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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05307679




Registration number
NCT05307679
Ethics application status
Date submitted
25/03/2022
Date registered
1/04/2022
Date last updated
18/03/2024

Titles & IDs
Public title
A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children Aged 2-14 Years With Dup15q Syndrome
Scientific 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
Secondary ID [1] 0 0
BP42992
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dup15q Syndrome 0 0
Condition category
Condition code
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Basmisanil
Treatment: Drugs - Placebo

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)

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).


Treatment: Drugs: Basmisanil
Participants will receive oral basmisanil at age-appropriate dosages

Treatment: Drugs: Placebo
Participants will receive oral placebo
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Vineland-3 adaptive behavior composite scores
Timepoint [1] 0 0
Up to 52 weeks
Secondary outcome [1] 0 0
Vineland-3 gross and fine motor subdomains scores
Timepoint [1] 0 0
Up to 52 weeks
Secondary outcome [2] 0 0
Mullen Scales of Early Learning (MSEL) gross and fine motor domains
Timepoint [2] 0 0
Up to 52 weeks
Secondary outcome [3] 0 0
MSEL visual reception domain scores
Timepoint [3] 0 0
Up to 52 weeks
Secondary outcome [4] 0 0
Vineland 3 expressive and receptive communication subdomains
Timepoint [4] 0 0
Up to 52 weeks
Secondary outcome [5] 0 0
MSEL expressive and receptive language subdomains
Timepoint [5] 0 0
Up to 52 weeks
Secondary outcome [6] 0 0
Vineland-3 play and leisure time and interpersonal relationships subdomains
Timepoint [6] 0 0
Up to 52 weeks
Secondary outcome [7] 0 0
Dup15q syndrome Clinician Global Impression of Severity (CGI-S) scale scores
Timepoint [7] 0 0
Up to 52 weeks
Secondary outcome [8] 0 0
Dup15q syndrome Clinician Global Impression of Change scale (CGI-C) scores
Timepoint [8] 0 0
Up to 52 weeks
Secondary outcome [9] 0 0
Aberrant Behavior Checklist - Second Edition - Community Version (ABC-2-C) domain scores
Timepoint [9] 0 0
Up to 52 weeks
Secondary outcome [10] 0 0
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Timepoint [10] 0 0
Up to 52 weeks
Secondary outcome [11] 0 0
Incidence of treatment discontinuations due to AEs
Timepoint [11] 0 0
Up to 52 weeks
Secondary outcome [12] 0 0
Incidence of laboratory abnormalities based on hematology, clinical chemistry, and urinalysis test results
Timepoint [12] 0 0
Up to 52 weeks
Secondary outcome [13] 0 0
ECG QTc interval changes from baseline
Timepoint [13] 0 0
Up to 52 weeks
Secondary outcome [14] 0 0
Incidence of abnormal electrocardiogram (ECG) assessments
Timepoint [14] 0 0
Up to 52 weeks
Secondary outcome [15] 0 0
Change from baseline in seizure frequency, duration, and type
Timepoint [15] 0 0
Up to 52 weeks
Secondary outcome [16] 0 0
Abnormal changes in EEG recordings compared to baseline with a focus on treatment-emergent epileptiform abnormalities
Timepoint [16] 0 0
Up to 52 weeks
Secondary outcome [17] 0 0
Systolic and diastolic blood pressure measurements
Timepoint [17] 0 0
Up to 52 weeks
Secondary outcome [18] 0 0
Heart rate measurements
Timepoint [18] 0 0
Up to 52 weeks
Secondary outcome [19] 0 0
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
Timepoint [19] 0 0
Up to 52 weeks
Secondary outcome [20] 0 0
Height in meters (m)
Timepoint [20] 0 0
Up to 52 weeks
Secondary outcome [21] 0 0
Weight in kilograms (kg)
Timepoint [21] 0 0
Up to 52 weeks
Secondary outcome [22] 0 0
Head circumference in centimeters (cm)
Timepoint [22] 0 0
Up to 52 weeks
Secondary outcome [23] 0 0
Tanner staging over time in participants aged 9 years and above
Timepoint [23] 0 0
Up to 52 weeks
Secondary outcome [24] 0 0
Plasma concentration of basmisanil
Timepoint [24] 0 0
Up to 52 weeks
Secondary outcome [25] 0 0
Plasma concentration of the basmisanil metabolite M1
Timepoint [25] 0 0
Up to 52 weeks
Secondary outcome [26] 0 0
Area under the concentration-time curve during one dosing interval at steady state (AUCtau,ss) of basmisanil
Timepoint [26] 0 0
Up to 52 weeks
Secondary outcome [27] 0 0
Maximum concentration at steady state (Cmax,ss) of basmisanil
Timepoint [27] 0 0
Up to 52 weeks
Secondary outcome [28] 0 0
Trough plasma concentration at steady state (Ctrough, ss) of basmisanil
Timepoint [28] 0 0
Up to 52 weeks
Secondary outcome [29] 0 0
Apparent clearance (CL/F) of basmisanil
Timepoint [29] 0 0
Up to 52 weeks
Secondary outcome [30] 0 0
Apparent volume of distribution (Vd/F) of basmisanil
Timepoint [30] 0 0
Up to 52 weeks
Secondary outcome [31] 0 0
Plasma concentration ratio of M1 to basmisanil at trough
Timepoint [31] 0 0
Up to 52 weeks
Secondary outcome [32] 0 0
Cmax,ss of M1
Timepoint [32] 0 0
Up to 52 weeks
Secondary outcome [33] 0 0
Ctrough, ss of M1
Timepoint [33] 0 0
Up to 52 weeks
Secondary outcome [34] 0 0
Quantitative EEG (qEEG) beta-band power
Timepoint [34] 0 0
Up to 52 weeks

Eligibility
Key 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
Minimum age
2 Years
Maximum age
14 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/03/2024
Sample size
Target
Accrual to date
Final
7
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Queensland Children?s Hospital - South Brisbane
Recruitment postcode(s) [1] 0 0
4101 - South Brisbane
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
North Carolina
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Poland
State/province [5] 0 0
Pozna?
Country [6] 0 0
Portugal
State/province [6] 0 0
Lisboa
Country [7] 0 0
Spain
State/province [7] 0 0
Barcelona
Country [8] 0 0
Spain
State/province [8] 0 0
Madrid
Country [9] 0 0
Spain
State/province [9] 0 0
Sevilla
Country [10] 0 0
United Kingdom
State/province [10] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05307679
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05307679