Trial summary

This study will evaluate the safety, efficacy, and pharmacodynamics of 52 weeks of basmisanil
treatment in children with Dup15q syndrome aged 2 to 11 years. The study will test the
hypothesis that modulation of a GABAA receptor subtype can address excessive receptor
function and positively impact core neurodevelopmental disease features in children with
Dup15q syndrome.

Broad Health Condition

Specific Health ConditionDup15q Syndrome

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
QLD,

Hospital
Queensland Children?s Hospital

Phase of TrialPhase 2

Key inclusion criteria

Inclusion Criteria:

    -  Documented maternal duplication (3 copies) or triplication (4 copies) of the
       chromosome 15q11.2-q13.1 region that includes the Prader Willi/Angelman critical
       region defined as [BP2-BP3] segment

    -  Dup15q syndrome Clinical Global Impression Severity scale (Dup15q CGI-S) overall
       severity score = 4 (at least moderately ill)

    -  Body weight equal to or above the third percentile for age

    -  Participant has a parent, caregiver, or legally authorized representative (hereinafter
       "caregiver") of at least 18 years of age, who is fluent in the local language at the
       site, and capable and willing to provide written informed consent for the participant,
       according to International Council on Harmonisation and local regulations

    -  Participant's caregiver must be living with the participant and, in the opinion of the
       Investigator, able and willing to reliably assess the participant's ongoing condition,
       to accompany the participant to all clinic visits, and ensure compliance to study
       treatment throughout the study. The same caregiver is able and willing to complete the
       caregiver assessments and is available to the Investigational Site by telephone or
       email if needed

    -  Participant's caregiver is able and willing to use electronic devices to record
       information on the participant's condition and to complete assessments at home and
       agrees to home nursing visits, if local regulations allow for it and if home nursing
       service is available in the country/region

  Exclusion Criteria:

    -  Uncontrolled epilepsy at screening (as defined by the protocol)

    -  Lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell
       or squamous epithelial carcinomas of the skin that have been resected with no evidence
       of metastatic disease for 3 years

    -  Clinically significant ECG abnormalities at Screening

    -  Clinically significant abnormalities in laboratory test results at screening
       (including positive results for HIV, hepatitis B and/or hepatitis C)

    -  Allowed prior existing medication should be on a stable regimen (or frequency of
       intervention) for at least 6 weeks, and at least 8 weeks for anti-epileptic treatment,
       prior to Screening

    -  Non-pharmacological / behavioral therapies should not be stopped or newly started at
       least 6 weeks prior to Screening and are expected to remain stable for the entire
       study duration (excluding changes related to standard age and educational
       interventional programs and minor interruptions such as illness or vacation

    -  Concomitant use of prohibited medications

    -  Participation in an investigational drug study within one month or within 6 × the
       elimination half-life, whichever is longer, prior to dosing in the study

    -  Significant risk for suicidal behavior, as assessed through the suicidal behavior
       question adapted from the Columbia Classification Algorithm for Suicide Assessment
       (C-CASA) (participants = 6 years of age only)

    -  Known sensitivity to any of the study treatments or components thereof or drug or
       other allergy that, in the opinion of the Investigator, contraindicates the
       participation in the study, including severe lactose intolerance (e.g., unable to
       tolerate 250 mL [8 oz. or 1 cup] of milk, ice cream, or yogurt)

    -  Concomitant clinically relevant disease or condition or any clinically significant
       finding at screening that could interfere with, or for which, the treatment might
       interfere with, the conduct of the study or that would pose an unacceptable risk to
       the participants in this study

    -  Known active or uncontrolled bacterial, viral, or other infection (excluding fungal
       infections of nail beds) or any major clinically significant episode of infection or
       hospitalization (relating to the completion of the course of antibiotics) within 6
       weeks prior to the start of drug administration

Minimum age2 Years

Maximum age11 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

The Global Angelman Syndrome Registry is an online patient organisation driven registry to
collect information about the natural history of children and adults with Angelman Syndrome.
The registry will facilitate 1) recruitment for clinical trials into therapies and
interventions to benefit participants with Angelman Syndrome and their families, and 2)
advancement of research and best standards of care for Angelman Syndrome.

The registry is currently available in English, Spanish, Traditional Chinese and Italian.

