<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03790709</url>
  </required_header>
  <id_info>
    <org_study_id>ANAVEX2-73-AD-004</org_study_id>
    <nct_id>NCT03790709</nct_id>
  </id_info>
  <brief_title>ANAVEX2-73 for Treatment of Early Alzheimer's Disease</brief_title>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anavex Life Sciences Corp.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Anavex Australia Pty Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Anavex Germany GmbH</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Anavex Canada Ltd.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Anavex Life Sciences Corp.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and function&#xD;
      after 48 weeks of daily treatment. Additional outcome measures include refined measures of&#xD;
      sleep, behavioral and psychological symptoms typically observed in AD, changes in daily&#xD;
      functioning of participants and changes in caregiver burden, as well as changes in quality of&#xD;
      life measures of both, patients and caregivers during treatment with ANAVEX2-73.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2b/3 48-week study to evaluate the effects of ANAVEX2-73 on cognition and&#xD;
      function after 48 weeks of daily treatment. Additional outcome measures include refined&#xD;
      measures of sleep, behavioral and psychological symptoms typically observed in AD, changes in&#xD;
      daily functioning of participants and changes in caregiver burden, as well as changes in&#xD;
      quality of life measures of both, patients and caregivers during treatment with ANAVEX2-73.&#xD;
      In addition, safety assessments, pharmacokinetic (PK) assessments and collections of CSF and&#xD;
      blood markers of AD pathophysiology before and after treatment will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 3, 2018</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>There will be blinding procedures for this study. Capsules will be indistinguishable from active ingridient containing capsules.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ADCS-ADL (Activities of Daily Living)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)</measure>
    <time_frame>48 weeks</time_frame>
    <description>Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared with placebo using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.03</measure>
    <time_frame>48 weeks</time_frame>
    <description>Assess the safety and tolerability of ANAVEX2-73 compared to placebo</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of participants with change of brain volume assessed by MRI</measure>
    <time_frame>48 weeks</time_frame>
    <description>To evaluate the effect of ANAVEX2-73 on structural and Arterial Spin Labeling (ASL) MRI scan assessments characteristic for AD pathophysiology compared to placebo over a 48-week treatment duration</description>
  </other_outcome>
  <other_outcome>
    <measure>Blood assessment</measure>
    <time_frame>48 weeks</time_frame>
    <description>Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration</description>
  </other_outcome>
  <other_outcome>
    <measure>CSF assessment</measure>
    <time_frame>48 weeks</time_frame>
    <description>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&#xD;
+48 weekstreatment differences within subgroups will be performed</description>
  </other_outcome>
  <other_outcome>
    <measure>Number of participants with pre-specified genetic variants</measure>
    <time_frame>48 weeks</time_frame>
    <description>AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed</description>
  </other_outcome>
  <other_outcome>
    <measure>RSCAQ sleep score</measure>
    <time_frame>Weeks 0, 4, 12, 24, 36, and 48</time_frame>
    <description>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)</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">509</enrollment>
  <condition>Alzheimer Disease</condition>
  <arm_group>
    <arm_group_label>High dose ANAVEX2-73</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>High dose active once daily orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mid dose ANAVEX2-73</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mid dose active once daily orally</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo oral capsule</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo dose once daily orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose ANAVEX2-73</intervention_name>
    <description>Oral capsule</description>
    <arm_group_label>High dose ANAVEX2-73</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mid dose ANAVEX2-73</intervention_name>
    <description>Oral capsule</description>
    <arm_group_label>Mid dose ANAVEX2-73</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Oral capsule</description>
    <arm_group_label>Placebo oral capsule</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients aged 60 to 85 years, inclusive, with a NIA-AA diagnosis of mild cognitive&#xD;
             impairment (MCI) due to AD or early stage mild dementia due to AD. AD diagnosis should&#xD;
             be made by an appropriately qualified medical specialist and AD pathology should be&#xD;
             confirmed by either:&#xD;
&#xD;
               1. Historical records of amyloid CSF assessment or&#xD;
&#xD;
