<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/NCT03758924</url>
  </required_header>
  <id_info>
    <org_study_id>ANAVEX2-73-RS-001</org_study_id>
    <nct_id>NCT03758924</nct_id>
  </id_info>
  <brief_title>Study of ANAVEX2-73 in Patients With Rett Syndrome</brief_title>
  <official_title>A Double-Blind, Randomized, Placebo-Controlled, Dose Titration Study of ANAVEX2-73 in Patients With Rett Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Anavex Life Sciences Corp.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>International Rett Syndrome Foundation Rettsyndrome.org</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Anavex Life Sciences Corp.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized,&#xD;
      placebo-controlled study.&#xD;
&#xD;
      7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients&#xD;
      with RTT 18 years or older. A voluntary option will be offered for all patients who meet the&#xD;
      exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 2 safety, tolerability and efficacy study is designed as a double-blind,&#xD;
      randomized, placebo-controlled study.&#xD;
&#xD;
      This is a 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of&#xD;
      patients with RTT 18 years or older. A voluntary option will be offered for all patients who&#xD;
      meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 28, 2019</start_date>
  <completion_date type="Actual">October 30, 2020</completion_date>
  <primary_completion_date type="Actual">October 30, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double-Blind, Randomized, Placebo-Controlled</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Adverse Events</measure>
    <time_frame>7 weeks</time_frame>
    <description>Incidence of Adverse Events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration [Cmax] of ANAVEX2-73</measure>
    <time_frame>7 weeks</time_frame>
    <description>PK of ANAVEX2-73 and metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Curve [AUC] of ANAVEX2-73</measure>
    <time_frame>7 weeks</time_frame>
    <description>PK of ANAVEX2-73 and metabolite</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lipid panel</measure>
    <time_frame>7 weeks</time_frame>
    <description>Significant laboratory findings</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>RSBQ</measure>
    <time_frame>7 weeks</time_frame>
    <description>Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ). Total score and a pre-specified subset of the RSBQ</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CGI-I</measure>
    <time_frame>7 weeks</time_frame>
    <description>Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score. Total score and a pre-specified subset of the CGI-I</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Anxiety, Depression, and Mood Scale (ADAMS)</measure>
    <time_frame>7 weeks</time_frame>
    <description>Anxiety, Depression, and Mood Scale (ADAMS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Children's Sleep Habits Questionnaire (CSHQ)</measure>
    <time_frame>7 weeks</time_frame>
    <description>Children's Sleep Habits Questionnaire (CSHQ)</description>
  </other_outcome>
  <other_outcome>
    <measure>Visual Analog Scale (VAS)</measure>
    <time_frame>7 weeks</time_frame>
    <description>Visual Analog Scale (VAS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Seizure Frequency via seizure diary</measure>
    <time_frame>7 weeks</time_frame>
    <description>Seizure Frequency via seizure diary</description>
  </other_outcome>
  <other_outcome>
    <measure>Genetic variant SIGMAR1, COMT</measure>
    <time_frame>7 weeks</time_frame>
    <description>Pre-specified endpoint</description>
  </other_outcome>
  <other_outcome>
    <measure>Glutamate Plasma Concentration</measure>
    <time_frame>7 weeks</time_frame>
    <description>Biomarker</description>
  </other_outcome>
  <other_outcome>
    <measure>GABA Plasma Concentration</measure>
    <time_frame>7 weeks</time_frame>
    <description>Biomarker</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Rett Syndrome</condition>
  <arm_group>
    <arm_group_label>Active arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Week 0-7: Take 1 ml orally of the product daily (placebo)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ANAVEX2-73</intervention_name>
    <description>Liquid oral solution</description>
    <arm_group_label>Active arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Liquid oral solution</description>
    <arm_group_label>Placebo arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged ≥ 18 years, inclusive.&#xD;
&#xD;
          -  Diagnosis of classic RTT, according to 2010 criteria (Neul et al., 2010), and a MECP2&#xD;
             mutation.&#xD;
&#xD;
          -  Current pharmacological treatment regimen, including supplements, has been stable for&#xD;
             at least 4 weeks.&#xD;
&#xD;
          -  If on antiepileptic drugs (AEDs), 1-4 AEDs allowed. Treatment must be stable (drug,&#xD;
             dose, interval of administration) for 30 days prior to enrollment.&#xD;
&#xD;
          -  Ability to keep accurate seizure diaries or have caregiver who can keep accurate&#xD;
             seizure diaries.&#xD;
&#xD;
          -  Confirmation from the participant that, if of childbearing potential is not pregnant&#xD;
             through urine pregnancy testing. Female patients of childbearing potential and at risk&#xD;
             for pregnancy must agree to abstinence.&#xD;
&#xD;
          -  Prior to the conduct of study-specific procedures, the subject's parent/caregiver/LAR&#xD;
