Clinical trial NCT03758924: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rett Syndrome
Lead sponsor: Anavex Life Sciences Corp.
Sponsor class: INDUSTRY
Collaborators: name: International Rett Syndrome Foundation Rettsyndrome.org
First posted: 2018-11-29
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 31 participants: 6 PK open-label followed by 25 double-blind, randomized, placebo-controlled
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of Adverse Events
timeFrame: 7 weeks
measure: Maximum Plasma Concentration [Cmax] of ANAVEX2-73
timeFrame: 7 weeks
measure: Area Under the Curve [AUC] of ANAVEX2-73
timeFrame: 7 weeks
measure: Lipid panel
timeFrame: 7 weeks
Secondary outcomes:
measure: RSBQ
timeFrame: 7 weeks
measure: CGI-I
timeFrame: 7 weeks
Other outcomes:
measure: Anxiety, Depression, and Mood Scale (ADAMS)
timeFrame: 7 weeks
measure: Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: 7 weeks
measure: Visual Analog Scale (VAS)
timeFrame: 7 weeks
measure: Seizure Frequency via seizure diary
timeFrame: 7 weeks
measure: Genetic variant SIGMAR1, COMT
timeFrame: 7 weeks
measure: Glutamate Plasma Concentration
timeFrame: 7 weeks
measure: GABA Plasma Concentration
timeFrame: 7 weeks
Locations:
city: Birmingham
country: United States
facility: UAB | The University of Alabama at Birmingham
state: Alabama
city: Sacramento
country: United States
facility: UC Davis University of California - Davis MIND Institute
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University in St. Louis | Saint Louis Children's Hospital
state: Missouri
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Greenwood
country: United States
facility: Greenwood Genetic Center
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Emory University SOM
name: Walter Kaufmann, MD
role: PRINCIPAL_INVESTIGATOR
References: