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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03830762




Registration number
NCT03830762
Ethics application status
Date submitted
23/01/2019
Date registered
5/02/2019
Date last updated
25/06/2019

Titles & IDs
Public title
Xanamem™ in Healthy Elderly Subjects
Scientific 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
Secondary ID [1] 0 0
ACW0003
Universal Trial Number (UTN)
Trial acronym
XanaHES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Safety 0 0
Peripheral Neuropathy 0 0
Cortisol 0 0
Central Nervous System 0 0
Cognitive Function 0 0
Healthy Ageing 0 0
Small Fibre Neuropathy 0 0
Cerebrospinal Fluid 0 0
Electrocardiography 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Xanamem
Treatment: Drugs - Matching Placebo

Experimental: Cohort 1 / Cohort 2 (Active) - 20mg or 30mg capsules of Xanamem respectively, to be administered PO once daily.

Placebo Comparator: Cohort 1 / Cohort 2 (Placebo) - Matching placebo which is identical in appearance to the test product except that it contains no active ingredient, to be administered once daily.


Treatment: Drugs: Xanamem
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.

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

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
20 Weeks (Screening up to Week 16 Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])
Primary outcome [2] 0 0
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.
Timepoint [2] 0 0
Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])
Primary outcome [3] 0 0
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.
Timepoint [3] 0 0
Screening up to Week 16 (Follow-Up [4 Weeks Post Last Dose of Study Drug ± 4 Days])
Primary outcome [4] 0 0
Incidence of Clinically Significant Changes or Abnormalities Following Physical Examination - Evaluation of any clinically significant changes or abnormalities reported following a standard Physical Examination.
Timepoint [4] 0 0
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])
Primary outcome [5] 0 0
Nerve Conduction Assessments - Nerve Conduction assessments will be used to detect presence and severity of nerve damage.
Timepoint [5] 0 0
Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])
Primary outcome [6] 0 0
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.
Timepoint [6] 0 0
Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)
Primary outcome [7] 0 0
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.
Timepoint [7] 0 0
Screening, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up) and Telephone Contact (Ad Hoc)
Primary outcome [8] 0 0
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.
Timepoint [8] 0 0
At Baseline and Week 12 (End of Treatment)
Primary outcome [9] 0 0
Quantitative Sensory Testing (QST) - Thermal sensory testing using Quantitative Sensory Testing (QST) for cold, warm and heat pain to detect peripheral nerve disorders.
Timepoint [9] 0 0
Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])
Primary outcome [10] 0 0
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.
Timepoint [10] 0 0
Screening, Baseline, Week 2, Week 4, Week 8, Week 12 (End of Treatment), Week 16 (Follow-Up)
Primary outcome [11] 0 0
Electrocardiogram (ECG) - Any clinically significant electrocardiogram (ECG) abnormalities will be recorded, including corrected QT interval (QTc) of > 500 msec.
Timepoint [11] 0 0
Screening up to Week 16 (Follow-Up Visit [4 Weeks Post Last Dose of Study Drug ± 4 Days])

Eligibility
Key inclusion criteria
1. Volunteers aged 50 to 75 years.

2. 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.

3. 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.

4. No disease which may cause a peripheral neuropathy.

5. 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).

6. 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.
Minimum age
50 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Clinically significant abnormalities in vital signs (blood pressure, heart rate,
respiration rate and oral temperature), as determined by the investigator.

2. Body Mass Index (BMI) > 38 kg/m2

3. Clinically significant abnormal haematology, biochemistry and urine examination
values, as determined by the investigator.

4. Participants who have a history of liver disease, including fatty liver, or LFT
elevations requiring investigation will not be eligible.

5. Has had a significant systemic illness or infection within the past 4 weeks prior to
randomisation, as determined by the investigator.

6. Documented diagnosis of Type I or Type II diabetes.

7. 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.

8. Has any uncontrolled clinical condition relating to glucose or lipid metabolism.

9. Subjects with clinical evidence of peripheral neuropathy or historical evidence of
clinically significant nerve conduction abnormalities. Clinical evidence of
neuropathy.

10. Clinically significant electrocardiogram (ECG) abnormalities, including QTc interval >
450 msec (male) and > 470 msec (female), following ECG tracings at Screening.

11. Use of any prohibited medication.

12. Participation in another clinical study of a drug or device whereby the last
investigational drug/device administration is within 60 days of Screening.

13. 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).

14. 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.

15. 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.

16. 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.

Study design
Purpose of the study
Other
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Linear Clinical Research - Perth
Recruitment postcode(s) [1] 0 0
6009 - Perth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Actinogen Medical
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
ICON plc
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03830762
Trial related presentations / 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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitor UE2343 (Xanamem™). Br J Pharmacol. 2017 Mar;174(5):396-408. doi: 10.1111/bph.13699. Epub 2017 Jan 25.
Public notes

Contacts
Principal investigator
Name 0 0
Bill Ketelbey, MD
Address 0 0
Actinogen Medical
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Nicola Norton
Address 0 0
Country 0 0
Phone 0 0
+61 (0) 414 416 034
Fax 0 0
Email 0 0
nnorton@linear.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03830762