               2. Historical records of amyloid PET scan or&#xD;
&#xD;
               3. If neither historical records are available, then AD pathological diagnosis&#xD;
                  confirmation should be offered at screening:&#xD;
&#xD;
             i. CSF collection or ii. Amyloid PET iii. Past medical records of MRI or CT are&#xD;
             optional.&#xD;
&#xD;
          -  Mini Mental State Examination (MMSE) score between 20-28, inclusive.&#xD;
&#xD;
          -  Free Recall score ≤17 or Total Recall score &lt;40 on the Free and Cued Selective&#xD;
             Reminding Test (FCSRT).&#xD;
&#xD;
          -  Participants are either outpatients, or residents of an assisted-living facility.&#xD;
             Participant has a designated study partner, who spends at least 10hrs per week with&#xD;
             the participant, in order that assessments e.g. carer burden instruments are completed&#xD;
             with true knowledge of the participant.&#xD;
&#xD;
          -  No suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale&#xD;
             (C-SSRS) in the past 3 months (i.e. active suicidal thought(s) with intent but without&#xD;
             specific plan, or active suicidal thought(s) with plan and intent) OR suicidal&#xD;
             behavior in the past 2 years (i.e. actual attempt, interrupted attempt, aborted&#xD;
             attempt, or preparatory acts or behavior).&#xD;
&#xD;
          -  Confirmation from the participant that, if of childbearing potential is not pregnant&#xD;
             through urine pregnancy testing.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have a progressive medical or neurological condition that in the opinion&#xD;
             of the investigator would interfere with the conduct of the study. Exception: If&#xD;
             diagnosed with seizures, must be on stable anti-seizure medication for at least 3&#xD;
             months prior to screening.&#xD;
&#xD;
          -  Current clinically significant systemic illness that is likely to result in&#xD;
             deterioration of the patient's condition or affect the patient's safety during the&#xD;
             study.&#xD;
&#xD;
          -  History or clinically evident stroke or clinically significant carotid or&#xD;
             vertebrobasilar stenosis or plaque.&#xD;
&#xD;
          -  History of neurologic (e.g. stroke, traumatic brain injury) or psychiatric condition&#xD;
             that the investigator deems may interfere with interpretability of data.&#xD;
&#xD;
          -  History of untreated thyroid disorder, Type 1 diabetes, and insulin dependent or&#xD;
             uncontrolled Type II diabetes, as determined by the investigator (e.g.&#xD;
             non-insulin-controlled Type II diabetes, whose HbA1c value is higher than 8.0%).&#xD;
&#xD;
          -  Body Mass Index (BMI) &gt; 30.&#xD;
&#xD;
          -  History of clinical hepatic dysfunction.&#xD;
&#xD;
          -  Current symptomatic and unstable/uncontrolled gastrointestinal, hepatic, renal,&#xD;
             respiratory, cardiovascular, metabolic, immunological, hematological or hormonal&#xD;
             disorders.&#xD;
&#xD;
          -  Indication of liver disease, defined by serum levels of ALT (SGPT), AST (SGOT), or&#xD;
             alkaline phosphatase above 3x upper limit of normal (ULN) as determined during&#xD;
             screening.&#xD;
&#xD;
          -  Significant history of drug addiction (with the exception of nicotine dependence) or&#xD;
             abuse (including alcohol, as defined in DSM-V or in the opinion of the investigator)&#xD;
             within the last two years prior to informed consent, or a positive urine drug screen&#xD;
             for cocaine, opioid, phencyclidine (PCP), amphetamine or marijuana at screening.&#xD;
             Prescription medication yielding a positive drug screen are acceptable except for&#xD;
             tricyclic antidepressants (e.g. Amitriptyline, Amoxapine, Desipramine, (Norpramin)&#xD;
             Doxepin, Imipramine (Tofranil), Nortriptyline (Pamelor), Protriptyline (Vivactil),&#xD;
             Trimipramine (Surmontil)).&#xD;
&#xD;
          -  Clinically significant infection within the last 30 days prior screening (e.g.,&#xD;
             chronic persistent or acute infection, urinary tract infections (UTI)).&#xD;
&#xD;
          -  Treatment with immunosuppressive medications (e.g., systemic corticosteroids) within&#xD;
             the last 90 days (topical and nasal corticosteroids and inhaled corticosteroids for&#xD;
             asthma are permitted) or chemotherapeutic agents for malignancy within the last 3&#xD;
             years.&#xD;
&#xD;
          -  Myocardial infarction within the last year.&#xD;
&#xD;
          -  History of cancer within the last 3 years, with the exception of basal cell carcinoma&#xD;
             and non-metastatic squamous cell carcinoma of the skin and prostate cancer with&#xD;
             currently normal PSA.&#xD;
&#xD;
          -  Other clinically significant abnormality on physical, neurological, laboratory, or&#xD;
             electrocardiogram (ECG) examination (e.g., atrial fibrillation) that could compromise&#xD;
             the study or be detrimental to the participant.&#xD;
&#xD;
          -  Hemoglobin &lt; 11 g/dL.&#xD;
&#xD;
