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Study of ANAVEX2-73 in Patients With Rett Syndrome

Primary Purpose

Rett Syndrome

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ANAVEX2-73
Placebo
Sponsored by
Anavex Life Sciences Corp.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rett Syndrome

Eligibility Criteria

18 Years - 45 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • UAB | The University of Alabama at Birmingham
  • UC Davis University of California - Davis MIND Institute
  • Rush University Medical Center
  • Boston Children's Hospital
  • Washington University in St. Louis | Saint Louis Children's Hospital
  • Cincinnati Children's Hospital Medical Center
  • Greenwood Genetic Center
  • Baylor College of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active arm

Placebo arm

Arm Description

Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)

Week 0-7: Take 1 ml orally of the product daily (placebo)

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
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

Full Information

First Posted
November 25, 2018
Last Updated
January 11, 2021
Sponsor
Anavex Life Sciences Corp.
Collaborators
International Rett Syndrome Foundation Rettsyndrome.org
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1. Study Identification

Unique Protocol Identification Number
NCT03758924
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2021
Overall Recruitment Status
Completed
Study Start Date
February 28, 2019 (Actual)
Primary Completion Date
October 30, 2020 (Actual)
Study Completion Date
October 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Anavex Life Sciences Corp.
Collaborators
International Rett Syndrome Foundation Rettsyndrome.org

4. Oversight

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

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rett Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-Blind, Randomized, Placebo-Controlled
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active arm
Arm Type
Experimental
Arm Description
Week 0-7: Take 1 ml orally of the product daily (solution of ANAVEX2-73)
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
Week 0-7: Take 1 ml orally of the product daily (placebo)
Intervention Type
Drug
Intervention Name(s)
ANAVEX2-73
Intervention Description
Liquid oral solution
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Liquid oral solution
Primary Outcome Measure Information:
Title
Incidence of Adverse Events
Description
Incidence of Adverse Events
Time Frame
7 weeks
Title
Maximum Plasma Concentration [Cmax] of ANAVEX2-73
Description
PK of ANAVEX2-73 and metabolite
Time Frame
7 weeks
Title
Area Under the Curve [AUC] of ANAVEX2-73
Description
PK of ANAVEX2-73 and metabolite
Time Frame
7 weeks
Title
Lipid panel
Description
Significant laboratory findings
Time Frame
7 weeks
Secondary Outcome Measure Information:
Title
RSBQ
Description
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
Time Frame
7 weeks
Title
CGI-I
Description
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
Time Frame
7 weeks
Other Pre-specified Outcome Measures:
Title
Anxiety, Depression, and Mood Scale (ADAMS)
Description
Anxiety, Depression, and Mood Scale (ADAMS)
Time Frame
7 weeks
Title
Children's Sleep Habits Questionnaire (CSHQ)
Description
Children's Sleep Habits Questionnaire (CSHQ)
Time Frame
7 weeks
Title
Visual Analog Scale (VAS)
Description
Visual Analog Scale (VAS)
Time Frame
7 weeks
Title
Seizure Frequency via seizure diary
Description
Seizure Frequency via seizure diary
Time Frame
7 weeks
Title
Genetic variant SIGMAR1, COMT
Description
Pre-specified endpoint
Time Frame
7 weeks
Title
Glutamate Plasma Concentration
Description
Biomarker
Time Frame
7 weeks
Title
GABA Plasma Concentration
Description
Biomarker
Time Frame
7 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Walter Kaufmann, MD
Organizational Affiliation
Emory University SOM
Official's Role
Principal Investigator
Facility Information:
Facility Name
UAB | The University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UC Davis University of California - Davis MIND Institute
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Washington University in St. Louis | Saint Louis Children's Hospital
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Greenwood Genetic Center
City
Greenwood
State/Province
South Carolina
ZIP/Postal Code
29646
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Study of ANAVEX2-73 in Patients With Rett Syndrome

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