Pharmacokinetics and Safety of Givinostat in DMD Patients Ages From at Least 2 Years to Less Then 6 Years Old

Phase 2

Recruiting

• Conditions: Duchenne Muscular Dystrophy
• Interventions: Drug: Givinostat Hydrochloride - Cohort 2; Drug: Givinostat Hydrochloride

• Registration Number: NCT06769633
• Lead Sponsor: Italfarmaco

Brief Summary

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)

Detailed Description

This is an open-label, multicentre, multicountry, 2 cohorts study to evaluate the PK profile and safety of givinostat in subjects with DMD aged ≥4 to \<6 years for Cohort 1 and aged ≥2 to \<4 years for Cohort 2. The starting dose for Cohort 2 will be confirmed/adjusted with results of the interim analysis of Cohort 1. The study will consist of 2 phases, a Core Phase and an Extension Phase. Two final analyses will be conducted, the first at the end of the Core Phase and the second at the end of the Extension Phase (core and extension data will be combined).

The study will enrol approximately 18 subjects (approximately 9 subjects \[aged ≥4 to \<6 years\] in Cohort 1 and approximately 9 subjects \[aged ≥2 to \<4 years\] in Cohort 2).

Study Timeline

• Study First Submitted: 2024-12-11
• Status Verified: 2025-01
• Study Start: 2025-01-02
• Study First Submitted QC: 2025-01-07
• Study First Posted: 2025-01-10
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-24
• Primary Completion: 2029-12
• Study Completion: 2029-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 18

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2 - from 2 to 4 years old	Givinostat Hydrochloride - Cohort 2	Drug: Givinostat Givinostat has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose will be confirmed/adjusted with results of the interim analysis of cohort 1. Other Names: - ITF2357
Cohort 1 - from 4 to 6 years old	Givinostat Hydrochloride	Drug: Givinostat Givinostat has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose could be reduced based on predefined safety rules. Other Names: - ITF2357

Primary Outcome Measures

Name	Time	Method
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).	Baseline up to week 48	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).	Baseline up to week 48	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.	Baseline up to week 48	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).	Baseline up to week 48	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 maximum plasma concentration at steady state (Cmax,ss).	Baseline up to week 48	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 elimination half-life (t1/2) assessed after at least 7 days of dosing	Baseline up to week 48	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.
Extension Phase: Type, incidence, and severity of treatment-emergent adverse events	postbaseline up to Week 144
Extension Phase: Proportion of patients experiencing treatment-emergent adverse events	postbaseline up to Week 144

Secondary Outcome Measures

Name	Time	Method
Core Phase: Type, incidence, and severity of treatment-emergent adverse events	Baseline up to week 48
Core Phase: Proportion of patients experiencing treatment-emergent adverse events	Baseline up to week 48
Core Phase: Change from baseline as measured by North Star Ambulatory Assessment (NSAA) in cohort 1 after 48 weeks of treatment of givinostat.	Baseline up to week 48
Core Phase: Change from baseline as measured by Bayley III Gross Motor in cohort 2 after 48 weeks of treatment of givinostat.	Baseline up to week 48
Core Phase: Change from baseline in quality of life (as measured by health-related quality of life, HRQOL) at week 48 of treatment of givinostat	Baseline up to week 48

Trial Locations

Locations (9)

Queen Fabiola Children's University Hospital HUDERF; 🇧🇪 Bruxelles, Belgium

Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca' Granda - NeuroMuscolar Omnicenter; 🇮🇹 Milano, Italy

Ospedale Pediatrico Bambino Gesù; 🇮🇹 Roma, Italy

Policlinico Universitario Agostino Gemelli - Università Cattolica del Sacro Cuore; 🇮🇹 Roma, Italy

Leids Universitair Medisch Centrum (LUMC); 🇳🇱 Leiden, Netherlands

Leeds Teaching Hospital NHS Trust; 🇬🇧 Leeds, England, United Kingdom

Great Ormond Street Hospital - GOSH; 🇬🇧 London, England, United Kingdom

Newcastle upon Tyne Hospitals NHS Foundation Trust - Newcastle University; 🇬🇧 Newcastle Upon Tyne, England, United Kingdom

Oxford University Hospitals NHS Foundation Trust; 🇬🇧 Oxford, England, United Kingdom