ANAVEX2-73 Study in Patients With Rett Syndrome

NCT03941444 | Completed Phase 3 DMC

• 1 other identifier: ANAVEX2-73-RS-002
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 7

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.

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (2)

• RSBQ

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

  7 weeks

• Incidence of Adverse Events

  Incidence of Adverse Events

  7 weeks

Secondary Outcomes (4)

• CGI-I

  7 weeks

• Anxiety, Depression, and Mood Scale (ADAMS)

  7 weeks

• Maximum Plasma Concentration [Cmax] of ANAVEX2-73

  7 weeks

• Area Under the Curve [AUC] of ANAVEX2-73

  7 weeks

Other Outcomes (6)

• Children's Sleep Habits Questionnaire (CSHQ)

  7 weeks

• Seizure Frequency via seizure diary

  7 weeks

• Genetic variant SIGMAR1, COMT

  7 weeks

Study Arms (2)

Active arm

EXPERIMENTAL

ANAVEX2-73 liquid oral solution

Drug: ANAVEX2-73

Placebo arm

PLACEBO COMPARATOR

Placebo liquid oral solution

Drug: Placebo

Interventions

ANAVEX2-73 DRUG

Liquid oral solution

Active arm

Placebo DRUG

Liquid oral solution

Placebo arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Anavex Life Sciences Corp.: lead

Study Sites (7)

HammondCare

Greenwich, New South Wales, 2065, Australia

Location

Mater Misericordiae Ltd

South Brisbane, Queensland, 4101, Australia

Location

Royal Melbourne Hospital (RMH)

Melbourne, Victoria, 3050, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

The Keogh Institute for Medical Research

Nedlands, Western Australia, 6009, Australia

Location

King's College of London

London, UK, SE5 8AF, United Kingdom

Location

Manchester CGM, St. Mary's Hospital

Manchester, UK, M13 9WL, United Kingdom

Location

MeSH Terms

Conditions

Rett Syndrome

Interventions

tetrahydro-N, N-dimethyl-2,2-diphenyl-3-furanmethanamine hydrochloride

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 36 participants: 3 PK open-label followed by 33 double-blind, randomized, placebo-controlled

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 8, 2019
• Study Start: May 6, 2019
• Primary Completion: September 30, 2021
• Study Completion: September 30, 2021
• Last Updated: January 27, 2022

Record last verified: 2022-01

Locations

AU (5); GB (2)