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ANAVEX2-73 Study in Patients With Rett Syndrome

Phase 3
Completed
Conditions
Rett Syndrome
Interventions
Drug: ANAVEX2-73
Drug: Placebo
Registration Number
NCT03941444
Lead Sponsor
Anavex Life Sciences Corp.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
33
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
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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.
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Active armANAVEX2-73ANAVEX2-73 liquid oral solution
Placebo armPlaceboPlacebo liquid oral solution
Primary Outcome Measures
NameTimeMethod
Incidence of Adverse Events7 weeks

Incidence of Adverse Events

RSBQ7 weeks

Drug exposure-dependent response of the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score

Secondary Outcome Measures
NameTimeMethod
Maximum Plasma Concentration [Cmax] of ANAVEX2-737 weeks

PK of ANAVEX2-73 and metabolite

Anxiety, Depression, and Mood Scale (ADAMS)7 weeks

Drug exposure-dependent response of the Anxiety, Depression, and Mood Scale (ADAMS)

CGI-I7 weeks

Drug exposure-dependent response of the Clinical Global Impression of Improvement Scale (CGI-I) score

Area Under the Curve [AUC] of ANAVEX2-737 weeks

PK of ANAVEX2-73 and metabolite

Trial Locations

Locations (7)

Manchester CGM, St. Mary's Hospital

🇬🇧

Manchester, UK, United Kingdom

HammondCare

🇦🇺

Greenwich, New South Wales, Australia

King's College of London

🇬🇧

London, UK, United Kingdom

Mater Misericordiae Ltd

🇦🇺

South Brisbane, Queensland, Australia

The Keogh Institute for Medical Research

🇦🇺

Nedlands, Western Australia, Australia

Royal Melbourne Hospital (RMH)

🇦🇺

Melbourne, Victoria, Australia

The Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

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