAEs) Incidence of serious adverse events (SAEs) and SUSARs

  6 Weeks (Baseline to Week 6 (EOT))

Secondary Outcomes (1)

• Determine the effects of Xanamem on depressive symptoms

  6 Weeks (Baseline to Week 6 (EOT))

Study Arms (2)

10 mg Xanamem™

EXPERIMENTAL

10 mg Xanamem™ capsule, to be administered orally once every morning with or without food

Drug: Xanamem™

Placebo

PLACEBO COMPARATOR

Placebo capsule, to be administered orally once every morning with or without food

Drug: Placebo

Interventions

Xanamem™ DRUG

Xanamem™ is formulated in green and cream-colored size 3, Coni-Snap-shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains the active pharmaceutical ingredient of UE2343.

Also known as: UE2343

10 mg Xanamem™

Placebo DRUG

Matching placebo which is identical in appearance to the test product (10 mg Xanamem™ QD) except that it contains no active ingredient.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 to 75, inclusive.
• Positive MDD primary diagnosis confirmed by the Mini-International Neuropsychiatric Interview (MINI).
• Persistent depressive symptoms as determined by a Hamilton Depression Rating Scale (HAM-D) ≥ 17 at Screening.
• Cognitive abilities on a coding test \> 0.5 standard deviations below expected.
• Self-reported subjective cognitive dysfunction.
• Currently or previously treated with a stable dose of a first- or second-line antidepressant that is approved for the treatment of depression (but not a tricyclic antidepressant, monoamine oxidase inhibitor, or vortioxetine). If on current treatment, dose must be stable for at least 6 weeks.
• Smokers are eligible if they are able to comfortably abstain from nicotine for 2 hours prior to scheduled cognitive assessments.
• Able to comfortably abstain from caffeine intake for 4 hours prior to scheduled cognitive assessments.
• Must provide written informed consent to participate in the trial and be willing and able to comply with the requirements of the protocol and complete all trial visits.

You may not qualify if:

• Active suicidal ideation within the previous 3 months
• On a tricyclic antidepressant, monoamine oxidase inhibitor, esketamine, or vortioxetine.
• A history of clinically diagnosed dementia of any type
• Previous clinically significant systemic illness or infection, including test positive COVID-19, within the past 4 weeks prior to Screening
• Has a BMI or body weight that will interfere with participation in the trial
• Type I or Type II diabetes requiring insulin
• Clinically significant ECG abnormalities
• Participation in another clinical trial of a drug or device
• Trial participants who in the opinion of the Investigator exhibit physical, cognitive, or language impairments of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.
• Positive testing for HIV, hepatitis B surface antigen, or hepatitis C antibodies at Screening.
• Participants with a history of drug abuse or addiction in the past 2 years
• Current use of cannabis/marijuana, or tetrahydrocannabinol-containing medications.

Sponsors & Collaborators

• Actinogen Medical: lead
• AXIOM Real Time Metrics: collaborator

Study Sites (12)

Paratus Clinical Research Western Sydney

Blacktown, New South Wales, Australia

Location

Genesis Research Services

Newcastle, New South Wales, Australia

Location

Paratus Clinical Research Brisbane

Brisbane, Queensland, Australia

Location

USC Clinical Trials

Sippy Downs, Queensland, Australia

Location

Ramsay Clinic Albert Road

Melbourne, Victoria, 3004, Australia

Location

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, Australia

Location

NeuroCentrix

Noble Park, Victoria, Australia

Location

St Pancras Clinical Research

London, EC2Y 8EA, United Kingdom

Location

Clerkenwell Health

London, W1G 8DR, United Kingdom

Location

MAC Clinical Research - Manchester

Manchester, M13 9NQ, United Kingdom

Location

Glasgow Memory Clinic

Motherwell, ML1 4UF, United Kingdom

Location

MAC Clinical Research - South Yorkshire

Tankersley, S75 3DL, United Kingdom

Location

Related Links

• Selection and early clinical evaluation of the brain-penetrant 11β-HSD1 inhibitor UE2343

MeSH Terms

Conditions

Depressive Disorder, Major; Cognitive Dysfunction

Interventions

UE2343

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: placebo-controlled, parallel-group, double-blind, proof-of-concept trial

Study Record Dates

• First Submitted: October 17, 2022
• First Posted: December 20, 2022
• Study Start: November 28, 2022
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: January 22, 2025

Record last verified: 2025-01

Locations

AU (7); GB (5)