Study of ANAVEX2-73 in Patients With Rett Syndrome

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

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.

Study Overview

• Status: Completed
• Conditions: Rett Syndrome
• Intervention / Treatment: Drug: ANAVEX2-73; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • UAB | The University of Alabama at Birmingham
  • California
    • Sacramento, California, United States, 95817
      • UC Davis University of California - Davis MIND Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St. Louis | Saint Louis Children's Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • South Carolina
    • Greenwood, South Carolina, United States, 29646
      • Greenwood Genetic Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Active arm; Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)	Drug: ANAVEX2-73; Liquid oral solution
PLACEBO_COMPARATOR: Placebo arm; Week 0-7: Take 1 ml orally of the product daily (placebo)	Drug: Placebo; Liquid oral solution

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Children's Sleep Habits Questionnaire (CSHQ)	Children's Sleep Habits Questionnaire (CSHQ)	7 weeks
Seizure Frequency via seizure diary	Seizure Frequency via seizure diary	7 weeks
Anxiety, Depression, and Mood Scale (ADAMS)	Anxiety, Depression, and Mood Scale (ADAMS)	7 weeks
Visual Analog Scale (VAS)	Visual Analog Scale (VAS)	7 weeks
Genetic variant SIGMAR1, COMT	Pre-specified endpoint	7 weeks
Glutamate Plasma Concentration	Biomarker	7 weeks
GABA Plasma Concentration	Biomarker	7 weeks

Collaborators and Investigators

• Sponsor: Anavex Life Sciences Corp.
• Collaborators: International Rett Syndrome Foundation Rettsyndrome.org
• Investigators: Principal Investigator: Walter Kaufmann, MD, Emory University SOM

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 28, 2019
• Primary Completion (ACTUAL): October 30, 2020
• Study Completion (ACTUAL): October 30, 2020

Study Registration Dates

• First Submitted: November 25, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (ACTUAL): November 29, 2018

Study Record Updates

• Last Update Posted (ACTUAL): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: ANAVEX2-73-RS-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No