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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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MDD, Major Depressive Disorder, Cognitive Impairment

Intervention / Treatment
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* Drug: Xanamem™
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: placebo-controlled, parallel-group, double-blind, proof-of-concept trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg Xanamem™<br>10 mg Xanamem™ capsule, to be administered orally once every morning with or without food | Drug: Xanamem™<br>* 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.<br>* Other names: UE2343;|
| Placebo Comparator: Placebo<br>Placebo capsule, to be administered orally once every morning with or without food | Drug: Placebo<br>* Matching placebo which is identical in appearance to the test product (10 mg Xanamem™ QD) except that it contains no active ingredient.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Xanamem on attention, including working memory | Change from Baseline to EOT in an Attention Composite of a Cogstate 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 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)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: A customized Cognitive Test Battery (CTB) will be used to assess the extent to which 10 mg Xanamem once daily improves performance in multiple cognitive domains (attention, executive function, and episodic memory) from Baseline to each trial visit compared to placebo. The assessments require the participant to perform a variety of digital tasks: Detection (Psychomotor Function) Identification (Attention) One Back (Working Memory) One Card Learning (Visual Learning) International Digit Symbol Substitution Test - Symbols (Processing Speed) | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: Hopkins Verbal Learning Test-Revised (HVLT-R), a list-learning test that will be used to assess the extent to which Xanamem sustains performance in verbal learning and memory (recognition and recall). A higher number of correct answers indicates a better result. | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: Category Fluency Test (CFT) to measure performance in language and executive function domains. The CFT measures the spontaneous production of words that are exemplars of different categories (such as animals, fruits, and vegetables) in 1 minute. A higher number of correct answers indicates a better result. | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: Letter Fluency Test (LFT) to measure performance in language and executive function domains. The LFT measures spontaneous productions of words beginning with a designated letter (3 different letters are assessed, such as F, A, and S) in 1 minute. A higher number of correct answers indicates a better result. | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: MADRS, 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 more severe depression. | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales | Determining the durability of cognitive and anti-depressive effects at Week 10 (4 Weeks post last dose of Xanamem) utilising: Patient Global Impression of Severity (PGI-S), for participants to provide their perception of the severity of their symptoms observed during the trial and 4 weeks after ceasing Xanamem by rating the severity of their symptoms on a seven-point scale: A higher number indicates a higher severity. | 4 Weeks (Week 6 (EOT) to Week 10 (EOS)) | 
| Determine the responder rate of Xanamem on depressive symptoms | Percentage of participants achieving a 50% or greater reduction in MADRS score Percentage of participants achieving a MADRS score of < 10 points at Week 6 (EOT) | 6 Weeks (Baseline to Week 6 (EOT)) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Xanamem, UE2343, Actinogen, Cortisol, 11β-HSD1, 11-beta-Hydroxysteroid Dehydrogenase Type 1