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Xanamem™ in Healthy Elderly Subjects (XanaHES)

Primary Purpose

Safety, Peripheral Neuropathy, Cortisol

Status

Completed

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

Xanamem

Matching Placebo

About this trial

This is an interventional other trial for Safety focused on measuring Actinogen, Xanamem, UE2343, Cortisol, 11β-HSD1, 11-beta-Hydroxysteroid Dehydrogenase Type 1, Healthy Ageing, Peripheral Neuropathy, Safety, Dose Escalation, Elderly, XanaHES

Eligibility Criteria

50 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Volunteers aged 50 to 75 years.
Female subjects:
1. 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.
2. Women of childbearing potential (WOCBP) must have a negative pregnancy test.
Male Subjects:
1. 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
2. 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.

Exclusion Criteria:

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.
Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). Subjects returning a positive result will be managed by the site in line with standard care.

Sites / Locations

Linear Clinical Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cohort 1 / Cohort 2 (Active)

Cohort 1 / Cohort 2 (Placebo)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

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.

Incidence of Clinically Significant Changes or Abnormalities Following Physical Examination

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

Nerve Conduction Assessments

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

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.

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.

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.

Quantitative Sensory Testing (QST)

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

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.

Electrocardiogram (ECG)

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

Secondary Outcome Measures

Full Information

NCT ID

NCT03830762

First Posted

January 23, 2019

Last Updated

August 25, 2020

Sponsor

Actinogen Medical

Collaborators

ICON plc

1. Study Identification

Unique Protocol Identification Number

NCT03830762

Brief Title

Xanamem™ in Healthy Elderly Subjects

Acronym

XanaHES

Official Title

XanaHES: A Phase I, Single Blinded, Central Reader Blinded, Placebo-Controlled, Dose Escalation Study of Xanamem™ to Assess Safety and Tolerability in Healthy Elderly Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

August 2020

Overall Recruitment Status

Completed

Study Start Date

January 21, 2019 (Actual)

Primary Completion Date

December 7, 2019 (Actual)

Study Completion Date

January 7, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Actinogen Medical

Collaborators

ICON plc

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

Detailed Description

This is a Phase I, randomised, single-centre, single-blind, placebo-controlled study to assess the safety, tolerability of oral Xanamem once daily in healthy elderly subjects. It is planned to randomise approximately 84 subjects, 42 in each cohort, at a single site in Australia. Cohort 1 starts with a 20mg QD dose vs matching placebo. A Dose Escalation Committee will review the results from cohort 1 and provide a recommendation to proceed with Cohort 2 randomisation which involves a dose escalation to 30mg. At the Baseline visit (Week 0), eligible subjects will be randomised on a 30:12 ratio to receive either Xanamem administered orally QD (treatment group) or matching placebo (placebo group). Subjects will return to the study site for visits at Week 2, Week 4, Week 6, Week 8, Week 10, End of Treatment (Week 12) and Follow-up (4 weeks post last dose of study drug) visits, at which study assessments will be performed. Ad hoc telephone contact may also occur at any other time-point throughout the study, if deemed necessary by the investigator/study nurse, or if the subject wishes to report an adverse event (AE). Subjects will be interviewed and examined at the study site at each visit and will complete a variety of questionnaires, routine safety evaluations and nerve function tests. A central reader will review every Nerve Function Monitoring (NFM) assessment performed for each subject for Potential Nerve Safety Signals (PNSS). Optional cerebrospinal fluid (CSF) sampling will be performed at baseline and end of treatment visits for a small subgroup of subjects, who provide additional consent. Subjects who do not provide consent for this optional sub-study will still be eligible for the main study. The overall study duration for an individual subject will be 17 to 20 weeks, including a screening period of up to 4 weeks, a single-blind treatment period of 12 weeks, and a follow-up period of 4 weeks. The total duration of the study is expected to be 1.5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Model Description

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.

Masking

Participant

Masking Description

Study treatment is only blinded for the trial subject.

Allocation

Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Cohort 1 / Cohort 2 (Active)

Arm Type

Experimental

Arm Description

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

Arm Title

Cohort 1 / Cohort 2 (Placebo)

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Xanamem

Other Intervention Name(s)

UE2343

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Matching Placebo

Other Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Incidence of Treatment-Emergent Adverse Events (AEs)

Description

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.

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

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

Description

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

Time Frame

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

Title

Incidence of Clinically Significant Changes or Abnormalities Following Physical Examination

Description

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

Time Frame

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])

Title

Nerve Conduction Assessments

Description

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

Time Frame

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

Title

Neuropathy Total Symptom Score-6 (NTSS-6)

Description

Time Frame

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

Title

Toronto Clinical Neuropathy Score (TCNS)

Description

Time Frame

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

Title

Skin Biopsy

Description

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.

Time Frame

At Baseline and Week 12 (End of Treatment)

Title

Quantitative Sensory Testing (QST)

Description

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

Time Frame

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

Title

Columbia Suicide Severity Rating Scale (CSSRS)

Description

Time Frame

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

Title

Electrocardiogram (ECG)

Description

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

Time Frame

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

Other Pre-specified Outcome Measures:

Title

Detection Test (Cogstate Test Battery)

Description

Changes in Cogstate Detection test is a measure of simple reaction time and has been shown to provide a valid assessment of psychomotor function. For this test, the subject must press a "YES" response key as soon as they detect an event (i.e. a card turning face up presented in the centre of the computer screen). The software measures the response time to detect each event.

Time Frame