This is a Phase 2 Open-label (Core Phase Plus Extension Phase) With 2 Cohorts Study to Assess the Pharmacokinetics and Safety of Givinostat in younger DMD Patients.
* Planned screening duration: approximately 4 weeks * Planned Core Treatment duration: approximately 48 weeks * Planned Extension Treatment duration: approximately 96 weeks * Planned Follow Up duration: approximately 4 weeks (± 7 days) * Total duration of study participation: up to 151 weeks (ie, 37-38 months)
Male children aged ≥2 to <6 years at screening (subjects ≥6 years of age at screening will not be enrolled into the study)
Written consent provided by parent/legal guardian and subject written assent, if applicable (according to local regulation)
A genetic diagnosis of DMD
Must have participated in the Core Phase study (48 weeks) and have attended the End of Treatment Visit
Core Phase
Exposure to another investigational drug within 3 months prior to the start of the study drug
Exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study drug
Received any gene therapy (eg, AAV Micro-dystrophin delivery) within 12 months prior to start of study drug
Sequential
Givinostat Hydrochloride
DrugCohort 1 - from 4 to 6 years old
Givinostat Hydrochloride - Cohort 2
DrugCohort 2 - from 2 to 4 years old
Core Phase: Cohort 1 - Change from baseline of the pharmacokinetic (PK) parameter Area under the concentration-time curve from dosing (time 0) to time t at steady state (AUC0-T,ss).
Pharmacokinetic samples will be collected 1 pre-dose in the morning and 3 post-dose (0-2 h, 4-6 h, 6-8 h) after 1 week (Visit 3) and after 6 months (Visit 10). Sampling times will be randomly assigned to each subject to collect at least 1 pre-dose sample and 2 post-dose samples in each subject. At these timepoints, the subject will be asked to take the morning dose at the site. Samples collected after 1 week of treatment will be used for the exploratory PK analysis.
Core Phase: Cohort 1 - Change from baseline of the pharmacokinetic (PK) parameter maximum plasma concentration at steady state (Cmax,ss).
Pharmacokinetic samples will be collected 1 pre-dose in the morning and 3 post-dose (0-2 h, 4-6 h, 6-8 h) after 1 week (Visit 3) and after 6 months (Visit 10). Sampling times will be randomly assigned to each subject to collect at least 1 pre-dose sample and 2 post-dose samples in each subject. At these timepoints, the subject will be asked to take the morning dose at the site. Samples collected after 1 week of treatment will be used for the exploratory PK analysis.
Core Phase: Cohort 1 - Change from baseline of the pharmacokinetic (PK) parameter elimination half-life (t1/2) assessed after at least 7 days of dosing.
Pharmacokinetic samples will be collected 1 pre-dose in the morning and 3 post-dose (0-2 h, 4-6 h, 6-8 h) after 1 week (Visit 3) and after 6 months (Visit 10). Sampling times will be randomly assigned to each subject to collect at least 1 pre-dose sample and 2 post-dose samples in each subject. At these timepoints, the subject will be asked to take the morning dose at the site. Samples collected after 1 week of treatment will be used for the exploratory PK analysis.
Core Phase: Cohort 2 - Change from baseline of the pharmacokinetic (PK) parameter Area under the concentration-time curve from dosing (time 0) to time t at steady state (AUC0-T,ss).
Pharmacokinetic samples will be collected 1 pre-dose in the morning and 3 post-dose (0-2 h, 4-6 h, 6-8 h) after 1 week (Visit 3) and after 6 months (Visit 10). Sampling times will be randomly assigned to each subject to collect at least 1 pre-dose sample and 2 post-dose samples in each subject. At these timepoints, the subject will be asked to take the morning dose at the site. Samples collected after 1 week of treatment will be used for the exploratory PK analysis.
Core Phase: Type, incidence, and severity of treatment-emergent adverse events
Core Phase: Proportion of patients experiencing treatment-emergent adverse events
Core Phase: Change from baseline as measured by North Star Ambulatory Assessment (NSAA) in cohort 1 after 48 weeks of treatment of givinostat.
Core Phase: Change from baseline as measured by Bayley III Gross Motor in cohort 2 after 48 weeks of treatment of givinostat.
Click on the lead sponsor to view all of their trials.
Italfarmaco
Lead sponsor
Fortrea
Collaborator
