ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome

Rett Syndrome Clinical Trial

— EXCELLENCE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04304482
• Other study ID #: ANAVEX2-73-RS-003
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 1, 2020
• Est. completion date: June 30, 2023

Study information

• Verified date: August 2023
• Source: Anavex Life Sciences Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: June 30, 2023
• Est. primary completion date: June 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 5 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
Australia	Queensland Children's Hospital	Brisbane	Queensland
Australia	Austin Health	Melbourne	Victoria
Australia	The Children's Hospital at Westmead	Sydney	New South Wales
Canada	Alberta Children's Hospital	Calgary	Alberta
Canada	Children's Hospital LHSC	London	Ontario
Canada	Holland Bloorview Kids Hospital	Toronto	Ontario
Canada	British Columbia Children's Hospital	Vancouver	British Columbia
United Kingdom	Royal Hospital for Children	Edinburgh
United Kingdom	Evelina London Children's Hospital	London
United Kingdom	King's College of London	London
United Kingdom	Manchester CGM, St Mary's Hospital	Manchester
United Kingdom	Nottingham University Hospital NHS Trust	Nottingham

Sponsors (3)

Lead Sponsor	Collaborator
Anavex Life Sciences Corp.	Anavex Australia Pty Ltd., Anavex Germany GmbH

Countries where clinical trial is conducted

Australia,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Glutamate Plasma Concentration	Glutamate Plasma Concentration	12 weeks
Other	GABA Plasma Concentration	GABA Plasma Concentration	12 weeks
Other	Genetic variant SIGMAR1, COMT	Genetic variant SIGMAR1, COMT	12 weeks
Other	Maximum Plasma Concentration [Cmax]	Number of participants with treatment-related adverse events as assessed by CTCAE v5.0	12 weeks
Other	Maximum Plasma Concentration [Cmax] relationship with RSBQ	Number of participants with positive Maximum Plasma Concentration [Cmax] relationship with RSBQ	12 weeks
Other	Other Amino Acid Plasma concentrations	Other Amino Acid Plasma concentrations	12 weeks
Other	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
Primary	RSBQ	Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score	12 weeks
Primary	Incidents of Adverse Events	Change from baseline to End of Treatment (EOT)	12 weeks
Secondary	CGI-I	Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score	12 weeks
Secondary	Anxiety, Depression, and Mood Scale (ADAMS)	Anxiety, Depression, and Mood Scale (ADAMS)	12 weeks
Secondary	Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)	Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)	12 weeks
Secondary	Children's Sleep Habits Questionnaire (CSHQ)	Children's Sleep Habits Questionnaire (CSHQ)	12 weeks
Secondary	Seizure Frequency via seizure diary	Seizure Frequency via seizure diary	12 weeks
Secondary	Incidence of Adverse Events	Incidence of Adverse Events	12 weeks
Secondary	RSBQ Emotional Factor-Pediatric (subset of the RSBQ)	RSBQ Emotional Factor-Pediatric (subset of the RSBQ)	12 weeks
Secondary	Rett Syndrome Caregiver Inventory Assessment (RTT CIA)	Rett Syndrome Caregiver Inventory Assessment (RTT CIA)	12 weeks
Secondary	Child Health Questionnaire-Parent Form 50 (CHQ-PF50)	Child Health Questionnaire-Parent Form 50 (CHQ-PF50)	12 weeks