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

• ClinicalTrials.gov Identifier: NCT03941444
• Recruitment Status: Completed
• First Posted: May 8, 2019
• Last Update Posted: January 27, 2022
• Sponsor: Anavex Life Sciences Corp.
• Information provided by (Responsible Party): Anavex Life Sciences Corp.

Tracking Information

• First Submitted Date: May 6, 2019
• First Posted Date: May 8, 2019
• Last Update Posted Date: January 27, 2022
• Actual Study Start Date: May 6, 2019
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 18, 2022)

• RSBQ [ Time Frame: 7 weeks ]
  Drug exposure-dependent response of the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score
• Incidence of Adverse Events [ Time Frame: 7 weeks ]
  Incidence of Adverse Events

Original Primary Outcome Measures (submitted: May 6, 2019)

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

Current Secondary Outcome Measures (submitted: January 18, 2022)

• CGI-I [ Time Frame: 7 weeks ]
  Drug exposure-dependent response of the Clinical Global Impression of Improvement Scale (CGI-I) score
• Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 7 weeks ]
  Drug exposure-dependent response of the Anxiety, Depression, and Mood Scale (ADAMS)
• Maximum Plasma Concentration [Cmax] of ANAVEX2-73 [ Time Frame: 7 weeks ]
  PK of ANAVEX2-73 and metabolite
• Area Under the Curve [AUC] of ANAVEX2-73 [ Time Frame: 7 weeks ]
  PK of ANAVEX2-73 and metabolite

Original Secondary Outcome Measures (submitted: May 6, 2019)

• RSBQ [ Time Frame: 7 weeks ]
  Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ)
• CGI-I [ Time Frame: 7 weeks ]
  Change from baseline to End of Treatment (EOT) in the Clinical Global Impression Improvement Scale (CGI-I) score

Current Other Pre-specified Outcome Measures (submitted: January 18, 2022)

• Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 7 weeks ]
  Children's Sleep Habits Questionnaire (CSHQ)
• Seizure Frequency via seizure diary [ Time Frame: 7 weeks ]
  Seizure Frequency via seizure diary
• Genetic variant SIGMAR1, COMT [ Time Frame: 7 weeks ]
  Genetic variant SIGMAR1, COMT
• Glutamate Plasma Concentration [ Time Frame: 7 weeks ]
  Glutamate Plasma Concentration
• GABA Plasma Concentration [ Time Frame: 7 weeks ]
  GABA Plasma Concentration
• Lipid panel [ Time Frame: 7 weeks ]
  Significant laboratory findings

Original Other Pre-specified Outcome Measures (submitted: May 6, 2019)

• Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 7 weeks ]
  Anxiety, Depression, and Mood Scale (ADAMS)
• Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 7 weeks ]
  Children's Sleep Habits Questionnaire (CSHQ)
• Seizure Frequency via seizure diary [ Time Frame: 7 weeks ]
  Seizure Frequency via seizure diary
• Genetic variant SIGMAR1, COMT [ Time Frame: 7 weeks ]
  Genetic variant SIGMAR1, COMT
• Glutamate Plasma Concentration [ Time Frame: 7 weeks ]
  Glutamate Plasma Concentration
• GABA Plasma Concentration [ Time Frame: 7 weeks ]
  GABA Plasma Concentration

Descriptive Information

• Brief Title: ANAVEX2-73 Study in Patients With Rett Syndrome
• Official Title: A Double-Blind, Randomized, Placebo-Controlled, Safety and Efficacy Study of ANAVEX2-73 in Patients With Rett Syndrome
• Brief Summary: 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.

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
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

36 participants: 3 PK open-label followed by 33 double-blind, randomized, placebo-controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

• Condition: Rett Syndrome

Intervention

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

Study Arms

• Experimental: Active arm
  ANAVEX2-73 liquid oral solution
  Intervention: Drug: ANAVEX2-73
• Placebo Comparator: Placebo arm
  Placebo liquid oral solution
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 15, 2022): 33
• Original Estimated Enrollment (submitted: May 6, 2019): 30
• Actual Study Completion Date: September 30, 2021
• Actual Primary Completion Date: September 30, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 45 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United Kingdom

Administrative Information

• NCT Number: NCT03941444
• Other Study ID Numbers: ANAVEX2-73-RS-002
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Anavex Life Sciences Corp.
• Original Responsible Party: Same as current
• Current Study Sponsor: Anavex Life Sciences Corp.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Anavex Life Sciences Corp.
• Verification Date: January 2022