Xanamem™ in Healthy Elderly Subjects

NCT03830762 | Completed Phase 1 DMC

• 1 other identifier: ACW0003
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

Xanamem™ is being developed as a potential drug for 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 Alzheimer's disease. The XanaHES study is testing the safety and tolerability of Xanamem. It is planned to enrol approximately 84 participants, male and female aged from 50 to 75 who are in good health, in the study at 1 centre in Australia. The XanaHES Phase I study is a single-blind study. Subjects will be randomised to receive either 20mg once daily Xanamem or Placebo in cohort 1. Once all subjects have completed the study treatment of 12 weeks, a dose escalation committee will decide if a new cohort, cohort 2, with 30mg once daily vs placebo is started.

Conditions

Safety; Peripheral Neuropathy; Cortisol; Central Nervous System; Cognitive Function; Healthy Ageing; Small Fibre Neuropathy; Cerebrospinal Fluid; Electrocardiography

Keywords

Actinogen; Xanamem; UE2343; Cortisol; 11β-HSD1; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Healthy Ageing; Peripheral Neuropathy; Safety; Dose Escalation; Elderly; XanaHES; emestedastat

Outcome Measures

Primary Outcomes (11)

• Incidence of Treatment-Emergent Adverse Events (AEs)

  The number, type, and severity of treatment-emergent adverse events (AEs) that are reported from Screening Visit to Follow-up Visit will be collected and evaluated.

  20 Weeks (Screening up to Week 16 Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Incidence of Clinically Significant Changes in Serum Biomarker Levels in a Standard Serum Chemistry Panel

  Collection of blood samples for clinical laboratory testing to assess any clinically significant changes in standard serum chemistry measures.

  Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Incidence of Clinically Significant Laboratory Haematological Biomarker Levels in a Standard Haematology Panel.

  Collection of blood samples for clinical laboratory testing to assess any clinically significant changes in standard haematology measures.

  Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Incidence of Clinically Significant Changes or Abnormalities Following Physical Examination

  Evaluation of any clinically significant changes or abnormalities reported following a standard Physical Examination.

  Screening up to Week 16 (Follow-Up) and Unscheduled Safety Visit throughout duration of study up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Nerve Conduction Assessments

  Nerve Conduction assessments will be used to detect presence and severity of nerve damage.

  Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Neuropathy Total Symptom Score-6 (NTSS-6)

  Changes in the Neuropathy Total Symptom Score (NTSS-6) administered by a physician to assess a subjects' medical history. Each item will also be graded for its frequency and intensity, adding up to a total score from "0" to "21.96" points. A total score of \> 6 would exclude the subject from the study.

  Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)

• Toronto Clinical Neuropathy Score (TCNS)

  Changes in Toronto Clinical Neuropathy Score (TCNS) to detect for neuropathy out of a total score of 19; scales are defined as follows: 0-5 = no neuropathy; 6-8 = mild neuropathy; 9-11 = moderate neuropathy; ≥ 12 = severe neuropathy.

  Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)

• Skin Biopsy

  A 3mm skin sample will be taken via skin punch biopsy to detect intra-epidermal nerve fiber density; this allows for the objectification and quantification of a small-fiber neuropathy.

  At Baseline and Week 12 (End of Treatment)

• Quantitative Sensory Testing (QST)

  Thermal sensory testing using Quantitative Sensory Testing (QST) for cold, warm and heat pain to detect peripheral nerve disorders.

  Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

• Columbia Suicide Severity Rating Scale (CSSRS)

  Any change in Columbia Suicide Severity Rating Scale (CSSRS) will assess suicidal ideation and behaviour. * Suicidal ideation score: Any score greater than 0 is important and may indicate the need for mental health intervention. * Suicidal ideation intensity rating: The five intensity item scores create a total score (range 0 to 25) to represent the intensity rating, if the patient did not endorse any suicidal ideation the intensity rating is 0.

  Screening, Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)

• Electrocardiogram (ECG)

  Any clinically significant electrocardiogram (ECG) abnormalities will be recorded, including corrected QT interval (QTc) of \> 500 msec.

  Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

Other Outcomes (9)

• Detection Test (Cogstate Test Battery)

  Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)

• Identification Test (Cogstate Test Battery)

  Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)

• One Back Working Memory Test (Cogstate Test Battery)

  Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)

Study Arms (2)

Cohort 1 / Cohort 2 (Active)

EXPERIMENTAL

20mg or 30mg capsules of Xanamem respectively, to be administered PO once daily.

