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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.

Tracking Information
First Submitted Date  ICMJE December 24, 2018
First Posted Date  ICMJE January 1, 2019
Last Update Posted Date January 1, 2019
Actual Study Start Date  ICMJE July 3, 2018
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 31, 2018)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 31, 2018)
  • 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
  • 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
  • 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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: December 31, 2018)
  • 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
  • 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
  • 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
  • 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
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE ANAVEX2-73 for Treatment of Early Alzheimer's Disease
Official Title  ICMJE 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)
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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE 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
Condition  ICMJE Alzheimer Disease
Intervention  ICMJE
  • Drug: High dose ANAVEX2-73
    Oral capsule
  • Drug: Mid dose ANAVEX2-73
    Oral capsule
  • Drug: Placebo oral capsule
    Oral capsule
Study Arms  ICMJE
  • Experimental: High dose ANAVEX2-73
    High dose active once daily orally
    Intervention: Drug: High dose ANAVEX2-73
  • Experimental: Mid dose ANAVEX2-73
    Mid dose active once daily orally
    Intervention: Drug: Mid dose ANAVEX2-73
  • Placebo Comparator: Placebo oral capsule
    Placebo dose once daily orally
    Intervention: Drug: Placebo oral capsule
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 31, 2018)
450
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 60 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Study Director 844-689-3939 alz@anavex.com
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03790709
Other Study ID Numbers  ICMJE ANAVEX2-73-AD-004
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Anavex Life Sciences Corp.
Study Sponsor  ICMJE Anavex Life Sciences Corp.
Collaborators  ICMJE Anavex Australia Pty Ltd.
Investigators  ICMJE Not Provided
PRS Account Anavex Life Sciences Corp.
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP