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

ANAVEX2-73-RS-003 is a Phase 2/3, Double-blind, Randomized, Placebo-controlled Safety and Efficacy Study in Pediatric Patients With RTT

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.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: ANAVEX2-73 oral liquid; Drug: Placebo oral liquid

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
• Enrollment (Actual): 92
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Walter Kaufmann, MD; Phone Number: +1(844)-689-3939; Email: rett@anavex.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2145
      • The Children's Hospital at Westmead
  • Queensland
    • Brisbane, Queensland, Australia, 4101
      • Queensland Children's Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3084
      • Austin Health
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Children's Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3V4
      • British Columbia Children's Hospital
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital LHSC
    • Toronto, Ontario, Canada, M5H 3W4
      • Holland Bloorview Kids Hospital
• United Kingdom
  • Edinburgh, United Kingdom, EH16 4TJ
    • Royal Hospital for Children
  • London, United Kingdom, SE1 7EH
    • Evelina London Children's Hospital
  • London, United Kingdom, SE5 8AF
    • King's College of London
  • Manchester, United Kingdom, M13 9WL
    • Manchester CGM, St Mary's Hospital
  • Nottingham, United Kingdom, NG7 2UH
    • Nottingham University Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ANAVEX2-73 Active; ANAVEX2-73 liquid oral solution	Drug: ANAVEX2-73 oral liquid; Liquid oral solution; Other Names: Blarcamesine
Placebo Comparator: ANAVEX2-73 Placebo; Placebo liquid oral solution	Drug: Placebo oral liquid; Liquid oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RSBQ	Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score	12 weeks
Incidents of Adverse Events	Change from baseline to End of Treatment (EOT)	12 weeks

Secondary Outcome Measures

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Anavex Life Sciences Corp.
• Collaborators: Anavex Australia Pty Ltd.; Anavex Germany GmbH

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): June 1, 2023
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: March 8, 2020
• First Submitted That Met QC Criteria: March 8, 2020
• First Posted (Actual): March 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 18, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: ANAVEX2-73-RS-003

Drug and device information, study documents

• 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