a study to evaluate the safety and efficacy of basmisanil treatment in children aged 2-14 years with dup15q syndrome

Conditions: Dup15q Syndrome

Summary: this study consists of two parts. part 1 will evaluate the safety, efficacy, and pharmacodynamics of 52-weeks of basmisanil treatment in children and adolescents (aged 2-14 years) with dup15q syndrome. part 1 will test the hypothesis that negative allosteric modulation of a gabaa receptor subtype can address excessive receptor function and positively impact core neurodevelopmental disease feature in individuals with dup15q syndrome. part 2 is an optional 2-year open-label extension to evaluate long-term safety, tolerability, and to provide supportive evidence of benefit of continued treatment with basmisanil in selected efficacy outcomes.


Eligibility 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 clinician global impression of 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 for 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

Keywords: dup15q dup15q syndrome 15q duplication 15q 15q duplication chromosome 15q duplication 15q duplication syndrome duplication 15 triplication 15