Clinical trial NCT05307679: A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children Aged 2-14 Years With Dup15q Syndrome
Official title: A Phase II, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Safety, Efficacy, and Pharmacodynamics of 52 Weeks of Treatment With Basmisanil in Participants Aged 2 to 14 Years Old With Dup15q Syndrome Followed by a 2-Year Optional Open-Label Extension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Dup15q Syndrome
Keywords: dup15q
dup15q syndrome
15q
duplication 15q
15q duplication
chromosome 15q duplication
15q duplication syndrome
duplication 15
triplication 15
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-04-01
Enrollment: 7
Sex: ALL
Minimum age (years): 2
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Vineland-3 adaptive behavior composite scores
timeFrame: Up to 52 weeks
Secondary outcomes:
measure: Vineland-3 gross and fine motor subdomains scores
timeFrame: Up to 52 weeks
measure: Mullen Scales of Early Learning (MSEL) gross and fine motor domains
timeFrame: Up to 52 weeks
measure: MSEL visual reception domain scores
timeFrame: Up to 52 weeks
measure: Vineland 3 expressive and receptive communication subdomains
timeFrame: Up to 52 weeks
measure: MSEL expressive and receptive language subdomains
timeFrame: Up to 52 weeks
measure: Vineland-3 play and leisure time and interpersonal relationships subdomains
timeFrame: Up to 52 weeks
measure: Dup15q syndrome Clinician Global Impression of Severity (CGI-S) scale scores
timeFrame: Up to 52 weeks
measure: Dup15q syndrome Clinician Global Impression of Change scale (CGI-C) scores
timeFrame: Up to 52 weeks
measure: Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) domain scores
timeFrame: Up to 52 weeks
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 52 weeks
measure: Incidence of treatment discontinuations due to AEs
timeFrame: Up to 52 weeks
measure: Incidence of laboratory abnormalities based on hematology, clinical chemistry, and urinalysis test results
timeFrame: Up to 52 weeks
measure: ECG QTc interval changes from baseline
timeFrame: Up to 52 weeks
measure: Incidence of abnormal electrocardiogram (ECG) assessments
timeFrame: Up to 52 weeks
measure: Change from baseline in seizure frequency, duration, and type
timeFrame: Up to 52 weeks
measure: Abnormal changes in EEG recordings compared to baseline with a focus on treatment-emergent epileptiform abnormalities
timeFrame: Up to 52 weeks
measure: Systolic and diastolic blood pressure measurements
timeFrame: Up to 52 weeks
measure: Heart rate measurements
timeFrame: Up to 52 weeks
measure: 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
timeFrame: Up to 52 weeks
measure: Height in meters (m)
timeFrame: Up to 52 weeks
measure: Weight in kilograms (kg)
timeFrame: Up to 52 weeks
measure: Head circumference in centimeters (cm)
timeFrame: Up to 52 weeks
measure: Tanner staging over time in participants aged 9 years and above
timeFrame: Up to 52 weeks
measure: Plasma concentration of basmisanil
timeFrame: Up to 52 weeks
measure: Plasma concentration of the basmisanil metabolite M1
timeFrame: Up to 52 weeks
measure: Area under the concentration-time curve during one dosing interval at steady state (AUCtau,ss) of basmisanil
timeFrame: Up to 52 weeks
measure: Maximum concentration at steady state (Cmax,ss) of basmisanil
timeFrame: Up to 52 weeks
measure: Trough plasma concentration at steady state (Ctrough, ss) of basmisanil
timeFrame: Up to 52 weeks
measure: Apparent clearance (CL/F) of basmisanil
timeFrame: Up to 52 weeks
measure: Apparent volume of distribution (Vd/F) of basmisanil
timeFrame: Up to 52 weeks
measure: Plasma concentration ratio of M1 to basmisanil at trough
timeFrame: Up to 52 weeks
measure: Cmax,ss of M1
timeFrame: Up to 52 weeks
measure: Ctrough, ss of M1
timeFrame: Up to 52 weeks
measure: Quantitative EEG (qEEG) beta-band power
timeFrame: Up to 52 weeks
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: San Diego
country: United States
facility: Rady Children's Hospital - San Diego
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chapel Hill
country: United States
facility: University of North Carolina At Chapel Hill
state: North Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Pozna?
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
city: Lisboa
country: Portugal
facility: CHULC, E.P.E. - Hospital Dona Estefania; Servico de Neuropediatria
city: Esplugues De Llobregas
country: Spain
facility: Hospital Sant Joan De Deu
state: Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Neurologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: London
country: United Kingdom
facility: Evelina London Children's Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: