Dup15q syndrome Dup15q Syndrome neurodevelopment disorder
Conditions
Interventions
Basmisanil is a clinically characterized, brain penetrant, and highly selective 
negative allosteric modulator (NAM) of the GABAA a5R. Basmisanil has been 
developed for its high selectivity and specificity for the a5 -containing 
receptors versus the a1-, a2-, and a3-containing receptors, and is devoid of 
the anxiogenic and pro-convulsant liabilities of non-selective GABAA NAMs and 
antagonists.
The child receives one of two study treatments: Basmisanil or placebo. Study 
treatment is taken three times a day (morning, afternoon and evening, at least 
4 hours apart) from Day 2.
PART 1:
The doses depend on the age of the child on day 1:
- Doses: 240 mg for children 2- 5 years of age
- Doses: 320 mg for children aged 6-14 years
The doses depend on
with soft food such as yogurt, apple sauce or pudding.
Furthermore please refer to the Basmisanil Investigator's Brochure.
Sponsors
Roche Nederland B.V.
Eligibility
Age
2 Years to 15 Years
Inclusion criteria
Inclusion criteria: PART 1 • Participants aged 2 to 14 years inclusive at the time the caregiver signs the informed consent. • 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 Clinician Global Impression of Severity scale (Dup15q CGI-S) overall severity score >= 4 (at least moderately ill) • Stage 1 specific inclusion criterion: Participants aged 6 to 14 years with epilepsy. • Body weight equal to or above the third percentile for age • Male and female participants: Some of the provisions that follow may have limited applicability based on the age range of study participants (i.e., up to the age of 14) and the nature of the disease under study • Female Participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding • Male Participants: Male contraception is not required in this study because of the minimal seminal dose transmitted through sexual intercourse • The 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 for Harmonisation and local regulations • The 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 • The 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. PART 2: All participants who complete the 52 weeks of study treatment in Part 1 will be offered the option to roll over into an OLE to receive basmisanil treatment for a duration of approximately 2 years (Part 2). Participants will be required to sign a separate ICF for participation in Part 2.
Exclusion criteria
Exclusion criteria: PART 1 • Uncontrolled epilepsy at Screening as indicated by: Use of rescue medication(s) to treat more than one seizure cluster per month on average in the past 6 months; OR Concomitant chronic use of more than 4 anti-epileptic medications or status epilepticus within the past 6 months requiring hospitalization for treatment of the status epilepticus; OR any implanted devices to treat drug-resistant epilepsy • 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, including an average triplicate QTcF > 450 ms for participants > 10 years or QTcB > 450 ms for children up to and including age 10 years • Clinically significant abnormalities in laboratory test results at screening (including positive results for HIV, hepatitis B and/or hepatitis C). ALT values > 1.5 × the upper limit of normal. GFR < 90 mL/min per 1.73 m2 (Grade 1 CKD) as estimated using Schwarz formula. • 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 • 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 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. PART 2 A participant will not be eligible to receive study treatment after the end of Part 1 of the study if any of the following conditions are met: • The study treatment is commercially marketed in the participant's country and is reasonably accessible to the participant (e.g., is covered by the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PART 1 Primary: • Vineland-3: Adaptive Behavior Composite PART 2 Safety: • Incidence, nature, and severity of AEs and SAEs • Incidence of treatment discontinuations due to AEs • Incidence of laboratory abnormalities based on hematology, clinical chemistry, and urinalysis test results • ECG changes from baseline; incidence of abnormal ECG assessments • Change from baseline in all seizure frequency, duration, and type as reported in a seizure diary by caregivers • Abnormal changes in EEG recordings compared to baseline with a focus on treatment emergent epileptiform abnormalities • Systolic and diastolic blood pressure and heart rate measurements • Suicidality as assessed through questions from selected items adapted from the C CASA in participants aged 6 years and above • Height, weight, head circumference • Tanner staging over time (in participants aged 9 years and above) For other endpoints, please see protocol section 3. | — |
Secondary
| Measure | Time frame |
|---|---|
| See protocol section 3 | — |
Countries
Netherlands
Outcome results
None listed