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History of Changes for Study: NCT04304482
ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome (EXCELLENCE)
Latest version (submitted September 27, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 8, 2020 None (earliest Version on record)
2 March 11, 2020 Arms and Interventions, Contacts/Locations and Study Status
3 April 11, 2020 Study Status
4 June 17, 2020 Study Status
5 June 25, 2020 Contacts/Locations and Study Status
6 September 1, 2020 Study Status
7 July 29, 2021 Study Status
8 September 27, 2021 Outcome Measures, Study Status, Eligibility, Study Description, Contacts/Locations, Study Design and Study Identification
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Changes (Side-by-Side) for Study: NCT04304482
July 29, 2021 (v7) -- September 27, 2021 (v8)

Changes in: Study Identification, Study Status, Study Description, Study Design, Outcome Measures, Eligibility and Contacts/Locations

Open or close this module Study Identification
Unique Protocol ID: ANAVEX2-73-RS-003 ANAVEX2-73-RS-003
Brief Title: ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome (EXCELLENCE)ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome (EXCELLENCE)
Official Title: A Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Study of ANAVEX2-73 in Patients With Rett Syndrome ANAVEX2-73-RS-003 is a Phase 2/3, Double-blind, Randomized, Placebo-controlled Safety and Efficacy Study in Pediatric Patients With RTT
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2021 September 2021
Overall Status: RecruitingRecruiting
Study Start: July 1, 2020 July 1, 2020
Primary Completion: November 2021 [Anticipated] May 1, 2022 [Anticipated]
Study Completion: November 2021 [Anticipated] June 1, 2022 [Anticipated]
First Submitted: March 8, 2020 March 8, 2020
First Submitted that
Met QC Criteria:
March 8, 2020 March 8, 2020
First Posted: March 11, 2020 [Actual] March 11, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
July 29, 2021 September 27, 2021
Last Update Posted: August 2, 2021 [Actual] September 28, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Anavex Life Sciences Corp. Anavex Life Sciences Corp.
Responsible Party: Sponsor Sponsor
Collaborators: Anavex Australia Pty Ltd.
Anavex Germany GmbH
Anavex Australia Pty Ltd.
Anavex Germany GmbH
Open or close this module Oversight
U.S. FDA-regulated Drug: YesYes
U.S. FDA-regulated Device: NoNo
Data Monitoring: Yes Yes
Open or close this module Study Description
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 5-18 years of age with RTT using endpoints including multiple clinical and exploratory molecular and biochemical measures. 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 5-18 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.

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.

Open or close this module Conditions
Conditions: Rett Syndrome Rett Syndrome
Keywords:
Open or close this module Study Design
Study Type: InterventionalInterventional
Primary Purpose: TreatmentTreatment
Study Phase: Phase 2/Phase 3Phase 2/Phase 3
Interventional Study Model: Parallel Assignment Parallel Assignment
Number of Arms: 22
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: RandomizedRandomized
Enrollment: 69 [Anticipated] 84 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module Outcome Measures
Primary Outcome Measures:
1. RSBQ
[ Time Frame: 12 weeks ]

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

Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score
2. CGI-I
[ Time Frame: 12 weeks ]

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

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

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

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

Genetic variant SIGMAR1, COMT
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
Open or close this module Eligibility
Minimum Age: 5 Years 5 Years
Maximum Age: 18 Years 17 Years
Sex: Female Female
Gender Based:
Accepts Healthy Volunteers: NoNo
Criteria:

Inclusion Criteria:

  • Aged ≥ 5 years to <18.
  • 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.
  • Ability to keep accurate seizure diaries or have caregiver who can keep accurate seizure diaries.
  • Confirmation from the participant that, if of childbearing potential is not pregnant through urine (or serum) pregnancy testing. Female patients of childbearing potential and at risk for pregnancy must agree to abstinence.
  • 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.
  • Subjects on potent CYP 3A4 and CYP2C19 inhibitors and inducers (e.g., oxcarbazepine).
  • Patients with hepatic and renal impairment.

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.
Open or close this module Contacts/Locations
Central Contact Person: Walter Kaufmann, MD
Telephone: +1(844)-689-3939
Email: rett@anavex.com
Walter Kaufmann, MD
Telephone: +1(844)-689-3939
Email: rett@anavex.com
Locations: Australia, New South WalesAustralia, New South Wales
The Children's Hospital at Westmead
[Recruiting]
Sydney, New South Wales, Australia, 2145
Contact:Contact: Carolyn Ellaway, MD
Contact:Principal Investigator: Carolyn Ellaway, MD
The Children's Hospital at Westmead
[Recruiting]
Sydney, New South Wales, Australia, 2145
Contact:Contact: Carolyn Ellaway, MD
Contact:Principal Investigator: Carolyn Ellaway, MD
Australia, QueenslandAustralia, Queensland
Queensland Children's Hospital
[Recruiting]
Brisbane, Queensland, Australia, 4101
Contact:Contact: Honey Heussler, MD
Contact:Principal Investigator: Honey Heussler, MD
Queensland Children's Hospital
[Recruiting]
Brisbane, Queensland, Australia, 4101
Contact:Contact: Honey Heussler, MD
Contact:Principal Investigator: Honey Heussler, MD
Australia, Victoria
Austin Health
[Recruiting]
Melbourne, Victoria, Australia, 3084
Contact:Contact: Ingrid Scheffer, MD
Contact:Principal Investigator: Ingrid Scheffer, MD
Canada, British Columbia
British Columbia Children's Hospital
[Recruiting]
Vancouver, British Columbia, Canada, V6H 3V4
Contact:Contact: Anita Datta, MC
Contact:Principal Investigator: Anita Datta, MD
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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