ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome (EXCELLENCE)

• ClinicalTrials.gov Identifier: NCT04304482
• Recruitment Status: Completed
• First Posted: March 11, 2020
• Last Update Posted: August 21, 2023
• Sponsor: Anavex Life Sciences Corp.
• Collaborators: Anavex Australia Pty Ltd.; Anavex Germany GmbH
• Information provided by (Responsible Party): Anavex Life Sciences Corp.

Tracking Information

• First Submitted Date: March 8, 2020
• First Posted Date: March 11, 2020
• Last Update Posted Date: August 21, 2023
• Actual Study Start Date: July 1, 2020
• Actual Primary Completion Date: June 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 27, 2021)

• RSBQ [ Time Frame: 12 weeks ]
  Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score
• Incidents of Adverse Events [ Time Frame: 12 weeks ]
  Change from baseline to End of Treatment (EOT)

Original Primary Outcome Measures (submitted: March 8, 2020)

• RSBQ [ Time Frame: 12 weeks ]
  Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ)
• CGI-I [ Time Frame: 12 weeks ]
  Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score

Current Secondary Outcome Measures (submitted: January 31, 2023)

• CGI-I [ Time Frame: 12 weeks ]
  Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score
• Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 12 weeks ]
  Anxiety, Depression, and Mood Scale (ADAMS)
• Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7) [ Time Frame: 12 weeks ]
  Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)
• Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 12 weeks ]
  Children's Sleep Habits Questionnaire (CSHQ)
• Seizure Frequency via seizure diary [ Time Frame: 12 weeks ]
  Seizure Frequency via seizure diary
• Incidence of Adverse Events [ Time Frame: 12 weeks ]
  Incidence of Adverse Events
• RSBQ Emotional Factor-Pediatric (subset of the RSBQ) [ Time Frame: 12 weeks ]
  RSBQ Emotional Factor-Pediatric (subset of the RSBQ)
• Rett Syndrome Caregiver Inventory Assessment (RTT CIA) [ Time Frame: 12 weeks ]
  Rett Syndrome Caregiver Inventory Assessment (RTT CIA)
• Child Health Questionnaire-Parent Form 50 (CHQ-PF50) [ Time Frame: 12 weeks ]
  Child Health Questionnaire-Parent Form 50 (CHQ-PF50)

Original Secondary Outcome Measures (submitted: March 8, 2020)

• Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 12 weeks ]
  Anxiety, Depression, and Mood Scale (ADAMS)
• Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7) [ Time Frame: 12 weeks ]
  Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)
• Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 12 weeks ]
  Children's Sleep Habits Questionnaire (CSHQ)
• Seizure Frequency via seizure diary [ Time Frame: 12 weeks ]
  Seizure Frequency via seizure diary
• Incidence of Adverse Events [ Time Frame: 12 weeks ]
  Incidence of Adverse Events

Current Other Pre-specified Outcome Measures (submitted: September 27, 2021)

• Glutamate Plasma Concentration [ Time Frame: 12 weeks ]
  Glutamate Plasma Concentration
• GABA Plasma Concentration [ Time Frame: 12 weeks ]
  GABA Plasma Concentration
• Genetic variant SIGMAR1, COMT [ Time Frame: 12 weeks ]
  Genetic variant SIGMAR1, COMT
• Maximum Plasma Concentration [Cmax] [ Time Frame: 12 weeks ]
  Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
• Maximum Plasma Concentration [Cmax] relationship with RSBQ [ Time Frame: 12 weeks ]
  Number of participants with positive Maximum Plasma Concentration [Cmax] relationship with RSBQ
• Other Amino Acid Plasma concentrations [ Time Frame: 12 weeks ]
  Other Amino Acid Plasma concentrations
• Measure of gene DNA variants and gene RNA expressions [ Time Frame: 12 weeks ]
  Number of participants with active dose compared gene DNA variants and gene RNA expressions

Original Other Pre-specified Outcome Measures (submitted: March 8, 2020)

• Glutamate Plasma Concentration [ Time Frame: 12 weeks ]
  Glutamate Plasma Concentration
• GABA Plasma Concentration [ Time Frame: 12 weeks ]
  GABA Plasma Concentration
• Genetic variant SIGMAR1, COMT [ Time Frame: 12 weeks ]
  Genetic variant SIGMAR1, COMT

Descriptive Information

• Brief Title: ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome
• Official Title: ANAVEX2-73-RS-003 is a Phase 2/3, Double-blind, Randomized, Placebo-controlled Safety and Efficacy Study in Pediatric Patients With RTT
• Brief Summary: ANAVEX2-73-RS-003 is a Phase 2/3, double-blind, randomized, placebo-controlled dose escalation safety, tolerability and efficacy study in patients 5-17 years of age with RTT using endpoints including multiple clinical and exploratory molecular and biochemical measures.

