Clinical trial NCT04304482: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Rett Syndrome
Lead sponsor: Anavex Life Sciences Corp.
Sponsor class: INDUSTRY
Collaborators: name: Anavex Australia Pty Ltd.
name: Anavex Germany GmbH
First posted: 2020-03-11
Enrollment: 92
Sex: FEMALE
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: RSBQ
timeFrame: 12 weeks
measure: Incidents of Adverse Events
timeFrame: 12 weeks
Secondary outcomes:
measure: CGI-I
timeFrame: 12 weeks
measure: Anxiety, Depression, and Mood Scale (ADAMS)
timeFrame: 12 weeks
measure: Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)
timeFrame: 12 weeks
measure: Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: 12 weeks
measure: Seizure Frequency via seizure diary
timeFrame: 12 weeks
measure: Incidence of Adverse Events
timeFrame: 12 weeks
measure: RSBQ Emotional Factor-Pediatric (subset of the RSBQ)
timeFrame: 12 weeks
measure: Rett Syndrome Caregiver Inventory Assessment (RTT CIA)
timeFrame: 12 weeks
measure: Child Health Questionnaire-Parent Form 50 (CHQ-PF50)
timeFrame: 12 weeks
Other outcomes:
measure: Glutamate Plasma Concentration
timeFrame: 12 weeks
measure: GABA Plasma Concentration
timeFrame: 12 weeks
measure: Genetic variant SIGMAR1, COMT
timeFrame: 12 weeks
measure: Maximum Plasma Concentration [Cmax]
timeFrame: 12 weeks
measure: Maximum Plasma Concentration [Cmax] relationship with RSBQ
timeFrame: 12 weeks
measure: Other Amino Acid Plasma concentrations
timeFrame: 12 weeks
measure: Measure of gene DNA variants and gene RNA expressions
timeFrame: 12 weeks
Locations:
city: Sydney
country: Australia
facility: The Children's Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Children's Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Austin Health
state: Victoria
city: Calgary
country: Canada
facility: Alberta Children's Hospital
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Children's Hospital
state: British Columbia
city: London
country: Canada
facility: Children's Hospital LHSC
state: Ontario
city: Toronto
country: Canada
facility: Holland Bloorview Kids Hospital
state: Ontario
city: Edinburgh
country: United Kingdom
facility: Royal Hospital for Children
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
city: London
country: United Kingdom
facility: King's College of London
city: Manchester
country: United Kingdom
facility: Manchester CGM, St Mary's Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospital NHS Trust
Study officials:
References:
citation: 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.