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

Hoffmann-La Roche5 sites in 3 countries7 target enrollmentDecember 16, 2022

ConditionsDup15q Syndrome

InterventionsBasmisanil Placebo

DrugsBasmisanil Placebo

Overview

Phase: Phase 2
Intervention: Basmisanil
Conditions: Dup15q Syndrome
Sponsor: Hoffmann-La Roche
Enrollment: 7
Locations: 5
Primary Endpoint: Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores
Status: Terminated
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

December 16, 2022

End Date

March 4, 2024

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

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)

Arms & Interventions

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)

Intervention: Basmisanil

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).

Intervention: Placebo

Outcomes

Primary Outcomes

Vineland-3 Adaptive Behavior Scales, 3rd Edition Composite Scores

Time Frame: Baseline, Day 183, Day 365

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.

Secondary Outcomes

Vineland-3 Gross and Fine Motor Subdomains Scores(Baseline, Day 183, Day 365)
Vineland 3 Expressive and Receptive Communication Subdomains(Baseline, Day 183, Day 365)
Mullen Scales of Early Learning (MSEL) Gross and Fine Motor Domains(Baseline, Day 183, Day 365)
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(Baseline, Day 14)
Vineland-3 Play and Leisure Time and Interpersonal Relationships Subdomains(Baseline, Day 153, Day 365)
Dup15q Syndrome Clinician Global Impression of Change Scale (CGI-C) Scores(Day 28 - Day 395 or early termination (prior to Day 395))
Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) Domain Scores - Irritability(Baseline - Day 365, or early termination (prior to Day 365))
MSEL Visual Reception Domain Scores(Baseline, Day 183)
MSEL Expressive and Receptive Language Subdomains(Baseline, Day 183)
Dup15q Syndrome Clinician Global Impression of Severity (CGI-S) Scale Scores(Baseline until Day 395, or early termination (prior to Day 395))
ABC-2-C Domain Scores - Social Withdrawal(Baseline - Day 365, or early termination (prior to Day 365))
ABC-2-C Domain Scores - Stereotypic Behavior(Baseline - Day 365, or early termination (prior to Day 365))
ABC-2-C Domain Scores - Hyperactivity/Non-Compliance(Baseline until Day 365, or early termination (prior to Day 365))
ABC-2-C Domain Scores - Inappropriate Speech(Baseline until Day 365, or early termination (prior to Day 365))
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)(Up to 52 weeks)