ANAVEX2-73 Study in Pediatric Patients With Rett Syndrome

NCT04304482 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: ANAVEX2-73-RS-003
• Study Type: interventional
• Target: 92
• Locations: 3 countries
• Sites: 12

Brief Summary

ANAVEX2-73-RS-003 is a Phase 2/3, double-blind, randomized, placebo-controlled dose escalation safety, tolerability and efficacy study in patients 5-17 years of age with RTT using endpoints including multiple clinical and exploratory molecular and biochemical measures.

Conditions

Rett Syndrome

Outcome Measures

Primary Outcomes (2)

• RSBQ

  Change from baseline to End of Treatment (EOT) in the Rett Syndrome Behaviour Questionnaire (RSBQ) Total score

  12 weeks

• Incidents of Adverse Events

  Change from baseline to End of Treatment (EOT)

  12 weeks

Secondary Outcomes (9)

• CGI-I

  12 weeks

• Anxiety, Depression, and Mood Scale (ADAMS)

  12 weeks

• Motor Behavioral Assessment-7 dynamic pediatric items (MBA-Ped7)

  12 weeks

• Children's Sleep Habits Questionnaire (CSHQ)

  12 weeks

• Seizure Frequency via seizure diary

  12 weeks

Other Outcomes (7)

• Glutamate Plasma Concentration

  12 weeks

• GABA Plasma Concentration

  12 weeks

• Genetic variant SIGMAR1, COMT

  12 weeks

Study Arms (2)

ANAVEX2-73 Active

EXPERIMENTAL

ANAVEX2-73 liquid oral solution

Drug: ANAVEX2-73 oral liquid

ANAVEX2-73 Placebo

PLACEBO COMPARATOR

Placebo liquid oral solution

Drug: Placebo oral liquid

Interventions

ANAVEX2-73 oral liquid DRUG

Liquid oral solution

Also known as: Blarcamesine

ANAVEX2-73 Active

Placebo oral liquid DRUG

Liquid oral solution

ANAVEX2-73 Placebo

Eligibility Criteria

• Age: 5 Years - 17 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Aged ≥ 5 years to 17 (inclusive).
• Diagnosis of classic RTT, according to 2010 criteria, and a MECP2 mutation.
• Post-regression stage, defined as ≥ 6 months since last loss of spoken language or motor (fine or gross) skills.
• Clinical Global Impression - Severity (CGI-S) score of 4 or greater at Screening.
• Current pharmacological treatment regimen, including supplements, has been stable for at least 4 weeks.
• If on 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/LAR will not electively initiate new or modify ongoing interventions for the duration of the study.
• The subject's caregiver/LAR is English-speaking and has sufficient language skills to complete the caregiver assessments and has the ability to keep accurate seizure diaries.
• If participant is a woman of childbearing potential (WOCBP#), a negative urine or serum pregnancy test is required to confirm she is not pregnant.
• 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.

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 or clinically evident 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., long QT) 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.
• Treatment with strong inhibitors or inducers of CYP3A4 or CYP2C19 is not stable (drug, dose) for 30 days prior to screening. Although these medications are not excluded, caution is advised when enrolling participants on potent CYP3A4 or CYP2C19 inducers or inhibitors (see respective section).
• Patients with hepatic and renal impairment.

Sponsors & Collaborators

• Anavex Life Sciences Corp.: lead
• Anavex Australia Pty Ltd.: collaborator
• Anavex Germany GmbH: collaborator

Study Sites (12)

The Children's Hospital at Westmead

Sydney, New South Wales, 2145, Australia

Location

Queensland Children's Hospital

Brisbane, Queensland, 4101, Australia

Location

Austin Health

Melbourne, Victoria, 3084, Australia

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Children's Hospital LHSC

London, Ontario, N6A 5W9, Canada

Location

Holland Bloorview Kids Hospital

Toronto, Ontario, M5H 3W4, Canada

Location

Royal Hospital for Children

Edinburgh, EH16 4TJ, United Kingdom

Location

Evelina London Children's Hospital

London, SE1 7EH, United Kingdom

Location

King's College of London

London, SE5 8AF, United Kingdom

Location

Manchester CGM, St Mary's Hospital

Manchester, M13 9WL, United Kingdom

Location

Nottingham University Hospital NHS Trust

Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (1)

• Heussler HS. Emerging Therapies and challenges for individuals with Angelman syndrome. Curr Opin Psychiatry. 2021 Mar 1;34(2):123-128. doi: 10.1097/YCO.0000000000000674.

  PMID: 33395098 DERIVED

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 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2020
• First Posted: March 11, 2020
• Study Start: July 1, 2020
• Primary Completion: June 1, 2023
• Study Completion: June 30, 2023
• Last Updated: August 21, 2023

Record last verified: 2023-08

Locations

GB (5); AU (3); CA (4)