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

XanaCIDD: a Double-Blind, Randomized, Placebo Controlled, Parallel-Group Trial to Assess the Safety, Tolerability, and Efficacy of Xanamem® in Adults with Major Depressive Disorder and Impaired Cognition

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.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Major Depressive Disorder; MDD
• Intervention / Treatment: Drug: Xanamem™; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 167
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia
      • Paratus Clinical Research Western Sydney
    • Newcastle, New South Wales, Australia
      • Genesis Research Services
  • Queensland
    • Brisbane, Queensland, Australia
      • Paratus Clinical Research Brisbane
    • Sippy Downs, Queensland, Australia
      • USC Clinical Trials
  • Victoria
    • Melbourne, Victoria, Australia
      • Monash Alfred Psychiatry Research Centre
    • Melbourne, Victoria, Australia, 3004
      • Ramsay Clinic Albert Road
    • Noble Park, Victoria, Australia
      • NeuroCentrix
• United Kingdom
  • London, United Kingdom, EC2Y 8EA
    • St Pancras Clinical Research
  • London, United Kingdom, W1G 8DR
    • Clerkenwell Health
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research - Manchester
  • Motherwell, United Kingdom, ML1 4UF
    • Glasgow Memory Clinic
  • Tankersley, United Kingdom, S75 3DL
    • MAC Clinical Research - South Yorkshire

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 mg Xanamem™; 10 mg Xanamem™ capsule, to be administered orally once every morning with or without food	Drug: Xanamem™; 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.; Other Names: UE2343
Placebo Comparator: Placebo; Placebo capsule, 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™ QD) except that it contains no active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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))
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)))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the effects of Xanamem on depressive symptoms	Change from Baseline to EOT on the Montgomery-Åsberg Depression Rating Scale (MADRS). The MADRS is a 10-item diagnostic questionnaire used to assess the severity of depressive episodes and is designed to be sensitive to treatment effects. Each item is scored from 0 to 6, and overall scores range from 0 to 60. Higher scores indicate greater severity.	6 Weeks (Baseline to Week 6 (EOT))

Collaborators and Investigators

• Sponsor: Actinogen Medical
• Collaborators: AXIOM Real Time Metrics
• Investigators: Study Director: Harinder Chera, Actinogen Medical Limited

Publications and helpful links

General Publications

• Webster SP, McBride A, Binnie M, Sooy K, Seckl JR, Andrew R, Pallin TD, Hunt HJ, Perrior TR, Ruffles VS, Ketelbey JW, Boyd A, Walker BR. Selection and early clinical evaluation of the brain-penetrant 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitor UE2343 (Xanamem). Br J Pharmacol. 2017 Mar;174(5):396-408. doi: 10.1111/bph.13699. Epub 2017 Jan 25.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: December 11, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 20, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Cortisol; Actinogen; Xanamem; UE2343; 11β-HSD1; 11-beta-Hydroxysteroid Dehydrogenase Type 1; emestedastat
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Neurocognitive Disorders; Cognition Disorders; Mood Disorders; Cognitive Dysfunction; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: ACW0008

Drug and device information, study documents

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