Patient case (clinical description): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient's own account: I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Clinical trial: Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy

Eligibility criteria:
Inclusion Criteria:

          1. Are an ambulant male aged ≥6 years at randomisation with DMD characteristic clinical
             symptoms or signs (e.g., proximal muscle weakness, Gowers' maneuver, elevated serum
             creatinine kinase level) already present at screening;

          2. Have DMD diagnosis confirmed by genetic testing;

          3. Are able to give informed assent and/or consent in writing signed by the subject
             and/or parent/legal guardian (according to local regulations);

          4. Are able to complete 2 Four Stairs Climb test (4SC) screening assessments; the results
             of these tests must be within ±1 second of each other;

          5. Have the mean of 2 screening 4SC assessments ≤8 seconds;

          6. Have time to rise from floor between ≥3 and <10 seconds at screening

          7. Have manual muscle testing (MMT) of quadriceps at screening Grade ≥- 3;

          8. Have used systemic corticosteroids for a minimum of 6 months immediately prior to the
             start of study treatment, with no significant change in corticosteroids type or dosage
             or dosing regimen (excluding changes related to body weight change) for a minimum of 6
             months immediately prior to start of study treatment and a reasonable expectation that
             dosage and dosing regimen will not change significantly for the duration of the study.

          9. Subjects must be willing to use adequate contraception.

        Exclusion Criteria:

          1. Have exposure to another investigational drug within 3 months prior to the start of
             study treatment;

          2. Have exposure to idebenone within 3 months prior to the start of study treatment;

          3. Have exposure to any dystrophin restoration product (e.g., Ataluren, Exon skipping)
             within 6 months prior to the start of study treatment;

          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 study
             treatment (e.g., growth hormone); Vitamin D, calcium, and any other supplements will
             be allowed as long as their intake has been stable for 3 months prior to the start of
             study treatment; Testosterone will also be allowed if it is used as a replacement
             therapy for the treatment of delayed puberty, and testosterone dose and regimen have
             been stable for at least 6 months and circulating testosterone levels are within the
             normal ranges for the subject's age;

          5. Have surgery that might have an effect on muscle strength or function within 3 months
             before study entry or planned surgery at any time during the study;

          6. Loss of ≥30 degrees of plantar flexion from the normal range of movement at the ankle
             joint due to contracture (i.e. fixed loss of more than 10 degrees of plantar flexion
             from plantigrade, assuming normal range of dorsiflexion of 20 degrees;

          7. Change in contracture treatment such as serial casting, contracture control devices,
             night splints, stretching exercises (passive, active, self) within 3 months prior to
             enrollment, or expected need for such intervention during the study;

          8. 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;

          9. Have a diagnosis of other uncontrolled neurological diseases or presence of relevant
             uncontrolled somatic disorders that are not related to DMD;

         10. Have platelets count at screening < Lower Limit of Normal (LLN);

         11. Have symptomatic cardiomyopathy or heart failure (New York Heart Association Class III
             or IV) or left ventricular ejection fraction <50% at screening;

         12. Have a current or history of liver disease or impairment;

         13. Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of
             normal (ULN);

         14. Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit;

         15. Have a baseline QTcF >450 msec, or history of additional risk factors for torsades de
             pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome);

         16. Have a psychiatric illness/social situations rendering the potential subject unable to
             understand and comply with the muscle function tests and/or with the study protocol
             procedures;

         17. Have any known allergic reaction to givinostat or any of its excipients.

         18. Have any hypersensitivity to the components of study medication;

         19. Have a sorbitol intolerance or sorbitol malabsorption, or have the hereditary form of
             fructose intolerance.

         20. Have contraindications to MRI or MRS (e.g., claustrophobia, metal implants, or seizure
             disorder).

        At the discretion of the Investigator, subjects not meeting inclusion/exclusion criteria
        may be re-screened twice with an interval of at least 3 months between assessments.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 6 Years old.
Subject must be at most 17 Years

Eligibility (NLI label): Entailment