A Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of 52 weeks of Treatment with Basmisanil in Children with Dup15q Syndrome.
- Conditions
- Dup15q SyndromeMedDRA version: 23.0Level: LLTClassification code 10083952Term: Dup15q syndromeSystem Organ Class: 100000004850Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2021-003791-13-IT
- Lead Sponsor
- F. HOFFMANN - LA ROCHE LTD.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 90
• Participants aged 2 to 11 years inclusive at the time the caregiver signs the informed consent (for Stage 1, participants aged 6 to 11 years inclusive; for Stage 2, participants aged 2 to 5 years inclusive; and for Stage 3, participants aged 2 to 11 years inclusive)
• 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 Clinical Global Impression Severity scale (Dup15q CGI-S) overall severity score >_ 4 (at least moderately ill)
• Stages 1 and 2: Participants with epilepsy only
• 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 11) 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 on 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.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
• Individuals with known pathogenic mutations or copy number variants, of established neurodevelopmental significance, other than duplication or triplication of the chromosome 15q11.2-q13.1
• Uncontrolled epilepsy at Screening as indicated by: Use of rescue medication more than once per month on average in the past 6 months or concomitant use of more than 4 anti-epileptic medications or status epilepticus within the past 6 months requiring urgent hospitalization 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
• 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, in the opinion of the Investigator as assessed by suicidality questions adapted from the Columbia Classification Algorithm for Suicide (C-CASA)
• 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the effects of basmisanil treatment on core symptom domains of Dup15q syndrome (language and social skills) and daily functioning.;Secondary Objective: • To evaluate the effects of basmisanil treatment on Motor function, Cognition, Language, Social skills, Clinical impression of global functioning, Challenging behaviors<br>• To evaluate the tolerability and safety of 52 weeks treatment of basmisanil<br>• To characterize the PK of basmisanil and its metabolite M1 and determine the dose that will deliver target exposure in participants aged 2-11 years<br>• To evaluate potential relationships between selected covariates and exposure to basmisanil<br>• To evaluate the effects of basmisanil treatment on the characteristic Dup15q EEG phenotype acutely and at steady state.;Primary end point(s): 1. Vineland Adaptive Behavior Scale–Third Edition (Vineland-3): Adaptive Behavior Composite.;Timepoint(s) of evaluation of this end point: 1. Baseline (Day -7 to Day -1), Day 183, Day 365.
- Secondary Outcome Measures
Name Time Method