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.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Rett Syndrome	Drug: ANAVEX2-73; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 31 participants
• 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
• Official Title: A Double-Blind, Randomized, Placebo-Controlled, Dose Titration Study of ANAVEX2-73 in Patients With Rett Syndrome
• Actual Study Start Date: February 28, 2019
• Actual Primary Completion Date: October 30, 2020
• Actual Study Completion Date: October 30, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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
2. 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

Other Outcome Measures:

1. Anxiety, Depression, and Mood Scale (ADAMS) [ Time Frame: 7 weeks ]
   Anxiety, Depression, and Mood Scale (ADAMS)
2. Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: 7 weeks ]
   Children's Sleep Habits Questionnaire (CSHQ)
3. Visual Analog Scale (VAS) [ Time Frame: 7 weeks ]
   Visual Analog Scale (VAS)
4. Seizure Frequency via seizure diary [ Time Frame: 7 weeks ]
   Seizure Frequency via seizure diary
5. Genetic variant SIGMAR1, COMT [ Time Frame: 7 weeks ]
   Pre-specified endpoint
6. Glutamate Plasma Concentration [ Time Frame: 7 weeks ]
   Biomarker
7. GABA Plasma Concentration [ Time Frame: 7 weeks ]
   Biomarker

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Alabama

UAB | The University of Alabama at Birmingham

Birmingham, Alabama, United States, 35294

United States, California

UC Davis University of California - Davis MIND Institute

Sacramento, California, United States, 95817

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Massachusetts

Boston Children's Hospital

Boston, Massachusetts, United States, 02115

United States, Missouri

Washington University in St. Louis | Saint Louis Children's Hospital

Saint Louis, Missouri, United States, 63110

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

United States, South Carolina

Greenwood Genetic Center

Greenwood, South Carolina, United States, 29646

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

Anavex Life Sciences Corp.

International Rett Syndrome Foundation Rettsyndrome.org

Investigators

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

More Information

• Responsible Party: Anavex Life Sciences Corp.
• ClinicalTrials.gov Identifier: NCT03758924
• Other Study ID Numbers: ANAVEX2-73-RS-001
• First Posted: November 29, 2018
• Last Update Posted: January 12, 2021
• Last Verified: January 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Additional relevant MeSH terms:

Rett Syndrome; Syndrome; Disease; Pathologic Processes; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System