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

Sponsor

Actinogen Medical (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05657691

Collaborator

AXIOM Real Time Metrics (Other)

160

Enrollment

Locations

Arms

18.6

Anticipated Duration (Months)

14.5

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

placebo-controlled, parallel-group, double-blind, proof-of-concept trialplacebo-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 :

Nov 28, 2022

Anticipated Primary Completion Date :

Mar 15, 2024

Anticipated Study Completion Date :

Jun 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 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.

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.

Outcome Measures

Primary Outcome Measures

Efficacy of Xanamem on attention, including working memory [6 Weeks (Baseline to Week 6 (end of treatment (EOT)))]
Change from Baseline to EOT in an Attention Composite of a Cogstate Cognitive Test Battery (CTB) (Detection, Identification, and One Back tests)
Evaluation of the short-term safety and tolerability of Xanamem [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

Determine the effects of Xanamem on depressive symptoms [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.
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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)
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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.
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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.
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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.
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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.
Determine the durability of cognitive and antidepressant response to Xanamem using cognitive and depression scales [4 Weeks (Week 6 (EOT) to Week 10 (EOS))]
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.
Determine the responder rate of Xanamem on depressive symptoms [6 Weeks (Baseline to Week 6 (EOT))]
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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Male or female aged 18 to 70, inclusive
Positive MDD primary diagnosis confirmed by the Mini-International Neuropsychiatric Interview (M.I.N.I.)
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
On 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) drug for at least 6 weeks.
BMI 17.5 to 38 kg/m2.
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
On a tricyclic antidepressant, monoamine oxidase inhibitor, 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
Type I or Type II diabetes requiring insulin.
Clinically significant ECG abnormalities
Smokers of > 5 cigarettes a day or equivalent nicotine (includes vaping) / tobacco products.
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

	Site	City	State	Country
1	Paratus Clinical Research Canberra	Canberra	Australian Capital Territory	Australia
2	Paratus Clinical Research Western Sydney	Blacktown	New South Wales	Australia
3	Emeritus Research	Botany	New South Wales	Australia
4	Paratus Clinical Research Central Coast	Kanwal	New South Wales	Australia
5	Genesis Research Services	Newcastle	New South Wales	Australia
6	Paratus Clinical Research Brisbane	Brisbane	Queensland	Australia
7	USC Clinical Trials	Sippy Downs	Queensland	Australia
8	CMAX Clinical Research	Adelaide	South Australia	Australia
9	Emeritus Research	Camberwell	Victoria	Australia
10	Monash Alfred Psychiatry Research Centre	Melbourne	Victoria	Australia
11	NeuroCentrix	Noble Park	Victoria	Australia