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

Prior treatment

• CORE PHASE: Exposure to any other investigational drug within 3 months prior to the start of study drug
• CORE PHASE: Exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study drug
• CORE PHASE: Received any gene therapy (eg, Adeno-associated viruses Micro dystrophin delivery) within 12 months prior to the start of study drug
• CORE PHASE: 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 study drug (eg, growth hormone)
• CORE PHASE: Have had surgery that might have an effect on muscle strength or function within 3 months prior to the start of the study drug or planned surgery at any time during the study

Other illness

• EXTENSION PHASE: 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
• EXTENSION PHASE: 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
• CORE PHASE: 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
• CORE PHASE: Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on the Investigator's clinical medical judgement
• CORE PHASE: Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
• CORE PHASE: 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
• CORE PHASE: Hypersensitivity to any component of the study drug

Lab values

• EXTENSION PHASE: 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
• EXTENSION PHASE: Inadequate renal function, as defined by serum Cystatin C result >2 × ULN
• EXTENSION PHASE: Fasting triglycerides >300 mg/dL (3.42 mmol/L)
• CORE PHASE: 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)
• CORE PHASE: Platelet count, white blood cells, and/or haemoglobin < LLN at screening
• CORE PHASE: 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
• CORE PHASE: 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 condition, the subject should be excluded)
• CORE PHASE: Baseline QTcF >450 msec (as the mean of 3 consecutive readings taken 5 minutes ± 2 minutes apart) or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome)
• EXTENSION PHASE: Platelet count <150 × 109/L, white blood cells <3.0 × 109/L, and/or haemoglobin <10 mg/dL at EOT/V12

Other

• CORE PHASE: Body weight <9 kg at screening
• CORE PHASE: Sorbitol intolerance or malabsorption, or have the hereditary form of fructose intolerance

• CORE PHASE: Male children aged ≥2 to <6 years at screening (subjects ≥6 years of age at screening will not be enrolled into the study)
• CORE PHASE: Written consent provided by parent/legal guardian and subject written assent, if applicable (according to local regulation)
• CORE PHASE: A genetic diagnosis of DMD
• CORE PHASE: Corticosteroid treatment considerations: a. For subjects receiving a stable dose of 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 study drug or b. For subjects without current corticosteroids treatment: Must not start corticosteroids during core phase (ie, first 48 weeks)
• EXTENSION PHASE: Must have participated in the Core Phase study (48 weeks) and have attended the EOT/V12
• EXTENSION PHASE: Give informed consent and /or assent in writing signed by the parent/legal guardian and/or subject (according to local regulation)
• EXTENSION PHASE: 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.