Study of ANAVEX2-73 in Patients With Rett Syndrome

Rett Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03758924
• Other study ID #: ANAVEX2-73-RS-001
• Status: Completed
• Phase: Phase 2
• Start date: February 28, 2019
• Est. completion date: October 30, 2020

Study information

• Verified date: January 2021
• Source: Anavex Life Sciences Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

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

Locations

Country	Name	City	State
United States	UAB | The University of Alabama at Birmingham	Birmingham	Alabama
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Greenwood Genetic Center	Greenwood	South Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	UC Davis University of California - Davis MIND Institute	Sacramento	California
United States	Washington University in St. Louis | Saint Louis Children's Hospital	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
Anavex Life Sciences Corp.	International Rett Syndrome Foundation Rettsyndrome.org

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Anxiety, Depression, and Mood Scale (ADAMS)	Anxiety, Depression, and Mood Scale (ADAMS)	7 weeks
Other	Children's Sleep Habits Questionnaire (CSHQ)	Children's Sleep Habits Questionnaire (CSHQ)	7 weeks
Other	Visual Analog Scale (VAS)	Visual Analog Scale (VAS)	7 weeks
Other	Seizure Frequency via seizure diary	Seizure Frequency via seizure diary	7 weeks
Other	Genetic variant SIGMAR1, COMT	Pre-specified endpoint	7 weeks
Other	Glutamate Plasma Concentration	Biomarker	7 weeks
Other	GABA Plasma Concentration	Biomarker	7 weeks
Primary	Incidence of Adverse Events	Incidence of Adverse Events	7 weeks
Primary	Maximum Plasma Concentration [Cmax] of ANAVEX2-73	PK of ANAVEX2-73 and metabolite	7 weeks
Primary	Area Under the Curve [AUC] of ANAVEX2-73	PK of ANAVEX2-73 and metabolite	7 weeks
Primary	Lipid panel	Significant laboratory findings	7 weeks
Secondary	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
Secondary	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