Angelman Syndrome
Conditions
Brief summary
The purpose of the study is to assess the safety and tolerability of oral OV101 (gaboxadol) in adult and adolescent subjects with Angelman syndrome. In addition, several exploratory efficacy outcome measures will be investigated.
Detailed description
Two dosing schedules of OV101 (gaboxadol) giving as once daily or twice daily dose will be assessed against placebo.
Interventions
DRUGOV101 Regimen 1
DRUGOV101 regimen 2
OTHERPlacebo
Sponsors
Healx AI
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
13 Years to 49 Years
Healthy volunteers
No
Inclusion criteria
1. Age 13- 49 years 2. Diagnosis of Angelman syndrome 3. Receiving a stable regimen of concomitant medications for at least 4 weeks prior to Baseline, and able to maintain these throughout the duration of the study 4. Has a caregiver capable of providing informed consent on behalf of the subject and able to attend scheduled study visits 5. Able to ingest study medication 6. Caregivers must agree not to post any subject or study information on social media
Exclusion criteria
1. Unable to perform the study related safety and exploratory efficacy assessments, such as motor function 2. Poorly controlled seizure activity 3. Concomitant cardiovascular, respiratory, liver, renal, or hematologic diseases of a degree that would limit participation in the study 4. Pregnancy or women of child-bearing potential who are not using and acceptable method of contraception 5. Concomitant use of minocycline, levodopa, zolpidem, zaleplon, eszopiclone, ramelteon, and cannabinoid derivatives, or any other use of any investigational agent, device, and/or investigational procedure 4 weeks prior to Baseline and during the study 6. Allergy to OV101 or any excipients 7. At increased risk of harming self and/or others based on investigator assessment 8. Any condition or reason that in the opinion of the investigator makes the subject unsuitable for enrollment 9. Inability of subject or caregiver to comply with study requirements Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events in Placebo and Active Treatment Groups | Baseline and Week 12 | Summary of Subjects Reporting at least one Treatment Emergent Adverse Event (TEAEs), Safety Set. The table below summarizes the subjects who experienced TEAEs in the study. |
Countries
Israel, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo BID Evening and Morning | 29 |
| OV101 QD OV101 15 mg Evening Placebo in the Morning | 29 |
| OV101 BID OV101 15 mg Evening OV101 10 mg Morning | 29 |
| Total | 87 |
Baseline characteristics
| Characteristic | Placebo | OV101 QD | OV101 BID | Total |
|---|---|---|---|---|
| Age, Continuous Age at Inform Consent | 22.0 years STANDARD_DEVIATION 6.7 | 23.1 years STANDARD_DEVIATION 7.76 | 22.8 years STANDARD_DEVIATION 6.51 | 22.6 years STANDARD_DEVIATION 6.95 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 5 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 23 Participants | 23 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Gender Famale | 14 Participants | 9 Participants | 11 Participants | 34 Participants |
| Gender Male | 15 Participants | 20 Participants | 18 Participants | 53 Participants |
| Sex: Female, Male Female | 14 Participants | 9 Participants | 11 Participants | 34 Participants |
| Sex: Female, Male Male | 15 Participants | 20 Participants | 18 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 29 | 0 / 29 |
| other Total, other adverse events | 13 / 29 | 18 / 29 | 19 / 29 |
| serious Total, serious adverse events | 0 / 29 | 1 / 29 | 1 / 29 |
Outcome results
Primary
Incidence of Adverse Events in Placebo and Active Treatment Groups
Summary of Subjects Reporting at least one Treatment Emergent Adverse Event (TEAEs), Safety Set. The table below summarizes the subjects who experienced TEAEs in the study.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Drug-related TEAE | 13 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE | 25 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Serious TEAE | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE Leading to Study Withdrawal | 1 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Mild TEAE | 23 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE leading to Dose Change or Interruption | 5 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Severe TEAE | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Life-Threatening TEAE | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Moderate TEAE | 9 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Life-Threatening TEAE | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Mild TEAE | 23 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Drug-related TEAE | 18 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Serious TEAE | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE leading to Dose Change or Interruption | 5 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE | 27 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Severe TEAE | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE Leading to Study Withdrawal | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Moderate TEAE | 15 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE Leading to Study Withdrawal | 3 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Moderate TEAE | 9 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE | 25 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Mild TEAE | 23 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Severe TEAE | 4 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Life-Threatening TEAE | 0 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Drug-related TEAE | 19 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any TEAE leading to Dose Change or Interruption | 8 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Any Serious TEAE | 1 Participants |
Primary
Incidence of Adverse Events in Placebo and Active Treatment Groups
The Treatment Emergent Adverse Event (TEAEs) Reported by ≥10% of Subjects in Any Treatment Group by Preferred Term, Safety Set.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Vomiting | 9 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 5 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Pyrexia | 2 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 3 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Diarrhoea | 3 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Upper respiratory tract infection | 4 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 5 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 TEAE | 25 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 1 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nasopharyngitis | 5 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 4 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 4 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 2 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 2 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Diarrhoea | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Vomiting | 5 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nasopharyngitis | 2 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 3 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Pyrexia | 7 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 4 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Upper respiratory tract infection | 5 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 3 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 TEAE | 27 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 5 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nasopharyngitis | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Upper respiratory tract infection | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 TEAE | 25 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 3 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 5 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Pyrexia | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 3 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Diarrhoea | 3 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 4 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Vomiting | 5 Participants |
Primary
Incidence of Adverse Events in Placebo and Active Treatment Groups
Treatment-related TEAEs (Treatment Emergent Adverse Event) in ≥ 2 Subjects in OV101 Combined, Safety Set. The incidence of TEAEs assessed as treatment-related (at least possibly related to study drug, by the Investigator). Preferred Term in the table below.
Time frame: Baseline and Week 12
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 5 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Fatigue | 2 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Tremor | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonic epilepsy | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Anxiety | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sedation | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonus | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 Treatment-related TEAE | 13 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Lethargy | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Agitation | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 2 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Enuresis | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Insomnia | 1 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 2 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 2 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sleep disorder | 0 Participants |
| Placebo | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 3 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sleep disorder | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Fatigue | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonus | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 2 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 Treatment-related TEAE | 18 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 5 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonic epilepsy | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Lethargy | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sedation | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Tremor | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 4 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Insomnia | 2 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Agitation | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Anxiety | 0 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Enuresis | 1 Participants |
| OV101 QD | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Decreased appetite | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Fatigue | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Irritability | 4 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Aggression | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Nausea | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Rash | 0 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Insomnia | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | At least 1 Treatment-related TEAE | 19 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Enuresis | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Agitation | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Seizure | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sleep disorder | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Lethargy | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonic epilepsy | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Myoclonus | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Sedation | 1 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Somnolence | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Anxiety | 2 Participants |
| OV101 BID | Incidence of Adverse Events in Placebo and Active Treatment Groups | Tremor | 1 Participants |