A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children Aged 2-14 Years With Dup15q Syndrome
- Registration Number
- NCT05307679
- Lead Sponsor
- Hoffmann-La Roche
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will receive oral placebo BID on the first day of treatment, then TID until the end of Part 1 of the trial (Day 365). Basmisanil Basmisanil Participants will receive oral basmisanil twice daily (BID) on the first day of treatment, then three times per day (TID) until the end of Part 1 of the trial (Day 365) or the end of Part 2 (Day 1095)
- Primary Outcome Measures
Name Time Method Vineland-3 adaptive behavior composite scores Up to 52 weeks
- Secondary Outcome Measures
Name Time Method Vineland-3 gross and fine motor subdomains scores Up to 52 weeks Mullen Scales of Early Learning (MSEL) gross and fine motor domains Up to 52 weeks MSEL visual reception domain scores Up to 52 weeks MSEL expressive and receptive language subdomains Up to 52 weeks Vineland 3 expressive and receptive communication subdomains Up to 52 weeks Dup15q syndrome Clinician Global Impression of Change scale (CGI-C) scores Up to 52 weeks Vineland-3 play and leisure time and interpersonal relationships subdomains Up to 52 weeks Dup15q syndrome Clinician Global Impression of Severity (CGI-S) scale scores Up to 52 weeks Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) domain scores Up to 52 weeks Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to 52 weeks Incidence of treatment discontinuations due to AEs Up to 52 weeks Incidence of laboratory abnormalities based on hematology, clinical chemistry, and urinalysis test results Up to 52 weeks ECG QTc interval changes from baseline Up to 52 weeks Incidence of abnormal electrocardiogram (ECG) assessments Up to 52 weeks Change from baseline in seizure frequency, duration, and type Up to 52 weeks Abnormal changes in EEG recordings compared to baseline with a focus on treatment-emergent epileptiform abnormalities Up to 52 weeks Systolic and diastolic blood pressure measurements Up to 52 weeks Heart rate measurements Up to 52 weeks Suicidality as assessed through questions from selected items adapted from the Columbia Classification Algorithm for Suicide (C-CASA) in participants aged 6 years and above Up to 52 weeks Height in meters (m) Up to 52 weeks Weight in kilograms (kg) Up to 52 weeks Head circumference in centimeters (cm) Up to 52 weeks Tanner staging over time in participants aged 9 years and above Up to 52 weeks Plasma concentration of basmisanil Up to 52 weeks Plasma concentration of the basmisanil metabolite M1 Up to 52 weeks Area under the concentration-time curve during one dosing interval at steady state (AUCtau,ss) of basmisanil Up to 52 weeks Maximum concentration at steady state (Cmax,ss) of basmisanil Up to 52 weeks Trough plasma concentration at steady state (Ctrough, ss) of basmisanil Up to 52 weeks Apparent clearance (CL/F) of basmisanil Up to 52 weeks Apparent volume of distribution (Vd/F) of basmisanil Up to 52 weeks Plasma concentration ratio of M1 to basmisanil at trough Up to 52 weeks Cmax,ss of M1 Up to 52 weeks Ctrough, ss of M1 Up to 52 weeks Quantitative EEG (qEEG) beta-band power Up to 52 weeks
Trial Locations
- Locations (11)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Rady Children's Hospital - San Diego
🇺🇸San Diego, California, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
CHULC, E.P.E. - Hospital Dona Estefania; Servico de Neuropediatria
🇵🇹Lisboa, Portugal
University of North Carolina At Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
🇵🇱Pozna?, Poland
Hospital Sant Joan De Deu
🇪🇸Esplugues De Llobregas, Barcelona, Spain
Hospital Universitario La Paz; Servicio de Neurologia
🇪🇸Madrid, Spain
Evelina London Children's Hospital
🇬🇧London, United Kingdom
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain