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ANAVEX2-73 for Treatment of Early Alzheimer's Disease

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ClinicalTrials.gov Identifier: NCT03790709
Recruitment Status : Recruiting
First Posted : January 1, 2019
Last Update Posted : January 1, 2019
Sponsor:
Collaborator:
Anavex Australia Pty Ltd.
Information provided by (Responsible Party):
Anavex Life Sciences Corp.

Brief Summary:
Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and function after 48 weeks of daily treatment. Additional outcome measures include refined measures of sleep, behavioral and psychological symptoms typically observed in AD, changes in daily functioning of participants and changes in caregiver burden, as well as changes in quality of life measures of both, patients and caregivers during treatment with ANAVEX2-73.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Drug: High dose ANAVEX2-73 Drug: Mid dose ANAVEX2-73 Drug: Placebo oral capsule Phase 2 Phase 3

Detailed Description:
This is a Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and function after 48 weeks of daily treatment. Additional outcome measures include refined measures of sleep, behavioral and psychological symptoms typically observed in AD, changes in daily functioning of participants and changes in caregiver burden, as well as changes in quality of life measures of both, patients and caregivers during treatment with ANAVEX2-73. In addition, safety assessments, pharmacokinetic (PK) assessments and collections of CSF and blood markers of AD pathophysiology before and after treatment will be performed.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 450 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: There will be blinding procedures for this study. Capsules will be indistinguishable from active ingridient containing capsules.
Primary Purpose: Treatment
Official Title: A Phase 2b/3, Double-Blind, Randomized, Placebo-Controlled 48-week Safety and Efficacy Trial of ANAVEX2-73 for the Treatment of Early Alzheimer's Disease (AD)
Actual Study Start Date : July 3, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : March 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: High dose ANAVEX2-73
High dose active once daily orally
Drug: High dose ANAVEX2-73
Oral capsule

Experimental: Mid dose ANAVEX2-73
Mid dose active once daily orally
Drug: Mid dose ANAVEX2-73
Oral capsule

Placebo Comparator: Placebo oral capsule
Placebo dose once daily orally
Drug: Placebo oral capsule
Oral capsule




Primary Outcome Measures :
  1. ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition) [ Time Frame: 48 weeks ]
    Change from baseline to week 48 in cognition according to the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog) compared to placebo

  2. ADCS-ADL (Activities of Daily Living) [ Time Frame: 48 weeks ]
    Changes from baseline to week 48 in ability to perform daily activities according to the Activities of Daily Living Scale (ADCS-ADL) compared to placebo


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: 48 weeks ]
    Assess the safety and tolerability of ANAVEX2-73 compared to placebo

  2. CDR-SB (Clinical Dementia Rating Scale Sum of Boxes) [ Time Frame: 48 weeks ]
    Change from baseline to week 48 on Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) compared to placebo

  3. RSCAQ sleep score [ Time Frame: Weeks 0, 4, 12, 24, 36, and 48 ]
    To evaluate whether ANAVEX2-73 improves sleep continuity as assessed on a serial basis (weeks 0, 4, 12, 24, 36, and 48) with a questionnaire that assess reported sleep continuity (RSCAQ)


Other Outcome Measures:
  1. Number of participants with change of brain volume assessed by MRI [ Time Frame: 48 weeks ]
    Structural (and optional ASL) MRI scan assessments characteristic for AD pathophysiology from baseline and compared to placebo at +48 weeks

  2. Blood assessment [ Time Frame: 48 weeks ]
    Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration

  3. CSF assessment [ Time Frame: 48 weeks ]

    Changes in CSF parameters (Abeta40, Abeta42, T-tau, P-tau, NFL, YKL-40, neurogranin, BACE1 concentration) characteristic for AD pathophysiology from baseline and compared to placebo at

    +48 weekstreatment differences within subgroups will be performed


  4. Number of participants with pre-specified genetic variants [ Time Frame: 48 weeks ]
    AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   60 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged 60 to 85 years, inclusive, with a NIA-AA diagnosis of mild cognitive impairment (MCI) due to AD or early stage mild dementia due to AD. AD diagnosis should be made by an appropriately qualified medical specialist and AD pathology should be confirmed by either:

    1. Historical records of amyloid CSF assessment or
    2. Historical records of amyloid PET scan or
    3. If neither historical records are available, then AD pathological diagnosis confirmation should be offered at screening:

    i. CSF collection or ii. Amyloid PET iii. Past medical records of MRI or CT are optional.

  • Mini Mental State Examination (MMSE) score between 20-28, inclusive.
  • Free Recall score ≤17 or Total Recall score <40 on the Free and Cued Selective Reminding Test (FCSRT).
  • Participants are either outpatients, or residents of an assisted-living facility. Participant has a designated study partner, who spends at least 10hrs per week with the participant, in order that assessments e.g. carer burden instruments are completed with true knowledge of the participant.
  • No suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 3 months (i.e. active suicidal thought(s) with intent but without specific plan, or active suicidal thought(s) with plan and intent) OR suicidal behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior).
  • Confirmation from the participant that, if of childbearing potential is not pregnant through urine pregnancy testing.

Exclusion Criteria:

  • Patients who have a progressive medical or neurological condition that in the opinion of the investigator would interfere with the conduct of the study. Exception: If diagnosed with seizures, must be on stable anti-seizure medication for at least 3 months prior to screening.
  • Current clinically significant systemic illness that is likely to result in deterioration of the patient's condition or affect the patient's safety during the study.
  • History or clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque.
  • History of neurologic (e.g. stroke, traumatic brain injury) or psychiatric condition that the investigator deems may interfere with interpretability of data.
  • History of untreated thyroid disorder, Type 1 diabetes, and insulin dependent or uncontrolled Type II diabetes, as determined by the investigator (e.g. non-insulin-controlled Type II diabetes, whose HbA1c value is higher than 8.0%).
  • Body Mass Index (BMI) > 30.
  • History of clinical hepatic dysfunction.
  • Current symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hematological or hormonal disorders.
  • Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase above 3x upper limit of normal (ULN) as determined during screening.
  • Significant history of drug addiction (with the exception of nicotine dependence) or abuse (including alcohol, as defined in DSM-V or in the opinion of the investigator) within the last two years prior to informed consent, or a positive urine drug screen for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at screening. Prescription medication yielding a positive drug screen are acceptable except for tricyclic antidepressants (e.g. Amitriptyline, Amoxapine, Desipramine, (Norpramin) Doxepin, Imipramine (Tofranil), Nortriptyline (Pamelor), Protriptyline (Vivactil), Trimipramine (Surmontil)).
  • Clinically significant infection within the last 30 days prior screening (e.g., chronic persistent or acute infection, urinary tract infections (UTI)).
  • Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for asthma are permitted) or chemotherapeutic agents for malignancy within the last 3 years.
  • Myocardial infarction within the last year.
  • History of cancer within the last 3 years, with the exception of basal cell carcinoma and non-metastatic squamous cell carcinoma of the skin and prostate cancer with currently normal PSA.
  • Other clinically significant abnormality on physical, neurological, laboratory, or electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise the study or be detrimental to the participant.
  • Hemoglobin < 11 g/dL.
  • Have any contraindication to MRI scanning, including cardiac pacemaker/defibrillator, ferromagnetic metal implants (e.g., in skull and cardiac devices or severe claustrophobia).
  • Smoking > 1 pack of cigarettes per day (as assessed for the 30 days prior to screening).
  • Alcohol use of more than 2 drinks per day.
  • Current use of over-the-counter (OTC) supplements or nutraceuticals unless they are on stable dose for at least 3 months prior to screening and are documented in the eCRF.
  • Use of over the counter (OTC) or prescription medication for sleep on 2 or more occasions per week.
  • Being treated with psychoactive medications on a stable dose for less than 3 month.
  • Any prior exposure to ANAVEX2-73.
  • Individuals enrolled in previous AD clinical trial involving an investigational drug treatment less than 3 months ago (longer than 3 month ago allowed).
  • Any known hypersensitivity to any of the excipients contained in the study drug formulation.
  • Any other criteria (such as a clinically significant screening blood test result), which in the opinion of the Investigator causes the participant not to qualify for the study.
  • Evidence of cerebrovascular dementia with a Hachinski score of 4 or more.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03790709


Contacts
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Contact: Study Director 844-689-3939 alz@anavex.com

Locations
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Australia, New South Wales
Hornsby (Northern Sydney Health) Recruiting
Hornsby, New South Wales, Australia
Contact: Susan Kurrle, Prof         
KaRa MINDS Recruiting
Macquarie Park, New South Wales, Australia
Contact: Rosalyn Lai, Dr         
Australia, South Australia
The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH) Recruiting
Adelaide, South Australia, Australia
Contact: Cathy Short, Dr         
Australia, Victoria
Penninsula Therapeutic and Research Group Recruiting
Frankston, Victoria, Australia
Contact: Jennifer Grunfeld, Dr         
Geelong Private Medical Centre Recruiting
Geelong, Victoria, Australia
Contact: Alastair Mander, A/Prof         
Delmont Private Hospital Recruiting
Glen Iris, Victoria, Australia
Contact: Peter Drysdale, Dr         
Hammond Care Recruiting
Malvern, Victoria, Australia
Contact: Stephen Macfarlane, A/Prof         
Royal Melbourne Hospital (RMH) Recruiting
Parkville, Victoria, Australia
Contact: Amy Brodtmann, A/Prof         
Australia, Western Australia
McCusker Recruiting
Nedlands, Western Australia, Australia
Contact: Roger Clarnette, A/Prof         
Sponsors and Collaborators
Anavex Life Sciences Corp.
Anavex Australia Pty Ltd.

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Responsible Party: Anavex Life Sciences Corp.
ClinicalTrials.gov Identifier: NCT03790709     History of Changes
Other Study ID Numbers: ANAVEX2-73-AD-004
First Posted: January 1, 2019    Key Record Dates
Last Update Posted: January 1, 2019
Last Verified: December 2018

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

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