Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy

Ki vehet részt

• Patients must satisfy all the following criteria:
• Children and adolescent males aged ≥ 9 to <18 years at screening (patients ≥ 18 years of age at screening will not be enrolled into the study)
• Are able to give informed assent and/or consent in writing signed by the patient and/or parent/legal guardian (according to local regulations)
• A genetic diagnosis of DMD
• Non-ambulant, defined as being wheelchair bound and:; Unable to perform the 10-meter walk/run test (10MWT), or; Unable to complete the 10MWT in 30 seconds or less, without any support or devices
• Performance of the Upper Limb test (PUL version 2.0) entry item scores 3 to 6
• If on medication for DMD-associated cardiomyopathy (eg, ACE inhibitor, β-blocker, diuretics), stable for ≥1 month immediately prior to start of study treatment, if any
• Stable corticosteroids, defined as:; Receiving systemic corticosteroids for a minimum of 6 months immediately prior to start of study treatment; No significant change in dose or dosing regimen (except for adjustments due to body weight change) for a minimum of 6 months immediately prior to start of study treatment
• Willing to use adequate contraception. Effective contraceptive methods must be used from randomisation visit through 3 months after the last dose of study drug, and include the following:; True abstinence (ie, absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, post-ovulation, and symptothermal methods) and withdrawal are not acceptable methods of contraception; Condom with spermicide and the female partner must use an effective method of contraception, such as an oral, transdermal, injectable or implanted hormonal contraceptive; intrauterine device; bilateral tubal occlusion, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as for example cervical cap with spermicide jelly

Ki nem vehet részt

• Exposure to another investigational drug within 3 months prior to start of study treatment
• Have exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study treatment
• Having received any gene therapy (eg, AAV Micro-dystrophin delivery) prior to start of study treatment
• Use of testosterone, unless used as a replacement therapy for the treatment of delayed puberty. The testosterone dose and regimen should be stable within 6 months prior to the start of study treatment, and circulating testosterone levels should be within the normal ranges for the patient's age
• Requirement for daytime ventilator assistance (Note: Night ventilator assistance and use of bi-level positive airway pressure therapy is allowed)
• Episode of respiratory failure within the 8 weeks prior to screening
• Major surgical procedure (including scoliosis surgery) planned within 1 year of the start of study treatment
• Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, emphysema, recurrent pneumonia that in the opinion of the Investigator might impact respiratory function
• Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
• Hypersensitivity to any component of study medication
• Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on Investigator judgement
• Psychiatric illness or social situations rendering the potential patient unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on Investigator judgement
• Have contraindications to MRI scan (eg, claustrophobia, metal implants, or uncontrolled seizure disorder), based on Investigator's judgement
• Use of any pharmacologic treatment or supplement (other than corticosteroids), that might have had an effect on muscle strength or function within 3 months prior to the start of study treatment (eg, growth hormone); vitamin D, calcium and any other supplements will be allowed
• Symptomatic cardiomyopathy or heart failure and/or left ventricular ejection fraction <45%
• Baseline corrected QT interval using Fredericia's formula (QTcF) >450 msec (as the mean of 3 consecutive readings 5 minutes apart) or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome)
• Platelets, white blood cells, and/or haemoglobin < lower limit of normal (LLN) at screening (Note: for abnormal screening laboratory test results [<LLN], the platelets count, white blood cell, and haemoglobin will be repeated once; if the repeat test result is still <LLN, the patient should 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, the patient should 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 patient should be excluded)
• Patients will be excluded from the study if they satisfy any of the following criteria:
• Elbow-flexion contractures >30° in the dominant arm
• Inability to perform consistent PUL 2.0 measurement within ±2 points without shoulder domain or within ±3 points with shoulder domain during paired testing at screening
• Forced Vital Capacity % of predicted <40%
• Sorbitol intolerance or malabsorption, or have the hereditary form of fructose intolerance