Study in which all the patients take the same investigational drug with the aim of evaluate the long-term safety, tolerability, and efficacy of GIVINOSTAT in all the patients affected with Duchenne Muscolar Dystrophy who have been already treated in one of the GIVINOSTAT studies in the past
- Conditions
- Duchenne Muscular Dystrophy (DMD)MedDRA version: 20.0Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2017-000397-10-DE
- Lead Sponsor
- ITALFARMACO S.p.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Male
- Target Recruitment
- 222
Subjects must meet all the following 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:
o all the inclusion criteria and none of the exclusion criteria,
ohad 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,
onever 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 local regulations);
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:
oTrue 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.
oCondom with spermicide and the female partner must use an acceptable method of contraception, such as an oral, transdermal, injectable or implanted steroid-based contraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as for example cervical cap with spermicide jelly.
Are the trial subjects under 18? yes
Number of subjects for this age range: 214
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
Subjects presenting with any of the following criteria will not be included in the study:
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 (6. Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit* (for abnormal screening laboratory test results (>ULN), the triglycerides will be repeated once; if the repeat test result is still >ULN, 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 situations 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To assess the long term safety and tolerability of GIVINOSTAT in patients with DMD following core protocols program and with naïve GIVINOSTAT DMD subjects, i.e. subjects screened in study DSC/14/2357/48 who met:<br>- all the inclusion criteria and none of the exclusion criteria, <br>- never been randomized because the enrollment in the off-target group was completed.<br>;Secondary Objective: To evaluate the effects of long-term administration of GIVINOSTAT on muscular function and strength; <br>To evaluate the effects of long-term administration of GIVINOSTAT on respiratory function;<br>To evaluate the impact on daily activities and quality of life following long-term administration of GIVINOSTAT<br>;Primary end point(s): Type, incidence, and severity of treatment related/not related AEs and SAEs ;Timepoint(s) of evaluation of this end point: Baseline through week 48 and then at the end of the study
- Secondary Outcome Measures
Name Time Method