Clinical trial NCT03941444: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Rett Syndrome
Lead sponsor: Anavex Life Sciences Corp.
Sponsor class: INDUSTRY
First posted: 2019-05-08
Enrollment: 33
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: 36 participants: 3 PK open-label followed by 33 double-blind, randomized, placebo-controlled
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: RSBQ
timeFrame: 7 weeks
measure: Incidence of Adverse Events
timeFrame: 7 weeks
Secondary outcomes:
measure: CGI-I
timeFrame: 7 weeks
measure: Anxiety, Depression, and Mood Scale (ADAMS)
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
Other outcomes:
measure: Children's Sleep Habits Questionnaire (CSHQ)
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
measure: Lipid panel
timeFrame: 7 weeks
Locations:
city: Greenwich
country: Australia
facility: HammondCare
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordiae Ltd
state: Queensland
city: Melbourne
country: Australia
facility: Royal Melbourne Hospital (RMH)
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: The Keogh Institute for Medical Research
state: Western Australia
city: London
country: United Kingdom
facility: King's College of London
state: UK
city: Manchester
country: United Kingdom
facility: Manchester CGM, St. Mary's Hospital
state: UK
Study officials:
References: