A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children Aged 2-14 Years With Dup15q Syndrome

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

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.

Study Overview

• Status: Terminated
• Conditions: Dup15q Syndrome
• Intervention / Treatment: Drug: Basmisanil; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Barcelona
    • Esplugues de Llobregas, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• United Kingdom
  • London, United Kingdom, SE1 7EH
    • Evelina London Children's Hospital
• United States
  • California
    • Los Angeles, California, United States, 90010
      • Children's Hospital Los Angeles
  • Illinois
    • Chicago, Illinois, United States, 60612-3244
      • Rush University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: Basmisanil; Participants will receive oral basmisanil at age-appropriate dosages
Placebo Comparator: 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).	Drug: Placebo; Participants will receive oral placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores	The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. Standard scores for the adaptive behavior composite range from 20-160; lower scores indicate lower adaptive functioning.	Baseline, Day 183, Day 365

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vineland-3 Gross and Fine Motor Subdomains Scores	The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the gross and fine motor domains range from 1-24; lower scores indicate lower adaptive functioning.	Baseline, Day 183, Day 365
Vineland 3 Expressive and Receptive Communication Subdomains	The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the expressive and receptive communication subdomains range from 1-24; lower scores indicate lower adaptive functioning.	Baseline, Day 183, Day 365
Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains	The Vineland-3 is an instrument that measures communication, daily living skills, socialization, and motor skills for those with intellectual and developmental disabilities. Items consist of open-ended questions related to activities and behavior and are scored as 2 = Usually, 1 = Sometimes, and 0 = Never. Items requiring a binary response are scored as 2 = Yes, 0. V-scale scores for the play and leisure time, and interpersonal relationships subdomains range from 1-24; lower scores indicate lower adaptive functioning.	Baseline, Day 153, Day 365
Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains	The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with total raw score ranges of 0-100 (gross motor) and 0-78 (fine motor). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.	Baseline, Day 183, Day 365
MSEL Visual Reception Domain Scores	The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50. Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.	Baseline, Day 183
MSEL Expressive and Receptive Language Subdomains	The MSEL are designed for a certified rater to provide an assessment of cognitive ability and motor development of typically developing children from birth through age 68 months. It was administered to all participants in this study irrespective of their chronological age. The instrument consists of 124 items across five scales measuring Gross Motor, Visual Reception, Fine Motor, Expressive Language, and Receptive Language. Each item is scored from 0-5 points with a total raw score range of 0-50 (expressive language) or 0-48 (receptive language). Lower score indicate lower developmental abilities; higher scores indicate greater developmental abilities.	Baseline, Day 183
Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores	The Dup15q CGI-S is a 10-domain clinician-rated measure on a 6-point scale that measures global severity of illness at a given point in time. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-none, 2-very mild, 3-mild, 4-moderate, 5-severe, and 6-very severe.	Baseline until Day 395, or early termination (prior to Day 395)
Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores	The Dup15q CGI-C is a 10-domain clinician-rated measure on a 7-point scale that assesses the clinician's impression of change in illness compared with baseline. The ten domains are seizures, expressive communication difficulties, fine motor skills difficulties, gross motor skills difficulties, cognitive/intellectual impairment, impairment in activities of daily living/self-care, socialization, maladaptive behavior, sleep difficulties, and overall severity. Response options are 1-very much improved, 2-much improved, 3-minimally improved, 4-no change, 5-minimally worse, 6-much worse, and 7-very much worse. The CGI does not yield a global score.	Day 28 - Day 395 or early termination (prior to Day 395)
Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability	The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The irritability domain score range is 0-45, with higher score indicating greater severity.	Baseline - Day 365, or early termination (prior to Day 365)
ABC-2-C Domain Scores - Social Withdrawal	The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The social withdrawal domain score range is 0-48, with higher scores indicating greater severity.	Baseline - Day 365, or early termination (prior to Day 365)
ABC-2-C Domain Scores - Stereotypic Behavior	The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The stereotypic behavior subdomain score range is 0-21, with higher scores indicating greater severity.	Baseline - Day 365, or early termination (prior to Day 365)
ABC-2-C Domain Scores - Hyperactivity/Non-Compliance	The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The hyperactivity/non-compliance subdomain score range is 0-45, with higher scores indicating greater severity.	Baseline until Day 365, or early termination (prior to Day 365)
ABC-2-C Domain Scores - Inappropriate Speech	The ABC-2 is an updated, empirically derived, validated 58-item caregiver-completed rating scale that measures the severity of a range of maladaptive behaviors commonly observed in children, adolescents, and adults with intellectual and developmental disabilities. The Community version of the scale (ABC-2-C) will be used. It is designed for use in individuals who are not residing in institutional settings. The checklist assesses symptoms across five domains: irritability, social withdrawal, stereotypic behavior, hyperactive/noncompliance, and inappropriate speech. Items are scored on a 4-point scale from 0 (never) to 3 (severe problem). The inappropriate speech subdomain score range is 0-12, with higher scores indicating greater severity.	Baseline until Day 365, or early termination (prior to Day 365)
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Up to 52 weeks
Plasma Concentration of Basmisanil		Day 1 - Day 183
Plasma Concentration of the Basmisanil Metabolite M1		Day 1 - Day 183
Quantitative EEG (qEEG) Beta-band Power	This is the average of the EEG parameter 10 x Log_10 of the total beta power between 16 and 32 Hz in microVolt^2.	Baseline, Day 14

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• https://forpatients.roche.com/

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2022
• Primary Completion (Actual): March 4, 2024
• Study Completion (Actual): March 4, 2024

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: dup15q; dup15q syndrome; 15q; duplication 15q; 15q duplication; chromosome 15q duplication; 15q duplication syndrome; duplication 15; triplication 15
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Polyposis Syndrome, Hereditary Mixed, 1; Chromosome 15q, trisomy; basmisanil
• Other Study ID Numbers: BP42992

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No