Broad Health ConditionAngelman Syndrome
Registries
Observational study only

Specific Health ConditionAngelman Syndrome

Recruitment statusRecruiting

Recruitment Details
Recruitment State
QLD,

Key inclusion criteria

Inclusion Criteria:

    -  Diagnosis of Angelman Syndrome

  Exclusion Criteria:

  -

GenderAll

Can Healthy volunteers participate?No

Trial summary

The purpose of this study is to evaluate the safety and tolerability of ascending doses of
ION582 administered intrathecally in participants with Angelman syndrome.

Broad Health Condition

Specific Health ConditionAngelman Syndrome

Trial FocusTreatment

Recruitment statusRecruiting

Phase of TrialPhase 1/Phase 2

Key inclusion criteria

Inclusion Criteria:

    1. Participant has a documented and certified diagnosis of Angelman syndrome (AS)
       (ubiquitin-protein ligase E3A [UBE3A] deletion or UBE3A mutation)

    2. Male or female between the ages of 2-50 years of age, with signed informed consent
       from parent(s) or legal guardian(s)

    3. Currently receiving stable standard of care treatments such as, stable doses of
       anti-epileptic medication, behavioral management medications, sleep medications,
       gabapentin, cannabidiol, and including special diets, supplements or nutritional
       support for at least 3 months prior to first dose.

    4. Follow good study practice and not participate in the sharing of personal or study
       information on social media platforms, such as any website or social media site (e.g.,
       Facebook, Instagram, Twitter, YouTube, etc.) until notified that the study is
       completed.

  Exclusion Criteria:

    1. Has documented molecular AS confirmation of paternal uniparental disomy (UPD) or
       imprinting defect (ID).

    2. Any clinically significant (CS) cardiovascular, endocrine, hepatic, renal, pulmonary,
       gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition
       that, in the judgment of the Investigator, will pose a safety risk, will make the
       patient unsuitable for participation in, and/or unable to complete the study
       procedures. Has poorly controlled seizures as determined by the Investigator or has
       documented Status Epilepticus in the past 6 months that could pose a safety risk while
       on study.

    3. Known bone, spine, bleeding, or other disorder that exposes the patient to risk of
       injury or unsuccessful lumbar puncture. Previous treatment with an oligonucleotide
       (including small interfering ribonucleic acid, antisense oligonucleotide [ASOs]).
       COVID-19 vaccinations are allowed.

    4. Any prior use of gene therapy. Have any other conditions, which, in the opinion of the
       Investigator would make the participant unsuitable for inclusion or could interfere
       with the participant taking part in or completing the study.

Minimum age2 Years

Maximum age50 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

A study of the safety, tolerability and pharmacokinetics of NNZ-2591 and measures of efficacy
in children and adolescents with Angelman syndrome

Broad Health ConditionAngelman Syndrome

Specific Health ConditionAngelman Syndrome

Trial FocusTreatment

Recruitment statusRecruiting

Recruitment Details
Recruitment State
NSW,QLD,VIC,

Hospital
Sydney Children's Hospital

Hospital
Centre for Clinical Trials in Rare Neurodevelopmental Disorders at Children's Health Queensland Hospital and Health Service

Phase of TrialPhase 2

Key inclusion criteria

Inclusion Criteria:

    1. Clinical diagnosis of AS with a documented disease-causing genetic etiology known to
       impact maternally derived UBE3A expression in brain.

    2. Males or females aged 3-17 years

    3. Body Weight of >12Kg

    4. Subjects with a Clinical Global Impression - Severity (CGI-S) score of 3 or greater

    5. Not actively undergoing regression or loss of skills, defined as no persistent loss of
       previously acquired developmental skills for a period within 3 months of the Screening
       visit

    6. Each subject must be able to swallow the study medication provided as a liquid
       solution.

    7. Caregiver(s) must have sufficient English language skills.

  Exclusion Criteria:

    1. Mosaicism for disease-causing mutation.

    2. Clinically Significant abnormalities in safety laboratory testing or vital signs at
       screening

    3. Abnormal QTcF interval or prolongation at Screening.

    4. Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and previous
       COVID 19 infection with last 12 months that required hospitalization.

