Primary Disease or Condition Being Studied: Angelman Syndrome (AS)
Conditions
Brief summary
The purpose of this study is to assess the efficacy and safety of oral OV101 (gaboxadol) in pediatric subjects with Angelman syndrome.
Interventions
DRUGGaboxadol
OV101 versus placebo once daily at bedtime for 12 weeks
DRUGPlacebo
Matching placebo capsules to OV101 capsules.
Sponsors
Healx AI
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double (Participant/Care Giver and Investigator/Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
2 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male or female and 2 to 12 years old (inclusive) at the time of informed consent * Confirmed molecular diagnosis of AS * Has a CGI-S-AS score of 3 or more at baseline. * Meets the following age-appropriate body weight criterion: 1. Subjects 2 to 3 years old must have a minimum body weight of 9 kg. 2. Subjects 4 years and older must be between 17 kg and 64 kg (inclusive). * Stable concomitant mediations for at least 4 weeks before study start
Exclusion criteria
* Any condition that would limit study participation * Clinically significant lab or vital sign abnormalities at the time of screening * Poorly controlled seizures (weekly seizures of any frequency with a duration more than 3 minutes, weekly seizures occurring more than 3 times per week, each with a duration of less than 3 minutes, or as defined by investigator assessment) * Use of prescription medications for sleep, minocycline, or levodopa within the 4 weeks prior to Day 1 or during the study. Benzodiazepines chronically administered for seizure control are permitted. * Cannot comply with protocol study assessments during screening or caregiver unable to comply with study requirements. * Enrolled in any clinical trial or used any investigational agent within the 30 days before screening or concurrently with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 12 weeks | To evaluate the efficacy of OV101 versus placebo as assessed by the Clinical Global Impressions-Improvement-Angelman syndrome (CGI-I-AS) score at Week 12. CGIA-I-AS scores range from 1 (very much improved), to 4 (no change), to 7 (very much worse). |
Countries
Australia, Germany, Israel, Netherlands, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in the United States, Australia, Germany, Israel, and Netherlands.
Participants by arm
| Arm | Count |
|---|---|
| OV101 Once Daily (Weight-based Dosing) Age 4 to 12 OV101 (gaboxadol), oral, provided once daily at bedtime for 12 week duration
Gaboxadol: OV101 versus placebo once daily at bedtime for 12 weeks | 47 |
| Placebo Once Daily Matching placebo,oral, provided once daily at bedtime for 12 week duration
Placebo: Matching placebo capsules to OV101 capsules. | 50 |
| OV101 Once Daily (Weight-based Dosing) Age 2 to 3 OV101 (gaboxadol), oral, provided once daily at bedtime for 12 week duration | 7 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | OV101 Once Daily (Weight-based Dosing) Age 2 to 3 | Placebo Once Daily | OV101 Once Daily (Weight-based Dosing) Age 4 to 12 |
|---|---|---|---|---|
| Age, Customized 2-3 | 7 Participants | 7 Participants | 0 Participants | 0 Participants |
| Age, Customized 4-8 | 48 Participants | 0 Participants | 25 Participants | 23 Participants |
| Age, Customized 9-12 | 49 Participants | 0 Participants | 25 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 0 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 97 Participants | 7 Participants | 46 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Australia | 8 participants | 0 participants | 4 participants | 4 participants |
| Region of Enrollment Germany | 7 participants | 0 participants | 3 participants | 4 participants |
| Region of Enrollment Israel | 11 participants | 3 participants | 7 participants | 4 participants |
| Region of Enrollment Netherlands | 4 participants | 0 participants | 1 participants | 3 participants |
| Region of Enrollment United States | 67 participants | 4 participants | 35 participants | 32 participants |
| Sex: Female, Male Female | 46 Participants | 2 Participants | 20 Participants | 24 Participants |
| Sex: Female, Male Male | 58 Participants | 5 Participants | 30 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 50 | 0 / 7 |
| other Total, other adverse events | 31 / 47 | 22 / 50 | 4 / 7 |
| serious Total, serious adverse events | 1 / 47 | 0 / 50 | 0 / 7 |
Outcome results
Primary
Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks
To evaluate the efficacy of OV101 versus placebo as assessed by the Clinical Global Impressions-Improvement-Angelman syndrome (CGI-I-AS) score at Week 12. CGIA-I-AS scores range from 1 (very much improved), to 4 (no change), to 7 (very much worse).
Time frame: 12 weeks
Population: Total of 97 subjects, ages 4-12 years, inclusive. Participants aged 2 to 3 (n=7) did not participate in the scoring.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 3-Minimally improved | 11 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 5-Minimally worse | 1 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 2-Much improved | 11 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 6-Much worse | 1 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 4-No change | 22 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 7-Very much worse | 0 Participants |
| OV101 (Ages 4-12 Years, Inclusive) | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 1-Very much improved | 1 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 7-Very much worse | 0 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 1-Very much improved | 2 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 2-Much improved | 11 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 3-Minimally improved | 11 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 4-No change | 21 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 5-Minimally worse | 5 Participants |
| Placebo | Clinical Global Impressions- Improvement in Angelman Syndrome (CGI-I-AS) Rating at 12 Weeks | 6-Much worse | 0 Participants |