Study of ANAVEX2-73 in Patients With Rett Syndrome

Study Overview
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Brief Summary
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Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized, placebo-controlled study. 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients with RTT 18 years or older. A voluntary option will be offered for all patients who meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.

Detailed Description
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This Phase 2 safety, tolerability and efficacy study is designed as a double-blind, randomized, placebo-controlled study. This is a 7-week placebo-controlled study of ANAVEX2-73 oral solution for the treatment of patients with RTT 18 years or older. A voluntary option will be offered for all patients who meet the exposure criteria for ANAVEX2-73 to continue a 12-week open label extension.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled, Dose Titration Study of ANAVEX2-73 in Patients With Rett Syndrome

Conditions
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Rett Syndrome

Intervention / Treatment
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* Drug: ANAVEX2-73
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years, inclusive. Diagnosis of classic RTT, according to 2010 criteria (Neul et al., 2010), and a MECP2 mutation. Current pharmacological treatment regimen, including supplements, has been stable for at least 4 weeks. If on antiepileptic drugs (AEDs), 1-4 AEDs allowed. Treatment must be stable (drug, dose, interval of administration) for 30 days prior to enrollment. 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 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 of clinically evident stroke or clinically significant carotid or vertebrobasilar stenosis or plaque or other history of 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., atrial fibrillation) 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 on potent CYP 3A4 and CYP2C19 inhibitors and inducers. 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. Patients with hepatic and renal impairment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active arm<br>Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73) | Drug: ANAVEX2-73<br>* Liquid oral solution<br>|
| Placebo Comparator: Placebo arm<br>Week 0-7: Take 1 ml orally of the product daily (placebo) | Drug: Placebo<br>* Liquid oral solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Adverse Events | Incidence of Adverse Events | 7 weeks | 
| Maximum Plasma Concentration [Cmax] of ANAVEX2-73 | PK of ANAVEX2-73 and metabolite | 7 weeks | 
| Area Under the Curve [AUC] of ANAVEX2-73 | PK of ANAVEX2-73 and metabolite | 7 weeks | 
| Lipid panel | Significant laboratory findings | 7 weeks | 

Secondary 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 and a pre-specified subset of the RSBQ | 7 weeks | 
| CGI-I | Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score. Total score and a pre-specified subset of the CGI-I | 7 weeks |