Detailed Description

This Phase 2/3 efficacy study is designed as a double-blind, randomized, placebo-controlled study.

This is a 12-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients with RTT 5-17 years of age. A voluntary option will be offered for all patients who meet the exposure criteria for ANAVEX2-73 to continue a 48-week open label extension.

• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Rett Syndrome

Intervention

• Drug: ANAVEX2-73 oral liquid
  Liquid oral solution
  Other Name: Blarcamesine
• Drug: Placebo oral liquid
  Liquid oral solution

Study Arms

• Experimental: ANAVEX2-73 Active
  ANAVEX2-73 liquid oral solution
  Intervention: Drug: ANAVEX2-73 oral liquid
• Placebo Comparator: ANAVEX2-73 Placebo
  Placebo liquid oral solution
  Intervention: Drug: Placebo oral liquid

• Publications *: Heussler HS. Emerging Therapies and challenges for individuals with Angelman syndrome. Curr Opin Psychiatry. 2021 Mar 1;34(2):123-128. doi: 10.1097/YCO.0000000000000674. Erratum In: Curr Opin Psychiatry. 2021 Sep 1;34(5):514.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 7, 2023): 92
• Original Estimated Enrollment (submitted: March 8, 2020): 69
• Actual Study Completion Date: June 30, 2023
• Actual Primary Completion Date: June 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Aged ≥ 5 years to 17 (inclusive).
• Diagnosis of classic RTT, according to 2010 criteria, and a MECP2 mutation.
• Post-regression stage, defined as ≥ 6 months since last loss of spoken language or motor (fine or gross) skills.
• Clinical Global Impression - Severity (CGI-S) score of 4 or greater at Screening.
• Current pharmacological treatment regimen, including supplements, has been stable for at least 4 weeks.
• If on AEDs, 1-4 AEDs allowed. Treatment must be stable (drug, dose, interval of administration) for 30 days prior to enrollment.
• If the subject is already receiving stable non-pharmacologic educational, behavioral, and/or dietary interventions, participation in these programs must have been continuous during the 90 days prior to the screening visit and subjects or their parent/caregiver/LAR will not electively initiate new or modify ongoing interventions for the duration of the study.
• The subject's caregiver/LAR is English-speaking and has sufficient language skills to complete the caregiver assessments and has the ability to keep accurate seizure diaries.
• If participant is a woman of childbearing potential (WOCBP#), a negative urine or serum pregnancy test is required to confirm she is not pregnant.
• Prior to the conduct of study-specific procedures, the subject's parent/caregiver/LAR must provide written informed consent. If applicable, the research team must attempt to obtain consent from both parents.

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.
• 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 neurologic (e.g., head trauma with loss of consciousness) or psychiatric condition that the Investigator deems may interfere with interpretability of data.
• 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.
• 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.
• Other clinically significant abnormality on physical, neurological, laboratory, or electrocardiogram (ECG) examination (e.g., long QT) that could compromise the study or be detrimental to the participant.
• Any known hypersensitivity to any of the excipients contained in the study drug or placebo formulation.
• Other co-morbid or chronic illness beyond that known to be associated with RTT.
• Subjects who plan to initiate or change pharmacologic or nonpharmacologic intervention during the course of the study.
• Subjects taking another investigational drug currently or within the last 30 days.
• Any other criteria (such as a clinically significant screening blood test result), which in the opinion of the Investigator could interfere with the study conduct or outcome.
• Treatment with strong inhibitors or inducers of CYP3A4 or CYP2C19 is not stable (drug, dose) for 30 days prior to screening. Although these medications are not excluded, caution is advised when enrolling participants on potent CYP3A4 or CYP2C19 inducers or inhibitors (see respective section).
• Patients with hepatic and renal impairment.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 5 Years to 17 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, United Kingdom

Administrative Information

• NCT Number: NCT04304482
• Other Study ID Numbers: ANAVEX2-73-RS-003
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Anavex Life Sciences Corp.
• Original Responsible Party: Same as current
• Current Study Sponsor: Anavex Life Sciences Corp.
• Original Study Sponsor: Same as current

Collaborators

• Anavex Australia Pty Ltd.
• Anavex Germany GmbH

• Investigators: Not Provided
• PRS Account: Anavex Life Sciences Corp.
• Verification Date: August 2023