E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy (DMD) |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne Muscular Dystrophy (DMD) is A neuromuscular disease characterized by rapidly progressive muscle weakness and wasting
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the long term safety and tolerability of GIVINOSTAT oral suspension in patients with Duchenne Muscular Dystrophy (DMD) following core protocols program. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of long-term administration of GIVINOSTAT on muscular function and strength; To evaluate the effects of long-term administration of GIVINOSTAT on respiratory function; To evaluate the impact on daily activities and quality of life following long-term administration of GIVINOSTAT.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To clarify A.15 Answer: Male subjects affected by Duchenne Muscular Dystrophy previously enrolled in one of the other DMD GIVINOSTAT studies (e.g DSC/14/2357/43, DSC/14/2357/48 and DSC/14/2357/50), aged ≥7 years and 6 months
INCLUSION CRITERIA: 1. Must have participated in one of the previous studies with GIVINOSTAT in DMD and have attended the End of Study Visit; 2.Aged ≥7 years and 6 months 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: 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. 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.
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E.4 | Principal exclusion criteria |
Patients who meet any of the following criteria will NOT be eligible for enrolment into the trial:
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 (<LLN), the platelets count, White Blood Cell and Hemoglobin will be repeated once; if the repeat test result is still <LLN, then exclusionary); 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Type, incidence, and severity of treatment related/not related AEs and SAEs
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline through week 48 and then yearly till the end of the study
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E.5.2 | Secondary end point(s) |
Secondary endpoints
For ambulant patients: • Change from baseline in physical function as measured by 6MWT, NSAA, Time function tests (e.g. time to rise from floor, time to climb 4- stairs, time to 10m walk)(week 48 and then yearly till the end of the study) • Change from baseline in muscle strength (e.g. knee extension and elbow flexion) as measured by HHM (week 48 and then yearly till the end of the study) • Time to major disease milestones (e.g. time to loss of ambulation). For non-ambulant patients: • Change in physical function from baseline in the Egen Klassifikation (EK) score (week 48 and then yearly till the end of the study) • Change in patient and/or parent/caregiver reports of activities of daily living as measured by Barthel Index (week 48 and then yearly till the end of the study • Change in upper limbs muscle strength (week 48 and then yearly till the end of the study) evaluated by handheld myometry (HHM) For all patients: • Change from baseline in physical function as measured by the Performance of Upper Limb (PUL) and MFM (week 48 and then yearly till the end of the study) • Change from baseline in respiratory function (week 48 and then yearly till the end of the study) (e.g. FVC, FEV1, PEF) • Change in patient and/or parent/caregiver reports of quality of life as measured by PedsQL (week 48 and then yearly till the end of the study), • Time to major disease milestones (e.g. time to respiratory support needed during the day, time to scoliosis surgery, time to death). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 48 and then yearly till the end of the study, summary description can be found in study synopsis of protocol
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.1.7.1 | Other trial design description |
This is an open label, long-term safety, tolerability, and efficacy study of GIVINOSTAT |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
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E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Germany |
Italy |
Netherlands |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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LVLS. The end of the trial is defined as the date of the last visit of the last subject undergoing the trial. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |