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A Phase II Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to AD (XanADu) (XanADu)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Actinogen Medical
Sponsor:
Collaborator:
ICON Clinical Research
Information provided by (Responsible Party):
Actinogen Medical
ClinicalTrials.gov Identifier:
NCT02727699
First received: March 21, 2016
Last updated: March 22, 2017
Last verified: March 2017
  Purpose
This XanADu Phase II study in mild Alzheimer's Disease (AD) is to assess the safety, tolerability and efficacy of Xanamem™ in subjects with mild dementia due to Alzheimer's Disease. Subjects will be randomized to receive either 10mg once daily Xanamem™ or Placebo at a 1:1 ratio in a double-blinded fashion.

Condition Intervention Phase
Dementia
Drug: Xanamem™
Drug: Placebo (for Xanamem™)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
Official Title: XanADu: A Phase II, Double-Blind, 12-Week, Randomised, Placebo-Controlled Study to Assess the Safety, Tolerability and Efficacy of Xanamem™ in Subjects With Mild Dementia Due to Alzheimer's Disease (AD)

Resource links provided by NLM:


Further study details as provided by Actinogen Medical:

Primary Outcome Measures:
  • AD COMposite Scores [ Time Frame: Baseline, Week 12 ]
    Change in AD COMposite Scores (ADCOMs, composite data derived from Alzheimer's Disease Assessment Scales - Cognitive Subscale Version 14 [ADAS-Cog v14], Clinical Dementia Rating Scale - Sum of Boxes [CDR-SOB], and Mini-Mental Status Examination [MMSE])

  • ADAS-Cog v14 [ Time Frame: Baseline, Week 12 ]
    Change in Alzheimer's Disease Assessment Scales - Cognitive Subscale Score, version 14 (ADAS-Cog v14)


Secondary Outcome Measures:
  • RAVLT [ Time Frame: Baseline, Week 12 ]
    Change in Rey Auditory Verbal Learning Test (RAVLT)

  • CDR-SOB [ Time Frame: Screening, Baseline, Week 12 ]
    Change in Clinical Dementia Rating Scale - Sum of Boxes (CDR-SOB)

  • MMSE [ Time Frame: Screening, Baseline, Week 12 ]
    Change in Mini-Mental Status Examination (MMSE)

  • NPI [ Time Frame: Baseline, Week 12 ]
    Change in Neuropsychiatric Inventory (NPI)

  • NTB - Executive Domain [ Time Frame: Baseline, Week 12 ]
    Change in Neuropsychological Test Batteries (NTB). Only the NTB tests which are known measures of executive function features were selected for the current study.


Other Outcome Measures:
  • Clinical Safety Laboratory Values [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Clinical Safety Laboratory Values (biochemistry, haematology, urine examination)

  • AEs [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Ad Hoc ]
    Incidence of Adverse Events (AEs)

  • ECG [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Electrocardiogram (ECG) Values

  • CSSRS [ Time Frame: Screening, Week 4, Week 8, Week 12, Week 16 ]
    Change in Scores of Columbia Suicide Severity Rating Scale (CSSRS)

  • Metabolic Function [ Time Frame: Baseline, Week 12 ]
    Change in Metabolic Function Test Results of Lipids, Glucose, Haemoglobin A1c (HbA1c)

  • Vital Signs [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Unscheduled Safety Visit ]
    Change in Vital Signs (including Heart Rate, Blood Pressure, Body Weight and BMI)

  • NFM [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16 ]
    Change in Nerve Function Monitoring (NFM)

  • NTSS-6 [ Time Frame: Screening, Baseline, Week 4, Week 8, Week 12, Week 16, Ad Hoc and Unscheduled Safety Visit ]
    Change in Neuropathy Total Symptom Score (NTSS-6)

  • PK [ Time Frame: Baseline, Week 4, Week 8, Week 12 and Unscheduled Safety Visit ]
    Change in Pharmacokinetics (PK)

  • Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of adrenocorticotropic hormone (ACTH) [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  • Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of dehydroepiandrosterone Sulfate (DHEAS) [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  • Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of Androstenedione [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit

