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

• ClinicalTrials.gov Identifier: NCT05657691
• Recruitment Status: Active, not recruiting
• First Posted: December 20, 2022
• Last Update Posted: April 25, 2024
• Sponsor: Actinogen Medical
• Collaborator: AXIOM Real Time Metrics
• Information provided by (Responsible Party): Actinogen Medical

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 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.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; MDD; Cognitive Impairment	Drug: Xanamem™; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: placebo-controlled, parallel-group, double-blind, proof-of-concept trial
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: November 28, 2022
• Estimated Primary Completion Date: July 15, 2024
• Estimated Study Completion Date: July 15, 2024

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Efficacy of Xanamem on attention, including working memory [ Time Frame: 6 Weeks (Baseline to Week 6 (end of treatment (EOT))) ]
   Change from Baseline to EOT in an Attention Composite of a Cognitive Test Battery (CTB) (Detection, Identification, and One Back tests)
2. Evaluation of the short-term safety and tolerability of Xanamem [ Time Frame: 6 Weeks (Baseline to Week 6 (EOT)) ]
   Incidence and severity of treatment-emergent adverse events (TEAEs) Incidence of serious adverse events (SAEs) and SUSARs

Secondary Outcome Measures :

1. Determine the effects of Xanamem on depressive symptoms [ Time Frame: 6 Weeks (Baseline to Week 6 (EOT)) ]

   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Australia, New South Wales

Paratus Clinical Research Western Sydney

Blacktown, New South Wales, Australia

Genesis Research Services

Newcastle, New South Wales, Australia

Australia, Queensland

Paratus Clinical Research Brisbane

Brisbane, Queensland, Australia

USC Clinical Trials

Sippy Downs, Queensland, Australia

Australia, Victoria

Ramsay Clinic Albert Road

Melbourne, Victoria, Australia, 3004

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, Australia

NeuroCentrix

Noble Park, Victoria, Australia

United Kingdom

St Pancras Clinical Research

London, United Kingdom, EC2Y 8EA

Clerkenwell Health

London, United Kingdom, W1G 8DR

MAC Clinical Research - Manchester

Manchester, United Kingdom, M13 9NQ

Glasgow Memory Clinic

Motherwell, United Kingdom, ML1 4UF

MAC Clinical Research - South Yorkshire

Tankersley, United Kingdom, S75 3DL

Sponsors and Collaborators

Actinogen Medical

AXIOM Real Time Metrics

More Information

Additional Information:

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

• Responsible Party: Actinogen Medical
• ClinicalTrials.gov Identifier: NCT05657691
• Other Study ID Numbers: ACW0008
• First Posted: December 20, 2022
• Last Update Posted: April 25, 2024
• Last Verified: April 2024

• 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

Keywords provided by Actinogen Medical:

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

Additional relevant MeSH terms:

Depressive Disorder; Depression; Cognitive Dysfunction; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms; Cognition Disorders; Neurocognitive Disorders