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

NCT ID: NCT06769633

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-02
• Study Completion Date: 2029-12-31

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).

Conditions

Duchenne Muscular Dystrophy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - from 4 to 6 years old

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

Group Type: EXPERIMENTAL

Givinostat Hydrochloride

Intervention Type: DRUG

Cohort 1 - from 4 to 6 years old

Cohort 2 - from 2 to 4 years old

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

Group Type: EXPERIMENTAL

Givinostat Hydrochloride - Cohort 2

Intervention Type: DRUG

Cohort 2 - from 2 to 4 years old

Interventions

Givinostat Hydrochloride

Cohort 1 - from 4 to 6 years old

Intervention Type: DRUG

Givinostat Hydrochloride - Cohort 2

Cohort 2 - from 2 to 4 years old

Intervention Type: DRUG

Other Intervention Names

Cohort 1; Cohort 2

Eligibility Criteria

Inclusion Criteria

1. Male children aged ≥2 to <6 years at screening (subjects ≥6 years of age at screening will not be enrolled into the study)

2. Written consent provided by parent/legal guardian and subject written assent, if applicable (according to local regulation)

3. A genetic diagnosis of DMD

4. Corticosteroid treatment considerations:

1. 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

2. For subjects without current corticosteroid treatment:

Must not start corticosteroids in the Core Phase of the study (ie, first 48 weeks).

1. Must have participated in the Core Phase study (48 weeks) and have attended the End of Treatment Visit

2. Give informed consent and /or assent in writing signed by the parent/legal guardian and/or subject (according to local regulation)

3. 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.

Exclusion Criteria

1. Exposure to another investigational drug within 3 months prior to the start of the study drug

2. Exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study drug

3. Received any gene therapy (eg, AAV Micro-dystrophin delivery) within 12 months prior to start of study drug

4. 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.

5. 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

6. 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

7. 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

8. 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)

9. 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

10. 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)

11. 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)

12. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening

13. 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)

14. 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

15. Hypersensitivity to any component of study drug

16. Sorbitol intolerance or malabsorption or have the hereditary form of fructose intolerance.

17. Body weight <10 kg at screening.

1. Platelet count, white blood cells, and/or haemoglobin <LLN at EOT/V12 (Note: for abnormal 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)

2. Current liver disease or impairment, including but not limited to an elevated total bilirubin (ie, >1.5 × ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert disease

3. 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)

4. Fasting triglycerides >300 mg/dL (3.42 mmol/L; 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 condition, the subject should be excluded)

5. Have presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results

6. Evidence of 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.

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 6 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Fortrea

INDUSTRY

Sponsor Role: collaborator

Italfarmaco

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Queen Fabiola Children's University Hospital HUDERF

Brussels, , Belgium

Site Status: RECRUITING

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

Milan, , Italy

Site Status: RECRUITING

Ospedale Pediatrico Bambino Gesù

Roma, , Italy

Site Status: RECRUITING

Policlinico Universitario Agostino Gemelli - Università Cattolica del Sacro Cuore

Roma, , Italy

Site Status: RECRUITING

Leids Universitair Medisch Centrum (LUMC)

Leiden, , Netherlands

Site Status: RECRUITING

Leeds Teaching Hospital NHS Trust

Leeds, England, United Kingdom

Site Status: NOT_YET_RECRUITING

Great Ormond Street Hospital - GOSH

London, England, United Kingdom

Site Status: NOT_YET_RECRUITING

Newcastle upon Tyne Hospitals NHS Foundation Trust - Newcastle University

Newcastle upon Tyne, England, United Kingdom

Site Status: RECRUITING

Oxford University Hospitals NHS Foundation Trust

Oxford, England, United Kingdom

Site Status: RECRUITING

Countries

Belgium; Italy; Netherlands; United Kingdom

Central Contacts

Italfarmaco Patient Advocacy

Role: CONTACT

patientadvocacy@italfarmacogroup.com

+39 02 64431

Italfarmaco Patient Advocacy

Role: CONTACT

patientadvocacy@italfarmacgroup.com

0264431

Facility Contacts

Nicolas Deconinck, MD

Role: primary

nicolas.deconink@hubruxelles.be

+32 2 4772945

Valeria Sansone, MD

Role: primary

valeria.sansone@centrocliniconemo.it

Adele D'Amico, MD

Role: primary

adele2.damico@opbg.net

+39 06 68592105

Eugenio Mercuri, MD

Role: primary

eugeniomaria.mercuri@policlinicogemelli.it

+39 06 30158576

Erik Niks, MD

Role: primary

duchenne@lumc.nl

Anne-Marie Childs, MD

Role: primary

anne-marie.childs@nhs.net

Mariacristina Scoto, MD

Role: primary

Mariacristina Scoto <Mariacristina.Scoto@gosh.nhs.uk>

Michela Guglieri, MD

Role: primary

Michela Guglieri <michela.guglieri@newcastle.ac.uk>

Laurent Servais, MD

Role: primary

Laurent Servais <laurent.servais@paediatrics.ox.ac.uk>

Other Identifiers

DSC/14/2357/52

Identifier Type: -

Identifier Source: org_study_id