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Trial record 1 of 4 for:    basmisanil
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A Study to Evaluate the Safety and Efficacy of Basmisanil Treatment in Children Aged 2-14 Years With Dup15q Syndrome

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ClinicalTrials.gov Identifier: NCT05307679
Recruitment Status : Terminated (The study was terminated due to slow recruitment and was not related to safety or tolerability.)
First Posted : April 1, 2022
Last Update Posted : May 16, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

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.

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 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 Participants Aged 2 to 14 Years Old With Dup15q Syndrome Followed by a 2-Year Optional Open-Label Extension
Actual Study Start Date : December 16, 2022
Actual Primary Completion Date : March 4, 2024
Actual Study Completion Date : March 4, 2024

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Vineland-3 adaptive behavior composite scores [ Time Frame: Up to 52 weeks ]

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


Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 14 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05307679


Locations
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United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90010
Rady Children's Hospital - San Diego
San Diego, California, United States, 92123
United States, Illinois
Rush University Medical Center
Chicago, Illinois, United States, 60612-3244
United States, North Carolina
University of North Carolina At Chapel Hill
Chapel Hill, North Carolina, United States, 27514
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37212
Poland
Uniwersytecki Szpital Kliniczny w Poznaniu; Od. Kliniczny Neurologii Dzieci i M?odziezy
Pozna?, Poland, 60-355
Portugal
CHULC, E.P.E. - Hospital Dona Estefania; Servico de Neuropediatria
Lisboa, Portugal, 1169-045
Spain
Hospital Sant Joan De Deu
Esplugues De Llobregas, Barcelona, Spain, 08950
Hospital Universitario La Paz; Servicio de Neurologia
Madrid, Spain, 28046
Hospital Universitario Virgen del Rocío
Sevilla, Spain, 41013
United Kingdom
Evelina London Children's Hospital
London, United Kingdom, SE1 7EH
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Additional Information:
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05307679    
Other Study ID Numbers: BP42992
First Posted: April 1, 2022    Key Record Dates
Last Update Posted: May 16, 2024
Last Verified: May 2024
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).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
dup15q
dup15q syndrome
15q
duplication 15q
15q duplication
chromosome 15q duplication
15q duplication syndrome
duplication 15
triplication 15
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes