ANAVEX2-73 Study in Patients With Rett Syndrome (AVATAR)

A Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Study of ANAVEX2-73 in Patients With Rett Syndrome

ANAVEX2-73-RS-002 is a Phase 3, double-blind, randomized, placebo-controlled dose escalation safety, tolerability and efficacy study in patients 18 years and older with RTT using endpoints including multiple clinical and exploratory molecular and biochemical measures.

Study Overview

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

Detailed Description

This Phase 3 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 to continue a 48-week open label extension.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Greenwich, New South Wales, Australia, 2065
      • HammondCare
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordiae Ltd
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • The Alfred Hospital
    • Melbourne, Victoria, Australia, 3050
      • Royal Melbourne Hospital (RMH)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • The Keogh Institute for Medical Research
• United Kingdom
  • UK
    • London, UK, United Kingdom, SE5 8AF
      • King's College of London
    • Manchester, UK, United Kingdom, M13 9WL
      • Manchester CGM, St. Mary's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 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.
• 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/legally authorized representative (LAR) will not electively initiate new or modify ongoing interventions for the duration of the study. 'Study duration' is defined as lasting from the screening visit until the treatment is terminated. For participants in the 16-21 years range, typical school vacations are not considered modifications of stable programming.
• 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

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 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.
• Subjects on potent CYP3A4 and CYP2C19 inhibitors and inducers.
• Patients with hepatic and renal impairment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active arm; ANAVEX2-73 liquid oral solution	Drug: ANAVEX2-73; Liquid oral solution
Placebo Comparator: Placebo arm; Placebo liquid oral solution	Drug: Placebo; Liquid oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RSBQ	Drug exposure-dependent response of the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score	7 weeks
Incidence of Adverse Events	Incidence of Adverse Events	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CGI-I	Drug exposure-dependent response of the Clinical Global Impression of Improvement Scale (CGI-I) score	7 weeks
Anxiety, Depression, and Mood Scale (ADAMS)	Drug exposure-dependent response of the Anxiety, Depression, and Mood Scale (ADAMS)	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

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
Genetic variant SIGMAR1, COMT	Genetic variant SIGMAR1, COMT	7 weeks
Glutamate Plasma Concentration	Glutamate Plasma Concentration	7 weeks
GABA Plasma Concentration	GABA Plasma Concentration	7 weeks
Lipid panel	Significant laboratory findings	7 weeks

Collaborators and Investigators

• Sponsor: Anavex Life Sciences Corp.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): September 30, 2021

Study Registration Dates

• First Submitted: May 6, 2019
• First Submitted That Met QC Criteria: May 6, 2019
• First Posted (Actual): May 8, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2022
• Last Update Submitted That Met QC Criteria: January 18, 2022
• Last Verified: January 1, 2022

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-002

Drug and device information, study documents

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