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

• Status: Active, not recruiting
• Trial end date: 2021-03-01
• Target enrollment: 0
• Participant gender: Male

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italfarmaco

Criteria

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