  • Optional PD Assessment - Changes in Pharmacodynamic (PD) measures of Testosterone [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16 ]
    This assessment will be carried out on 50 subjects who consented to this optional test. PD sample will be collected at pre-dose at each required visit


Estimated Enrollment: 174
Anticipated Study Start Date: March 23, 2017
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Xanamem™
Oral Xanamem™ capsules 10mg, to be administered once daily
Drug: Xanamem™
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
Other Name: UE2343
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 (for Xanamem™)
Excipient blend capsules manufactured to mimic Xanamem™ capsules
Other Name: Placebo

Detailed Description:

This is a Phase II, randomised, multi-centre, double-blind, placebo-controlled proof-of-concept study to assess the safety, tolerability and efficacy of oral Xanamem™ once daily in adult subjects with mild dementia due to AD.

Based on Xanamem™'s mode of action on hippocampal function, amnestic symptoms may respond best, thus favouring the inclusion of mild dementia due to AD, with given evidence of disease progression. Subjects will be treated in a double-blind fashion, where both the investigators and subjects will be unaware of the treatment assignments, to minimise any subjective or unrecognised bias carried by the investigators and subjects. Placebo will be used as the comparator in this study. In this study, Xanamem™ will be administered in conjunction with current standard therapy.

It is planned to randomise approximately 174 subjects at approximately 20 study sites in three countries (Australia, United Kingdom, and United States), with the aim to enrol 7 to 10 subjects at each study site. Subject enrolment will be competitive but a cap of 18 subjects per study site is to be established to avoid any site effects. In case the sample composition at one study site is creating concerns, an enrolment stop can also occur at fewer than 18 subjects.

The data safety monitoring board (DSMB) will periodically meet for the review of accumulating safety study data.

At the Baseline visit (Week 0), eligible subjects will be randomised on a 1:1 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 4 and Week 8, 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 AE.

Subjects will be interviewed and examined at the study site at each visit, and will complete a variety of questionnaires and routine safety evaluations.

Optional PD sampling will be performed at specific visits. 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 one to 4 weeks, a double-blind treatment period of 12 weeks, and a follow-up period of 4 weeks. The total duration of the study is expected to be 2 years.

  Eligibility

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females aged 50 years or older at the time of informed consent.
  2. Female Subjects:

    1. For post-menopausal women, if there is any clinical concern about the menopausal status, this should be confirmed by an follicle-stimulating hormone (FSH) test.
    2. Pre-menopausal women must have a negative pregnancy test at Screening and Baseline and be willing to use two effective methods of contraception simultaneously (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from the Screening visit until 3 months after last dose of study drug.
    3. Are surgically sterilised or have had a hysterectomy.
  3. Male Subjects:

    a. Who are willing to use two effective methods of contraception simultaneously (unless anatomically sterile or where abstaining from sexual intercourse is in line with the preferred and usual lifestyle of the subject) from Day 1 until 3 months after last dose of study drug.

  4. Diagnosis of mild dementia due to Alzheimer's disease (AD) with increased level of certainty (provided by evidence of clinical deterioration within the 6 months preceding Screening, as assessed by the investigator) as determined by the National Institute of Ageing (NIA) and the Alzheimer's Association (AA) workgroup.
  5. Mild dementia due to probable AD with MMSE 20 to 26 (inclusive).
  6. Clinical Dementia Rating Scale (CDR) Global Score of 0.5 to 1.0.
  7. A brain magnetic resonance imaging (MRI) or computed tomography (CT) scan in the 12 months preceding Screening that in the investigator's opinion is consistent with AD as the principle aetiology of the dementia with no other clinically significant abnormality, e.g. another principle underlying aetiology of the subject's dementia, or a lesion which could affect cognition e.g. a brain tumour or large stroke.
  8. On stable dose of acetylcholinesterase (AChEI) and/or memantine (at least 3 months prior to Screening) OR treatment-naïve. Initiating AChEIs or memantine during the study will not be permitted.
  9. Apart from a clinical diagnosis of mild dementia due to AD, the subject must be in good health as determined by the investigator, based on medical history and screening assessments.
  10. Has a consenting study partner who, in the investigator's judgement, has frequent and sufficient contact with the subject to be able to provide accurate information as to the subject's cognitive and functional abilities. The study partner must be available to provide information to the investigator and study site staff about the subject and agrees to attend all study site visits in person for scale completion. A study partner should be available for the duration of the study. The measure of adequate availability will be at the investigator's discretion.
  11. Must be willing and able to comply with the requirements of the protocol and must be available to complete the study.
  12. Must satisfy a medical examiner about their fitness to participate in the study.
  13. Must provide written informed consent to participate in the study.

