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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04304482
Recruitment Status : Recruiting
First Posted : March 11, 2020
Last Update Posted : May 9, 2022
Sponsor:
Collaborators:
Anavex Australia Pty Ltd.
Anavex Germany GmbH
Information provided by (Responsible Party):
Anavex Life Sciences Corp.

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.

Condition or disease Intervention/treatment Phase
Rett Syndrome Drug: ANAVEX2-73 oral liquid Drug: Placebo oral liquid Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : November 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Rett Syndrome

Arm Intervention/treatment
Experimental: ANAVEX2-73 Active
ANAVEX2-73 liquid oral solution
Drug: ANAVEX2-73 oral liquid
Liquid oral solution
Other Name: Blarcamesine

Placebo Comparator: ANAVEX2-73 Placebo
Placebo liquid oral solution
Drug: Placebo oral liquid
Liquid oral solution




Primary Outcome Measures :
  1. RSBQ [ Time Frame: 12 weeks ]
    Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score

  2. Incidents of Adverse Events [ Time Frame: 12 weeks ]
    Change from baseline to End of Treatment (EOT)


Secondary Outcome Measures :
  1. Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 12 weeks ]
    Anxiety, Depression, and Mood Scale (ADAMS)

  2. Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7) [ Time Frame: 12 weeks ]
    Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)

  3. Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 12 weeks ]
    Children's Sleep Habits Questionnaire (CSHQ)

  4. Seizure Frequency via seizure diary [ Time Frame: 12 weeks ]
    Seizure Frequency via seizure diary

  5. Incidence of Adverse Events [ Time Frame: 12 weeks ]
    Incidence of Adverse Events

  6. CGI-I [ Time Frame: 12 weeks ]
    Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score

  7. RSBQ Emotional Factor-Pediatric (subset of the RSBQ) [ Time Frame: 12 weeks ]
    RSBQ Emotional Factor-Pediatric (subset of the RSBQ)

  8. Rett Syndrome Caregiver Inventory Assessment (RTT CIA) [ Time Frame: 12 weeks ]
    Rett Syndrome Caregiver Inventory Assessment (RTT CIA)

  9. Child Health Questionnaire-Parent Form 50 (CHQ-PF50) [ Time Frame: 12 weeks ]
    Child Health Questionnaire-Parent Form 50 (CHQ-PF50)


Other Outcome Measures:
  1. Glutamate Plasma Concentration [ Time Frame: 12 weeks ]
    Glutamate Plasma Concentration

  2. GABA Plasma Concentration [ Time Frame: 12 weeks ]
    GABA Plasma Concentration

  3. Genetic variant SIGMAR1, COMT [ Time Frame: 12 weeks ]
    Genetic variant SIGMAR1, COMT

  4. Maximum Plasma Concentration [Cmax] [ Time Frame: 12 weeks ]
    Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  5. Maximum Plasma Concentration [Cmax] relationship with RSBQ [ Time Frame: 12 weeks ]
    Number of participants with positive Maximum Plasma Concentration [Cmax] relationship with RSBQ

  6. Other Amino Acid Plasma concentrations [ Time Frame: 12 weeks ]
    Other Amino Acid Plasma concentrations

  7. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04304482


Contacts
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Contact: Walter Kaufmann, MD +1(844)-689-3939 rett@anavex.com

Locations
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Australia, New South Wales
The Children's Hospital at Westmead Recruiting
Sydney, New South Wales, Australia, 2145
Contact: Carolyn Ellaway, MD         
Principal Investigator: Carolyn Ellaway, MD         
Australia, Queensland
Queensland Children's Hospital Recruiting
Brisbane, Queensland, Australia, 4101
Contact: Honey Heussler, MD         
Principal Investigator: Honey Heussler, MD         
Australia, Victoria
Austin Health Recruiting
Melbourne, Victoria, Australia, 3084
Contact: Ingrid Scheffer, MD         
Principal Investigator: Ingrid Scheffer, MD         
Canada, Alberta
Alberta Children's Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Julia Jacobs-Levan, MD         
Principal Investigator: Julia Jacobs-Levan, MD         
Canada, British Columbia
British Columbia Children's Hospital Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Anita Datta, MC         
Principal Investigator: Anita Datta, MD         
Canada, Ontario
Children's Hospital LHSC Not yet recruiting
London, Ontario, Canada, N6A 5W9
Contact: Janys Lim, MD         
Principal Investigator: Janys Lim, MD         
Holland Bloorview Kids Hospital Not yet recruiting
Toronto, Ontario, Canada, M5H 3W4
Contact: Evdokia Anagnostou, MD         
Principal Investigator: Evdokia Anagnostou, MD         
United Kingdom
Royal Hospital for Children Not yet recruiting
Edinburgh, United Kingdom, EH16 4TJ
Contact: Jay Shetty, MD         
Principal Investigator: Jay Shetty, MD         
Evelina London Children's Hospital Recruiting
London, United Kingdom, SE1 7EH
Contact: Daniel Lumsden, MD         
Principal Investigator: Daniel Lumsden, MD         
King's College of London Recruiting
London, United Kingdom, SE5 8AF
Contact: Santosh Paramala, MD         
Principal Investigator: Santosh Paramala, MD         
Manchester CGM, St Mary's Hospital Not yet recruiting
Manchester, United Kingdom, M13 9WL
Contact: Siddharth Banka, MD         
Principal Investigator: Siddharth Banka, MD         
Nottingham University Hospital NHS Trust Recruiting
Nottingham, United Kingdom, NG7 2UH
Contact: Katherine Martin, MD         
Principal Investigator: Katherine Martin, MD         
Sponsors and Collaborators
Anavex Life Sciences Corp.
Anavex Australia Pty Ltd.
Anavex Germany GmbH
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Anavex Life Sciences Corp.
ClinicalTrials.gov Identifier: NCT04304482    
Other Study ID Numbers: ANAVEX2-73-RS-003
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: May 9, 2022
Last Verified: May 2022

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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
Additional relevant MeSH terms:
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Rett Syndrome
Syndrome
Disease
Pathologic Processes
Mental Retardation, X-Linked
Intellectual Disability
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System