Study of ANAVEX2-73 in Patients With Rett Syndrome

• ClinicalTrials.gov Identifier: NCT03758924
• Recruitment Status: Completed
• First Posted: November 29, 2018
• Last Update Posted: January 12, 2021
• Sponsor: Anavex Life Sciences Corp.
• Collaborator: International Rett Syndrome Foundation Rettsyndrome.org
• Information provided by (Responsible Party): Anavex Life Sciences Corp.

Tracking Information

• First Submitted Date: November 25, 2018
• First Posted Date: November 29, 2018
• Last Update Posted Date: January 12, 2021
• Actual Study Start Date: February 28, 2019
• Actual Primary Completion Date: October 30, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2018)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 28, 2018)

• RSBQ [ Time Frame: 7 weeks ]
  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
• CGI-I [ Time Frame: 7 weeks ]
  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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: November 28, 2018)

• 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)
• Visual Analog Scale (VAS) [ Time Frame: 7 weeks ]
  Visual Analog Scale (VAS)
• Seizure Frequency via seizure diary [ Time Frame: 7 weeks ]
  Seizure Frequency via seizure diary
• Genetic variant SIGMAR1, COMT [ Time Frame: 7 weeks ]
  Pre-specified endpoint
• Glutamate Plasma Concentration [ Time Frame: 7 weeks ]
  Biomarker
• GABA Plasma Concentration [ Time Frame: 7 weeks ]
  Biomarker

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

Brief 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.

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
• Study Phase: Phase 2

Study Design

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

31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Double-Blind, Randomized, Placebo-Controlled

Primary Purpose: Treatment

• Condition: Rett Syndrome

Intervention

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

Study Arms

• Experimental: Active arm
  Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)
  Intervention: Drug: ANAVEX2-73
• Placebo Comparator: Placebo arm
  Week 0-7: Take 1 ml orally of the product daily (placebo)
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 20, 2020): 31
• Original Estimated Enrollment (submitted: November 28, 2018): 15
• Actual Study Completion Date: October 30, 2020
• Actual Primary Completion Date: October 30, 2020 (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.
• 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.

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: United States

Administrative Information

• NCT Number: NCT03758924
• Other Study ID Numbers: ANAVEX2-73-RS-001
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• 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: International Rett Syndrome Foundation Rettsyndrome.org

Investigators

• Principal Investigator: Walter Kaufmann, MD; Emory University SOM

• PRS Account: Anavex Life Sciences Corp.
• Verification Date: January 2021