          -  Have any contraindication to MRI scanning, including cardiac pacemaker/defibrillator,&#xD;
             ferromagnetic metal implants (e.g., in skull and cardiac devices or severe&#xD;
             claustrophobia).&#xD;
&#xD;
          -  Smoking &gt; 1 pack of cigarettes per day (as assessed for the 30 days prior to&#xD;
             screening).&#xD;
&#xD;
          -  Alcohol use of more than 2 drinks per day.&#xD;
&#xD;
          -  Current use of over-the-counter (OTC) supplements or nutraceuticals unless they are on&#xD;
             stable dose for at least 3 months prior to screening and are documented in the eCRF.&#xD;
&#xD;
          -  Use of over the counter (OTC) or prescription medication for sleep on 2 or more&#xD;
             occasions per week.&#xD;
&#xD;
          -  Being treated with psychoactive medications on a stable dose for less than 3 month.&#xD;
&#xD;
          -  Any prior exposure to ANAVEX2-73.&#xD;
&#xD;
          -  Individuals enrolled in previous AD clinical trial involving an investigational drug&#xD;
             treatment less than 3 months ago (longer than 3 month ago allowed).&#xD;
&#xD;
          -  Any known hypersensitivity to any of the excipients contained in the study drug&#xD;
             formulation.&#xD;
&#xD;
          -  Any other criteria (such as a clinically significant screening blood test result),&#xD;
             which in the opinion of the Investigator causes the participant not to qualify for the&#xD;
             study.&#xD;
&#xD;
          -  Evidence of cerebrovascular dementia with a Hachinski score of 4 or more.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Central Coast Neurosciences Research</name>
      <address>
        <city>Central Coast</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hornsby (Northern Sydney Health)</name>
      <address>
        <city>Hornsby</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>KaRa MINDS</name>
      <address>
        <city>Macquarie Park</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent Hospital Sydney</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Sydney</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gold Coast Memory Disorders Clinic</name>
      <address>
        <city>Southport</city>
        <state>Quennsland</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Adelaide Hospital (RAH) and The Queen Elizabeth Hospital (TQEH)</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penninsula Therapeutic and Research Group</name>
      <address>
        <city>Frankston</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Geelong Private Medical Centre</name>
      <address>
        <city>Geelong</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Delmont Private Hospital</name>
      <address>
        <city>Glen Iris</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hammond Care</name>
      <address>
        <city>Malvern</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Alfred Psychiatry Research Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital (RMH)</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McCusker</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Healthy Brain Aging Labs Uni of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of British Columbia Hospital</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vancouver Island Health Authority</name>
      <address>
        <city>Victoria</city>
        <state>British Columbia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>True North Clinical Research</name>
      <address>
        <city>Kentville</city>
        <state>Nova Scotia</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkwood Institute</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bruyere Continuing Care</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kawartha Centre</name>
      <address>
        <city>Peterborough</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Crest Health Sciences</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Memory Program</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Toronto Western Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Ulm, Memory Clinic</name>
      <address>
        <city>Ulm</city>
        <state>Baden-Wuerttemberg</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bayreuth Clinic, Hohe Warte Hospital</name>
      <address>
        <city>Bayreuth</city>
        <state>Bavaria</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Technical University of Munich, School of Medicine</name>
      <address>
        <city>München</city>
        <state>Bavaria</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Institute of Mental Health</name>
      <address>
        <city>Mannheim</city>
        <state>Hessen</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Goettingen University Medicine, Clinic for Psychiatry and Psychotherapy</name>
      <address>
        <city>Göttingen</city>
        <state>Lower Saxony</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital, Bonn</name>
      <address>
        <city>Bonn</city>
        <state>North Rhine-Westphalia</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinic for Psychiatry and Psychotherapy</name>
      <address>
        <city>Mainz</city>
        <state>Rheinland-Pfalz</state>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charite University Medicine</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Research Center</name>
      <address>
        <city>Amsterdam</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Research Center</name>
      <address>
        <city>Den Bosch</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brain Research Center</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Teesside</city>
        <state>County Teesside</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Edinburgh</name>
      <address>
        <city>Edinburgh</city>
        <state>Scotland</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Memory Clinic</name>
      <address>
        <city>Glasgow</city>
        <state>Scotland</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognition Health</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Barnsley</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognition Health</name>
      <address>
        <city>Birmingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Blackpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Cannock</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Leeds</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Liverpool</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognition Health</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Imperial College</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>King's College</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MAC Clinical Research</name>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cognition Health</name>
      <address>
        <city>Plymouth</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southern Health NHS Foundation Trust</name>
      <address>
        <city>Southampton</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Germany</country>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>December 24, 2018</study_first_submitted>
  <study_first_submitted_qc>December 31, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">January 2, 2019</study_first_posted>
  <last_update_submitted>July 12, 2022</last_update_submitted>
  <last_update_submitted_qc>July 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03790709
org study id: ANAVEX2-73-AD-004
nct id: NCT03790709
lead sponsor: 
collaborator: 
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has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized 1:1:1 to two different ANAVEX2-73 doses or placebo
primary purpose: Treatment
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.
measure: ADAS-Cog (Alzheimer Disease Assessment Scale-Cognition)
time frame: 48 weeks
description: Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Alzheimer Disease Assessment Scale-Cognition (ADAS-Cog)
measure: ADCS-ADL (Activities of Daily Living)
time frame: 48 weeks
description: Reduction in decline of the ability to perform daily activities assessed from baseline over 48 weeks with ANAVEX2-73 compared to placebo using the Activities of Daily Living Scale (ADCS-ADL)
measure: CDR-SB (Clinical Dementia Rating Scale Sum of Boxes)
time frame: 48 weeks
description: Reduction in cognitive decline assessed from baseline over 48 weeks with ANAVEX2-73 compared with placebo using the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB)
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
time frame: 48 weeks
description: Assess the safety and tolerability of ANAVEX2-73 compared to placebo
measure: Number of participants with change of brain volume assessed by MRI
time frame: 48 weeks
description: To evaluate the effect of ANAVEX2-73 on structural and Arterial Spin Labeling (ASL) MRI scan assessments characteristic for AD pathophysiology compared to placebo over a 48-week treatment duration
measure: Blood assessment
time frame: 48 weeks
description: Blood assessment from baseline and compared to placebo at +48 weeks: Abeta40, Abeta42, T-tau, NFL, YKL-40, BACE1 concentration
measure: CSF assessment
time frame: 48 weeks
description: 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
measure: Number of participants with pre-specified genetic variants
time frame: 48 weeks
description: AD relevant pre-specified genetic variants will be assessed. Statistical testing of treatment differences within subgroups will be performed
measure: RSCAQ sleep score
time frame: Weeks 0, 4, 12, 24, 36, and 48
description: 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)
arm group label: High dose ANAVEX2-73
arm group type: Experimental
description: High dose active once daily orally
arm group label: Mid dose ANAVEX2-73
arm group type: Experimental
description: Mid dose active once daily orally
arm group label: Placebo oral capsule
arm group type: Placebo Comparator
description: Placebo dose once daily orally
intervention type: Drug
intervention name: High dose ANAVEX2-73
description: Oral capsule
arm group label: High dose ANAVEX2-73
intervention type: Drug
intervention name: Mid dose ANAVEX2-73
description: Oral capsule
arm group label: Mid dose ANAVEX2-73
intervention type: Drug
intervention name: Placebo oral capsule
description: Oral capsule
arm group label: Placebo oral capsule
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: No
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country: Australia
country: Canada
country: Germany
country: Netherlands
country: United Kingdom
responsible party type: Sponsor
mesh term: Alzheimer Disease