Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy
Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy
This is a phase 2, randomised, double-blind, placebo controlled study to evaluate the
 micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of
 givinostat in patients with Becker Muscular Dystrophy. Approximately 48 eligible patients
 will be randomized in a 2:1 ratio to be treated with givinostat or placebo for a period of 12
 months.
Givinostat or placebo oral suspension (10 mg/mL) will be administered orally as 2 oral doses
 daily while the subject is in fed state, according to the subject's weight.

 Study drug should be permanently stopped if any of the following occur:

 -  severe drug-related diarrhoea;

 -  any drug-related Serious Adverse Event (SAE);

 -  QTcorrected by Fridericia's formulas (QTcF) >500 msec;

 -  platelets (PLT) count ≤50 x 1.000.000.000/L (10E9/L);

 -  White blood cell (WBC) ≤ 2.0 x 10E9/L;

 -  Hemoglobin (Hb) ≤ 8.0 g/dL.

 Study drug should be temporarily stopped if any of the following occur:

 -  PLT count <75 x 10E9/L but >50 x 10E9/L;

 -  WBC < 3.0 x 10E9/L but > 2.0 x 10E9/L;

 -  Hb < 10.0 g/dL but > 8.0 g/dL;

 -  moderate or severe diarrhoea.

 -  tryglicerides >300 mg/dL In case the study drug was temporarily stopped, the study drug
 can be resumed at a level 20% smaller than the dose at which the Adverse Event leading
 to temporary stop occurred, once platelets and/or WBC and/or Hb and/or tryglicerides are
 normalized or when diarrhoea is mild
Inclusion Criteria:

 1. Ambulant patients with BMD diagnosis confirmed by genetic testing.

 2. Able and willing to give informed consent in writing.

 3. Able to perform 6MWT at screening with a minimum distance of 200 m and maximum
 distance of 450 m.

 4. If in treatment with systemic corticosteroids and/or angiotensin-converting-enzyme
 (ACE) inhibitor , and/or β or α adrenergic receptor blocker, no significant change in
 dosage or dosing regimen (excluding changes related to body weight change) for a
 minimum of 6 months immediately prior to start of study treatment.

 5. Patients must be willing to use adequate contraception. Contraceptive methods must be
 used from Randomization through 3 months after the last dose of study treatment.

 Exclusion Criteria:

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

 2. Use of any pharmacologic treatment, other than corticosteroids, that might have 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.

 3. Surgery that might affect muscle strength or function within 3 months before study
 entry or planned surgery at any time during the study.

 4. Presence of other clinically significant disease that in the Investigator's opinion
 could adversely affect the safety of the patient, making it unlikely that the course
 of treatment or follow-up is completed, or could impair the assessment of study
 results.

 5. A diagnosis of other neurological diseases or presence of relevant somatic disorders
 that are not related to BMD.

 6. Platelet count, WBC count and hemoglobin at screening < Lower Limit of Normal (LLN).
 If laboratory screening results are < LLN, platelet count, WBC count and hemoglobin
 are to be repeated once, and if again < LLN become exclusionary.

 7. Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or
 IV) or left ventricular ejection fraction < 50% at screening or with heart transplant.

 8. Current liver disease or impairment, including but not limited to elevated total
 bilirubin (> 1.5 x ULN), unless secondary to Gilbert's disease or pattern consistent
 with Gilbert's disease.

 9. Inadequate renal function, as defined by serum Cystatin C > 2 x the upper limit of
 normal (ULN). If the value is > 2 x ULN, serum Cystatin C will be repeated once, and
 if again > 2 x ULN becomes exclusionary.

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

 11. Baseline corrected QTcF > 450 msec, (as the mean of 3 consecutive readings 5 minutes
 apart) or history of additional risk factors for torsades de pointes (e.g., heart
 failure, hypokalemia, or family history of long QT syndrome).

 12. Current psychiatric illness/social situations rendering the potential patient unable
 to understand and comply with the muscle function tests and/or with the study protocol
 procedures.

 13. Hypersensitivity to the components of study medication.

 14. Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose
 intolerance.

 15. Contraindications to muscle biopsy.

 16. Contraindications to MRI/MRS (e.g., claustrophobia, metal implants, or seizure
 disorder).

 17. Hypertrygliceridemia (<1.5 per upper limit of normal)* * at screening, patient with
 hypertrygliceridemia can be enrolled if in stable treatment and with controlled level
 of tryglicerides (i.e. within normal range) for at least 6 months