Exclusion Criteria:

  1. Clinically significant abnormalities in vital signs (blood pressure, heart rate, respiration rate and oral temperature), as determined by the investigator.
  2. Clinically significant abnormal haematology, biochemistry and urine examination values, specifically abnormal liver and renal function and Vitamin B12 levels below lower threshold since these parameters may impact cognitive function, as determined by the investigator.
  3. Has had a significant systematic illness or infection within the past 4 weeks prior to randomisation, as determined by the investigator.
  4. Clinically significant neurological disease other than AD, such as (but not limited to) Parkinson's disease, multi-infarct dementia, Huntington's disease, normal pressure hydrocephalus, brain tumour, progressive supranuclear palsy, seizure disorder, subdural haematoma, multiple sclerosis or a history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
  5. Subjects with clinical evidence of peripheral neuropathy or historical evidence of clinically significant nerve conduction abnormalities.
  6. Has had a stroke within the year prior to randomisation, as determined by the investigator.
  7. Has a lifetime diagnosis of a major psychiatric disorder (other than dementia), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. This includes but is not limited to schizophrenia, schizoaffective disorder, bipolar affective disorder, alcohol dependence syndrome or major depressive disorder.
  8. Clinically significant ECG abnormalities, including Fredericia corrected QTc interval (QTcF) > 450 msec, following ECG tracings at Screening.
  9. Use of any prohibited medication as detailed in the study protocol.
  10. Participation in another clinical study of a drug or device whereby the last investigational drug/device administration is within 60 days of Screening.
  11. Inability to communicate well with the investigator (i.e. language problem, non-fluent English [as scales will be provided in English only], poor mental development or impaired cerebral function).
  12. Subject will undergo the tests, ADAS-Cog v14, CDR-SOB, MMSE, NTB (executive domain) and RAVLT 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.
  13. Subject has ingested any food or drink containing grapefruit, Seville oranges, star fruit or derived products (e.g. fruit juice), for at least 3 days prior to the first administration of study drug.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02727699

Contacts
Contact: Vincent Ruffles +61 2 8964 7401 Vincent.Ruffles@actinogen.com.au
Contact: Kerrie Boyd +61 2 8964 7401 Kerrie.Boyd@actinogen.com.au

Locations
United States, Georgia
Atlanta Center for Medical Research Recruiting
Atlanta, Georgia, United States, 30331
Contact: Maria K Atella    404-881-5800    matella@acmr.org   
Principal Investigator: Robert A Riesenberg, MD         
Australia, New South Wales
Central Coast Neurosciences Research Recruiting
East Gosford, New South Wales, Australia, 2250
Contact: Michelle Anderson    +61243249811    michelle@neurosciences.com.au   
Principal Investigator: Jonathan W Sturm, MD         
Sub-Investigator: Denis S Crimmins, Asst Prof         
Sponsors and Collaborators
Actinogen Medical
ICON Clinical Research
Investigators
Study Chair: Vincent Ruffles Actinogen Medical
Study Director: Alan Boyd, MD, FFPM Actinogen Medical
  More Information

Publications:
Responsible Party: Actinogen Medical
ClinicalTrials.gov Identifier: NCT02727699     History of Changes
Other Study ID Numbers: ACW0002
Study First Received: March 21, 2016
Last Updated: March 22, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

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

Keywords provided by Actinogen Medical:
Mild Dementia
Actinogen
Alzheimer's Disease
Xanamem
Cortisol
UE2343
XanADu

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on March 24, 2017