Givinostat in Duchenne's Muscular Dystrophy Long-term Safety and Tolerability Study

• Status: Enrolling by invitation
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: Male

Summary

This is an open label, long-term safety, tolerability, and efficacy study of GIVINOSTAT in all DMD (Duchenne's muscular dystrophy) patients who have been previously treated in one of the GIVINOSTAT studies.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italfarmaco
• Collaborator: Cromsource

Criteria

Inclusion Criteria:

1. Must have participated in one of the previous studies with GIVINOSTAT in DMD and have attended the End of Study Visit or must have been screened in study DSC/14/2357/48 and met:

• all the inclusion criteria and none of the exclusion criteria,

• had a baseline vastus lateralis muscle fat fraction (VL MFF) assessed by MRS in the range ≤5% or >30%, i.e. included in"off-target" group,

• never been randomized because, the enrollment in the off target group was completed.

2. Aged ≥6 years old;

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

4. Subjects must be willing to use adequate contraception:

• Contraceptive methods must since the previous GIVINOSTAT study through 3 months after the last dose of study drug, and include the following:

• True abstinence (absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the subject.

• Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.

• Condom with spermicide and the female partner must use an acceptable method of contraception, such as an oral,

• transdermal, injectable or implanted steroid-basedcontraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such asfor example cervical cap with spermicide jelly.

Exclusion Criteria:

1. Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to be enrolled in this study (e.g., growth hormone); Vitamin D, calcium, and any other supplements will be allowed;

2. Use of any current investigational drug other than Givinostat;

3. 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;

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

5. Have platelets count, White Blood Cell and Hemoglobin at screening < Lower Limit of Normal (LLN)* (for abnormal screening laboratory test results (count, White Blood Cell and Hemoglobin will be repeated once; if the repeat test result is still

6. Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit* (for abnormal screening laboratory test results (>300 mg/dL), the triglycerides will be repeated once; if the repeat test result is still >300 mg/dL, then exclusionary);

7. Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN) at screening visit*. If the value is >2 x ULN, the serum Cystatin C will be repeated once; if the repeated test result is still >2 x ULN, the subject should be excluded);

8. Have heart failure (New York Heart Association Class III or IV)

9. Have a current liver disease or impairment, including but not limited to an elevated total bilirubin* (i.e. > 1.5 x ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert's;

10. Have a baseline 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);

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

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

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

• the Investigators to evaluate these exclusion criteria can use the laboratory results obtained within 5 months from V1, to allow the continuity of the treatment. It is worth noting, as soon as the site will receive the laboratory results done in screening/baseline (Visit 1) visit they will check the GIVINOSTAT dose and modify it as per protocol safety rules and/or dosage modifications rules.