A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children With Dup15q Syndrome

• ClinicalTrials.gov Identifier: NCT05307679
• Recruitment Status: Recruiting
• First Posted: April 1, 2022
• Last Update Posted: January 18, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

Brief Summary:

This study will evaluate the safety, efficacy, and pharmacodynamics of 52 weeks of basmisanil treatment in children with Dup15q syndrome aged 2 to 11 years. The study will test the hypothesis that modulation of a GABAA receptor subtype can address excessive receptor function and positively impact core neurodevelopmental disease features in children with Dup15q syndrome.

Condition or disease	Intervention/treatment	Phase
Dup15q Syndrome	Drug: Basmisanil; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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 Children With Dup15q Syndrome
• Actual Study Start Date: December 16, 2022
• Estimated Primary Completion Date: January 1, 2026
• Estimated Study Completion Date: January 1, 2026

Arms and Interventions

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 the trial on Day 365.	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 the trial on Day 365.	Drug: Placebo; Participants will receive oral placebo

Outcome Measures

Primary Outcome Measures :

1. Vineland-3 adaptive behavior composite scores [ Time Frame: Up to 61 weeks ]

Secondary Outcome Measures :

1. Vineland-3 scores [ Time Frame: Up to 61 weeks ]
2. Mullen Scales of Early Learning (MSEL) scores [ Time Frame: Up to 61 weeks ]
3. Dup15q syndrome Clinical Global Impression Change scale (CGI-C) scores [ Time Frame: Up to 61 weeks ]
4. Dup15q syndrome CGI Severity (CGI-S) scale scores [ Time Frame: Up to 61 weeks ]
5. Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) domain scores [ Time Frame: Up to 61 weeks ]
6. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Up to 61 weeks ]
7. Incidence of abnormal electrocardiogram (ECG) assessments [ Time Frame: Up to 61 weeks ]
8. Change from baseline in seizure frequency, duration, and type [ Time Frame: Up to 61 weeks ]
9. Incidence of treatment-emergent epileptiform abnormalities [ Time Frame: Up to 61 weeks ]
10. Suicidality as assessed through questions from selected items adapted from the Columbia Classification Algorithm for Suicide (C-CASA) [ Time Frame: Up to 61 weeks ]
11. Plasma concentration of basmisanil [ Time Frame: Up to 61 weeks ]
12. Plasma concentration of the basmisanil metabolite M1 [ Time Frame: Up to 61 weeks ]
13. Area under the concentration-time curve during one dosing interval at steady state (AUCtau,ss) of basmisanil [ Time Frame: Up to 61 weeks ]
14. Maximum concentration at steady state (Cmax,ss) of basmisanil [ Time Frame: Up to 61 weeks ]
15. Trough plasma concentration at steady state (Ctrough, ss) of basmisanil [ Time Frame: Up to 61 weeks ]
16. Apparent clearance (CL/F) of basmisanil [ Time Frame: Up to 61 weeks ]
17. Apparent volume of distribution (Vd/F) of basmisanil [ Time Frame: Up to 61 weeks ]
18. Plasma concentration ratio of M1 to basmisanil at trough [ Time Frame: Up to 61 weeks ]
19. Cmax,ss of M1 [ Time Frame: Up to 61 weeks ]
20. Ctrough, ss of M1 [ Time Frame: Up to 61 weeks ]
21. Quantitative EEG (qEEG) beta-band power [ Time Frame: Up to 61 weeks ]

Eligibility Criteria

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

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 Clinical Global Impression 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 on 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

Contacts and Locations

Contacts

Contact: Reference Study ID Number: BP42992 https://forpatients.roche.com/; 888-662-6728; global-roche-genentech-trials@gene.com

Locations

Australia, Queensland

Queensland Children's Hospital; Recruiting

South Brisbane, Queensland, Australia, 4101

Italy

IRCCS Oasi Maria SS.; Dipartimento per il ritardo mentale; Recruiting

Troina (EN), Sicilia, Italy, 94018

Fondazione Stella Maris; Dipartimento di neuroscienze dello sviluppo; Recruiting

Calambrone (pisa), Toscana, Italy, 56128

Spain

Hospital Sant Joan De Deu; Recruiting

Esplugues De Llobregas, Barcelona, Spain, 08950

United Kingdom

Evelina London Children's Hospital; Recruiting

London, United Kingdom, SE1 7EH

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT05307679
• Other Study ID Numbers: BP42992
• First Posted: April 1, 2022
• Last Update Posted: January 18, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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).

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Syndrome; Disease; Pathologic Processes