             must provide written informed consent. If applicable, the research team must attempt&#xD;
             to obtain consent from both parents.&#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.&#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 of clinically evident stroke or clinically significant carotid or&#xD;
             vertebrobasilar stenosis or plaque or other history of neurologic (e.g., head trauma&#xD;
             with loss of consciousness) or psychiatric condition that the Investigator deems may&#xD;
             interfere with interpretability of data.&#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;
          -  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;
          -  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;
          -  Any known hypersensitivity to any of the excipients contained in the study drug or&#xD;
             placebo formulation.&#xD;
&#xD;
          -  Other co-morbid or chronic illness beyond that known to be associated with RTT.&#xD;
&#xD;
          -  Subjects who plan to initiate or change pharmacologic or nonpharmacologic intervention&#xD;
             during the course of the study.&#xD;
&#xD;
          -  Subjects on potent CYP 3A4 and CYP2C19 inhibitors and inducers.&#xD;
&#xD;
          -  Subjects taking another investigational drug currently or within the last 30 days.&#xD;
&#xD;
          -  Any other criteria (such as a clinically significant screening blood test result),&#xD;
             which in the opinion of the Investigator could interfere with the study conduct or&#xD;
             outcome.&#xD;
&#xD;
          -  Patients with hepatic and renal impairment.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Walter Kaufmann, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University SOM</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UAB | The University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Davis University of California - Davis MIND Institute</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boston Children's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis | Saint Louis Children's Hospital</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenwood Genetic Center</name>
      <address>
        <city>Greenwood</city>
        <state>South Carolina</state>
        <zip>29646</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>January 11, 2021</last_update_submitted>
  <last_update_submitted_qc>January 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 12, 2021</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>Rett Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03758924
org study id: ANAVEX2-73-RS-001
nct id: NCT03758924
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized,
      placebo-controlled study.

      7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients
      with RTT 18 years or older. A voluntary option will be offered for all patients who meet the
      exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.
This Phase 2 safety, tolerability and efficacy study is designed as a double-blind,
      randomized, placebo-controlled study.

      This is a 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of
      patients with RTT 18 years or older. A voluntary option will be offered for all patients who
      meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: 31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Double-Blind, Randomized, Placebo-Controlled
measure: Incidence of Adverse Events
time frame: 7 weeks
description: Incidence of Adverse Events
measure: Maximum Plasma Concentration [Cmax] of ANAVEX2-73
time frame: 7 weeks
description: PK of ANAVEX2-73 and metabolite
measure: Area Under the Curve [AUC] of ANAVEX2-73
time frame: 7 weeks
description: PK of ANAVEX2-73 and metabolite
measure: Lipid panel
time frame: 7 weeks
description: Significant laboratory findings
measure: RSBQ
time frame: 7 weeks
description: Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ). Total score and a pre-specified subset of the RSBQ
measure: CGI-I
time frame: 7 weeks
description: Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score. Total score and a pre-specified subset of the CGI-I
measure: Anxiety, Depression, and Mood Scale (ADAMS)
time frame: 7 weeks
description: Anxiety, Depression, and Mood Scale (ADAMS)
measure: Children's Sleep Habits Questionnaire (CSHQ)
time frame: 7 weeks
description: Children's Sleep Habits Questionnaire (CSHQ)
measure: Visual Analog Scale (VAS)
time frame: 7 weeks
description: Visual Analog Scale (VAS)
measure: Seizure Frequency via seizure diary
time frame: 7 weeks
description: Seizure Frequency via seizure diary
measure: Genetic variant SIGMAR1, COMT
time frame: 7 weeks
description: Pre-specified endpoint
measure: Glutamate Plasma Concentration
time frame: 7 weeks
description: Biomarker
measure: GABA Plasma Concentration
time frame: 7 weeks
description: Biomarker
arm group label: Active arm
arm group type: Experimental
description: Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)
arm group label: Placebo arm
arm group type: Placebo Comparator
description: Week 0-7: Take 1 ml orally of the product daily (placebo)
intervention type: Drug
intervention name: ANAVEX2-73
description: Liquid oral solution
arm group label: Active arm
intervention type: Drug
intervention name: Placebo
description: Liquid oral solution
arm group label: Placebo arm
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Walter Kaufmann, MD
role: Principal Investigator
affiliation: Emory University SOM
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Rett Syndrome
mesh term: Syndrome
sharing ipd: No