    5. Unstable or changes to Psychotropic treatment 2 weeks prior to screening .

    6. Excluded concomitant treatments

    7. Actively undergoing regression or loss of skills.

    8. Unstable seizure profile.

    9. Current clinically significant renal conditions and abnormalities

   10. Current clinically significant cardiovascular, hepatic, gastrointestinal, respiratory,
       endocrine disease, or clinically significant organ impairment.

   11. Current clinically significant hypo or hyperthyroidism, Type 1 or Type 2 diabetes
       mellitus requiring insulin (whether well controlled or uncontrolled), or uncontrolled
       Type 1 or Type 2 diabetes.

   12. Has planned surgery during the study.

   13. History of, or current, cerebrovascular disease or brain trauma.

   14. History of, or current catatonia or catatonia-like symptoms.

   15. History of, or current, malignancy.

   16. Current major or persistent depressive disorder (including bipolar depression).

   17. Significant, uncorrected visual or uncorrected hearing impairment.

   18. Allergy to strawberry.

   19. Positive pregnancy test

   20. Subject is judged by the Investigator or Medical Monitor to be inappropriate for the
       study

Minimum age3 Years

Maximum age17 Years

GenderAll

Can Healthy volunteers participate?No

Trial summary

The primary objective of the study is to evaluate the safety and tolerability of
multiple-ascending doses of GTX-102 administered by intrathecal (IT) injection to patients
with Angelman Syndrome (AS).

Broad Health Condition

Specific Health ConditionAngelman Syndrome

Trial FocusTreatment

Recruitment statusRecruiting

Phase of TrialPhase 1/Phase 2

Key inclusion criteria

Key Inclusion Criteria:

    -  Signed informed consent from parent(s) or legal guardian(s)

    -  Documented genetic confirmation of full maternal UBE3A gene deletion causing AS (e.g.
       DNA methylation testing with either a chromosomal microarray or FISH) in the region of
       15q11.2-q13 including class I, II or III).

    -  Age = 4 to = 17 years at screening (in US Age = 4 to < 8 years at screening)

    -  Stable seizure control (defined as clinically stable with no changes in antiepileptic
       medications over the prior 1 month before screening visit, other than weight
       associated dose adjustments)

    -  Platelet count, prothrombin time (PT) / international normalized ratio (INR) and
       partial thromboplastin time (PTT) within normal limits

    -  Normal renal function with serum creatinine and spot urine protein within normal
       limits

    -  Normal hepatic function with total bilirubin, aspartate aminotransferase (AST),alanine
       aminotransferase (ALT) and alkaline phosphatase within normal limits

    -  Willing and able to comply with scheduled visits, drug administration plan, laboratory
       tests, study restrictions, and all study procedures LP.

    -  Able to tolerate the anesthetic regimen required for LP procedure

  Key Exclusion Criteria:

    -  Any change in medications (excluding antiepileptic drugs) or diet intended to treat
       symptoms of AS (e.g. sleeping aids, supplements, ketogenic or low-glycemic index diet,
       other) over the prior 1 month before screening.

    -  Inability to ambulate independently or with an assistive device or caregiver hand-hold

    -  Any bleeding or platelet disorder

    -  Any clinically significant cardiovascular, endocrine, hepatic, renal, pulmonary,
       gastrointestinal, neurologic, malignant, metabolic, psychiatric, or other condition
       that, in the judgment of the Investigator, will pose a safety risk, will make the
       patient unsuitable for participation in, and/or unable to complete the study
       procedures.

    -  Any laboratory abnormality, that, in the Investigator's opinion, could adversely
       affect the safety of the patient, make it unlikely that the course of treatment or
       follow up would be completed, or impair the assessment of study result

    -  Any active infection

    -  Bone, spine, bleeding, or other disorder that exposes the patient to risk of injury or
       unsuccessful lumbar puncture

    -  Drugs that increase the risk of bleeding (e.g. heparin, low molecular weight heparin,
       platelet inhibitors).

    -  Use of any investigational oligonucleotide in the past 6 months (with the exception of
       GTX-102)

    -  Any prior use of gene therapy

    -  Use of any investigational drugs in the past 6 months (with the exception of GTX-102)

    -  Any medical condition that would require intubation for the anesthesia procedure

         -  NOTE: Additional Inclusion/Exclusion Criteria may apply

Minimum age4 Years

Maximum age17 Years

GenderAll

Can Healthy volunteers participate?No