Drug: Xanamem

Cohort 1 / Cohort 2 (Placebo)

PLACEBO COMPARATOR

Matching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily.

Drug: Matching Placebo

Interventions

Xanamem DRUG

Oral Xanamem capsules 20mg or 30mg, administered PO once daily. Xanamem is formulated in green and cream coloured size 3, Coni-Snap shaped gelatin capsules as an excipient blend at a dose of 10mg. It contains active pharmaceutical ingredient of UE2343.

Also known as: UE2343

Cohort 1 / Cohort 2 (Active)

Matching Placebo DRUG

Matching placebo which is identical in appearance to the test product (20mg, 30mg Xanamem™ QD) except that it contains no active ingredient.

Also known as: Placebo

Cohort 1 / Cohort 2 (Placebo)

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Volunteers aged 50 to 75 years.
• Female subjects:
• Post-menopausal women, defined as no menses for 12 months without an alternative medical cause. If there is any concern about the menopausal status of a prospective female subject, a follicle stimulating hormone test (FSH) should be requested to confirm post-menopausal status. Post-menopausal women confirmed by FSH level \> 40 mIU/mL, will be confirmed by the local laboratory.
• Women of childbearing potential (WOCBP) must have a negative pregnancy test.
• Male Subjects:
• Who are sexually active, fertile men must use highly effective methods of contraception from Day 1 until 3 months after last dose of study drug if their partners are WOCBP
• Who are permanently sterile or have had bilateral orchiectomy or bilateral vasectomy.
• No disease which may cause a peripheral neuropathy.
• No 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).
• Must provide written informed consent to participate in the study and be willing and able to participate for the maximum of 12 weeks of treatment and 16 weeks of site visits.

You may not qualify if:

• Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
• Body Mass Index (BMI) \> 38 kg/m2
• Clinically significant abnormal haematology, biochemistry and urine examination values, as determined by the investigator.
• Participants who have a history of liver disease, including fatty liver, or LFT elevations requiring investigation will not be eligible.
• Has had a significant systemic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator.
• Documented diagnosis of Type I or Type II diabetes.
• Has a history of disease directly related to the hypothalamus, the pituitary and/or the adrenal glands which affects the hypothalamic-pituitary-adrenal axis function.
• Has any uncontrolled clinical condition relating to glucose or lipid metabolism.
• Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities. Clinical evidence of neuropathy.
• Clinically significant electrocardiogram (ECG) abnormalities, including QTc interval \> 450 msec (male) and \> 470 msec (female), following ECG tracings at Screening.
• Use of any prohibited medication.
• Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days of Screening.
• Inability to communicate well with the investigator (i.e. language problem, non-fluent English \[as questionnaires and study drug label will be provided in English only\], poor mental development or impaired cerebral function).
• Subject will undergo the Columbia Suicide Severity Rating Scale (CSSRS), Toronto Clinical Neuropathy Score (TCNS), EuroQoL Health Related Quality of Life - 5 Dimensions - 5 Levels (EQ-5D-5L), and Cogstate Test Battery at the indicated time-points to avoid uncontrolled learning effects. Subjects who need to perform these tests externally to and in parallel with this study will be excluded.
• For subjects that consent, and are subsequently accepted for enrolled into, the CSF optional sub-study, subjects must have no contraindications to the lumbar puncture procedure as assessed by the Principal Investigator. Such contraindications may include uncontrolled bleeding abnormalities or skin or spine abnormalities.

Sponsors & Collaborators

• Actinogen Medical: lead
• ICON plc: collaborator

Study Sites (1)

Linear Clinical Research

Perth, Western Australia, 6009, Australia

Location

Related Publications (1)

• 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.

  PMID: 28012176 BACKGROUND

MeSH Terms

Conditions

Peripheral Nervous System Diseases; Small Fiber Neuropathy

Interventions

UE2343

Condition Hierarchy (Ancestors)

Neuromuscular Diseases; Nervous System Diseases

Study Officials

• Bill Ketelbey, MD

  Actinogen Medical

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Study treatment is only blinded for the trial subject.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A Dose Escalation Committee will review the results from Cohort 1 (20 mg active vs. placebo arms) and provide a recommendation to proceed with Cohort 2 (30 mg active vs. placebo arms) randomisation which involves a dose escalation.

Study Record Dates

• First Submitted: January 23, 2019
• First Posted: February 5, 2019
• Study Start: January 21, 2019
• Primary Completion: December 7, 2019
• Study Completion: January 7, 2020
• Last Updated: January 22, 2025

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)