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

• Status: Active, not recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: Male

Summary

it is a randomised, double blind, parallel group, placebo controlled study. A total of 179 male ambulant subjects will be randomised 2:1 (givinostat:placebo).

Subjects will be stratified for their concomitant use of steroids in 4 strata:

1. Deflazacort daily regimen

2. Deflazacort intermittent regimen

3. Other steroids daily regimen

4. Other steroids intermittent regimen. The study duration is planned for 19 months.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italfarmaco
• Collaborators: inVentiv Health Clinical; Syneos Health

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.