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

NCT06769633 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DSC/14/2357/52
• Study Type: interventional
• Target: 18
• Locations: 4 countries
• Sites: 9

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)

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne Muscular Dystrophy; Givinostat

Outcome Measures

Primary Outcomes (8)

• 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.

  Baseline up to week 48

• 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.

  Baseline up to week 48

• 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.

  Baseline up to week 48

• 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.

  Baseline up to week 48

• Core Phase: Cohort 2 - 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.

  Baseline up to week 48

• 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

  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.

  Baseline up to week 48

• 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 Outcomes (5)

• 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

Study Arms (2)

Cohort 1 - from 4 to 6 years old

EXPERIMENTAL

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

Drug: Givinostat Hydrochloride

Cohort 2 - from 2 to 4 years old

EXPERIMENTAL

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

Drug: Givinostat Hydrochloride - Cohort 2

Interventions

Givinostat Hydrochloride DRUG

Cohort 1 - from 4 to 6 years old

Also known as: Cohort 1

Cohort 1 - from 4 to 6 years old

Givinostat Hydrochloride - Cohort 2 DRUG

Cohort 2 - from 2 to 4 years old

Also known as: Cohort 2

Cohort 2 - from 2 to 4 years old

Eligibility Criteria

• Age: 2 Years - 6 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• Corticosteroid treatment considerations:
• For subject receiving a stable dose or oral systemic corticosteroids:
• No significant change in dose or dosing regimen (except for adjustments due to body weight change) for a minimum of 3 months immediately prior to the start of the study drug or
• For subjects without current corticosteroid treatment:
• Must not start corticosteroids in the Core Phase of the study (ie, first 48 weeks).
• Must have participated in the Core Phase study (48 weeks) and have attended the End of Treatment Visit
• Give informed consent and /or assent in writing signed by the parent/legal guardian and/or subject (according to local regulation)
• In stable oral systemic corticosteroids treatment with no significant change in dose or dosing regimen (except for adjustments due to body weight change). For subjects without corticosteroids during the Core Phase, the treatment can be started based on the Investigator's clinical medical judgement.

You may not qualify if:

• 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
• Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to the start of the study drug (eg, growth hormone). Note: Vitamin D, calcium, and any other supplements will be allowed.
• Have had surgery that might have an effect on muscle strength or function within 3 months prior to start of the study drug or planned surgery at any time during the study
• The presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect subject's safety, making it unlikely to complete the study or to be compliant with study-specific requirements that could impair the assessment of study results
• Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on Investigator clinical medical judgement
• Platelet count, white blood cells, and/or haemoglobin counts \< lower limit of normal (LLN) at screening (Note: for abnormal screening laboratory test results \[\<LLN\], the platelet count, white blood cell, and haemoglobin will be repeated once; if the repeat test result is still \<LLN, the subject will be excluded)
• Current or history of liver disease or impairment, including but not limited to a baseline elevated total bilirubin (ie, \>1.5 × upper limit of normal \[ULN\]), unless secondary to Gilbert disease or pattern consistent with Gilbert disease
• Inadequate renal function, as defined by serum Cystatin C result \>2 × ULN (Note: if the value is \>2 × ULN, the serum Cystatin C will be repeated once; if the repeated test result is still \>2 × ULN, the subject will be excluded)
• Fasting triglycerides \>300 mg/dL (3.42 mmol/L) at screening (Note: if the value is \>300 mg/dL, the triglycerides will be repeated once; if the repeated test result is still \>300 mg/dL in fasting, the subject should be excluded)
• Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
• Baseline corrected QT interval using Fridericia's formula (QTcF) \>450 msec (as the mean of 3 consecutive readings taken 5 minutes apart) or history of additional risk factors for torsades de pointes (ie, heart failure, hypokalaemia, or family history of long QT syndrome)
• Psychiatric illness or social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on the Investigator's clinical medical judgement
• Hypersensitivity to any component of study drug

Sponsors & Collaborators

• Italfarmaco: lead
• Fortrea: collaborator

Study Sites (9)

Queen Fabiola Children's University Hospital HUDERF

Brussels, 1020, Belgium

RECRUITING

Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca' Granda - NeuroMuscolar Omnicenter

Milan, 20162, Italy

RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

RECRUITING

Policlinico Universitario Agostino Gemelli - Università Cattolica del Sacro Cuore

Roma, 00165, Italy

RECRUITING

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2300 RC, Netherlands

RECRUITING

Leeds Teaching Hospital NHS Trust

Leeds, England, United Kingdom

NOT YET RECRUITING

Great Ormond Street Hospital - GOSH

London, England, United Kingdom

NOT YET RECRUITING

Newcastle upon Tyne Hospitals NHS Foundation Trust - Newcastle University

Newcastle upon Tyne, England, NE1 eBZ, United Kingdom

RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, England, OX3 9DU, United Kingdom

RECRUITING

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

givinostat hydrochloride; KPNA1 protein, human

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Italfarmaco Patient Advocacy

CONTACT

+39 02 64431; patientadvocacy@italfarmacogroup.com

Italfarmaco Patient Advocacy

CONTACT

0264431; patientadvocacy@italfarmacgroup.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2024
• First Posted: January 10, 2025
• Study Start: January 2, 2025
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1); NL (1); IT (3); GB (4)