Evaluating Givinostat for Young Children with Duchenne Muscular Dystrophy

A Phase 2 Open-label (Core Phase Plus Extension Phase) With 2 Cohorts Study to Assess the Pharmacokinetics and Safety of Givinostat in DMD Patients Ages From at Least 2 Years to Less Than 6 Years Old

This study is testing a new drug called Givinostat to see if it's safe and how it works in young children aged 2 to 6 with Duchenne Muscular Dystrophy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 2 Years to 6 Years
• Sex: Male
• Sponsor: Italfarmaco (industry)
• Locations: 9 sites (Brussels and 8 other locations)
• Trial ID: NCT06769633 on ClinicalTrials.gov

What this trial studies

This Phase 2 open-label study aims to assess the pharmacokinetics and safety of Givinostat in young patients with Duchenne Muscular Dystrophy (DMD) aged between 2 and 6 years. The study consists of two cohorts, with one group for children aged 2 to less than 4 years and another for those aged 4 to less than 6 years. Participants will undergo a core treatment phase lasting approximately 48 weeks, followed by an extension phase of about 96 weeks, with a total study duration of up to 151 weeks. The study will evaluate the drug's safety and how it is processed in the body, with a planned enrollment of around 18 subjects.

Who should consider this trial

Good fit: Ideal candidates for this study are male children aged 2 to less than 6 years with a genetic diagnosis of Duchenne Muscular Dystrophy.

Not a fit: Patients who are older than 6 years or those who do not have a genetic diagnosis of DMD will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option that may improve the management of Duchenne Muscular Dystrophy in young children.

How similar studies have performed: Other studies have shown promise in evaluating treatments for Duchenne Muscular Dystrophy, but this specific approach with Givinostat in this age group is relatively novel.

Eligibility criteria

Inclusion Criteria - Core Phase:

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).

Inclusion Criteria - Extension Phase:

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 - Core Phase

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.

Exclusion Criteria - Extension Phase

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.

Where this trial is running

Brussels and 8 other locations

• Queen Fabiola Children's University Hospital HUDERF — Brussels, Belgium (RECRUITING)
• Fondazione Serena Onlus - Azienda Ospedaliera Niguarda Ca' Granda - NeuroMuscolar Omnicenter — Milan, Italy (RECRUITING)
• Ospedale Pediatrico Bambino Gesù — Roma, Italy (RECRUITING)
• Policlinico Universitario Agostino Gemelli - Università Cattolica del Sacro Cuore — Roma, Italy (RECRUITING)
• Leids Universitair Medisch Centrum (LUMC) — Leiden, 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, United Kingdom (RECRUITING)
• Oxford University Hospitals NHS Foundation Trust — Oxford, England, United Kingdom (RECRUITING)

Study contacts

• Study coordinator: Italfarmaco Patient Advocacy

Conditions: Duchenne Muscular Dystrophy, Givinostat