A Double-Blind, Placebo-Controlled, Dose Ranging Study of Xanamem® in Healthy Elderly Volunteers (XanaMIA-DR)

• ClinicalTrials.gov Identifier: NCT04983368
• Recruitment Status: Completed
• First Posted: July 30, 2021
• Last Update Posted: April 8, 2022
• Sponsor: Actinogen Medical
• Collaborator: Avance Clinical
• Information provided by (Responsible Party): Actinogen Medical

Study Description

Brief Summary:

Xanamem® is being developed as a potential drug for Mild Cognitive Impairment in Alzheimer's disease. This study drug has been designed to change the cortisol levels in the brain. Cortisol is a naturally occurring hormone in the body. It is believed that reducing the level of cortisol will be a benefit in the treatment of Mild Cognitive Impairment in Alzheimer's disease.

The purpose of this study in older volunteers is to investigate the smallest dose of Xanamem® (5 mg or 10 mg) which works and to investigate which dose in this study will be used in the upcoming clinical trials in patients.

Condition or disease	Intervention/treatment	Phase
Mild Cognitive Impairment; Alzheimer's Disease	Drug: Xanamem® 5 mg; Drug: Placebo; Drug: Xanamem® 10 mg	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Volunteer subjects will be randomly assigned to 1 of 3 treatment groups to receive either 5 mg Xanamem®, 10 mg Xanamem® or placebo in the ratio of 1:1:1 with approximately 35 subjects in each treatment group. This sample size has been selected to allow for approximately 30 subjects per treatment group to complete the study.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Study treatment is blinded for participants, investigators.
• Primary Purpose: Treatment
• Official Title: XanaMIA-DR A Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy, Pharmacodynamics and Safety of Xanamem® in Healthy Elderly Volunteers
• Actual Study Start Date: June 30, 2021
• Actual Primary Completion Date: February 11, 2022
• Actual Study Completion Date: February 11, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Xanamem® 5 mg; Oral Xanamem® capsules 5 mg, to be administered once daily	Drug: Xanamem® 5 mg; Oral Xanamem® ("UE2343") capsules 5 mg, administered orally once daily.
Experimental: Xanamem® 10 mg; Oral Xanamem® capsules 10 mg, to be administered once daily	Drug: Xanamem® 10 mg; Oral Xanamem® ("UE2343") capsules 10 mg, administered orally once daily.
Placebo Comparator: Placebo; Matching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily.	Drug: Placebo; Matching placebo which is identical in appearance to the test product (5 mg, 10 mg Xanamem® QD) except that it contains no active ingredient.

Outcome Measures

Primary Outcome Measures :

1. Short-term efficacy: Assessment of changes of different doses of Xanamem® on cognition. [ Time Frame: Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up) ]
   Using a tailored Cogstate Neuropsychological Test Battery (NTB), changes from baseline, as well as composite scores based on a combination of these variables at each treatment visit [Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up)] will be analyzed.
2. Assessment of safety and tolerability of different Xanamem® doses by the occurrence of Treatment-Emergent Adverse Events (TEAEs). [ Time Frame: 10 Weeks [Baseline to Week 10 Follow-Up (4 Weeks Post Last Dose of Study Drug)] ]
   The number, type, and severity of Treatment-Emergent Adverse Events (TEAEs) that are reported from Baseline to Follow-up Visit will be collected and evaluated.

Secondary Outcome Measures :

1. Short-term efficacy of different doses of Xanamem® on cognition [ Time Frame: Screening, Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up) ]
   Using the International Daily Digit Symbol Substitution Test-Symbols, to analyze changes from Screening to, Baseline, Week 2, Week 4, Week 6 (End of Treatment), Week 10 (Follow-Up).

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male or female aged 50 to 80
2. Body mass index 17.5 to < 35 kg/m2, inclusive at the time of screening
3. Mini-Mental State Score of ≥ 25 points at screening
4. Must provide written informed consent

Exclusion Criteria:

1. Abnormalities in vital signs at screening or baseline
2. Clinically significant abnormal hematology or biochemistry values, as determined by the investigator at screening and/or baseline.
3. Previous clinically significant systemic illness or infection within the past 4 weeks prior to screening or baseline, as determined by the investigator
4. Clinically significant ECG abnormalities
5. Use of tobacco- or nicotine-containing products in the past month or unwillingness to abstain during study participation
6. Participation in another clinical study of a drug or device
7. Known allergy to the study drug (Xanamem®) or any of the excipients
8. Subjects who are likely to be unable to comply with the study schedule and/ or subjects with an inability to communicate well with the investigator
9. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen, or hepatitis C antibodies at screening
10. Subjects with a history of drug abuse or addiction in the past 5 years.
11. Evidence of alcohol abuse (defined as greater than 21 standard units per week for males and greater than 14 standard units per week for females)

Contacts and Locations

Locations

Australia, Australian Capital Territory

Paratus Clinical Research Canberra

Bruce, Australian Capital Territory, Australia, 2617

Australia, New South Wales

Paratus Clinical Research Western Sydney

Blacktown, New South Wales, Australia, 2148

Paratus Clinical Research Central Coast

Kanwal, New South Wales, Australia, 2259

Australia, Queensland

Paratus Clinical Research Brisbane

Albion, Queensland, Australia, 4010

USC Clinical Trials

Sippy Downs, Queensland, Australia, 4556

Sponsors and Collaborators

Actinogen Medical

Avance Clinical

Investigators

• Study Director: Miriam Roesner; Actinogen Medical Limited

More Information

Additional Information:

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

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.

• Responsible Party: Actinogen Medical
• ClinicalTrials.gov Identifier: NCT04983368
• Other Study ID Numbers: ACW0005
• First Posted: July 30, 2021
• Last Update Posted: April 8, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Actinogen Medical:

Cognitive Function; Healthy Volunteers

Additional relevant MeSH terms:

Alzheimer Disease; Cognitive Dysfunction; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders