Study to evaluate the efficacy and safety of givinostat in ambulant patients with Duchenne Muscular Dystrophy.
- Conditions
- Duchenne Muscular Dystrophy (DMD)MedDRA version: 19.1Level: PTClassification code 10013801Term: Duchenne muscular dystrophySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2016-000401-36-IT
- 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
- 192
1. Are ambulant males 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 of <10 seconds at screening;
7. Have manual muscle testing (MMT) of quadriceps at screening = Grade 3;
8. Are eligible according to the protocol-specified functional algorithm predictive of vastus lateralis muscle fat fraction (VL MFF) that should be in the range >10% but <30%;
9. Have used systemic corticosteroids for a minimum of 6 months immediately prior to the start of study treatment, with 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 and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
10. Subjects must be willing to use adequate contraception.
Contraceptive methods must be used from Randomization Visit 3 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-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: 192
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0
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;
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. Ankle joint contractures due to a fixed loss of =10 degrees of dorsiflexion from plantagrade assuming a normal range of dorsiflexion of 20 degree;
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 safetyof 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 neurological diseases or presence of relevant somatic disorders that are not related to DMD;
10. Have platelets count, White Blood Cell and Hemoglobin at screening 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; 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;
13. Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN). 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);
14. Have a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening;
15. Have a baseline corrected QT interval, Fridericia’s correction (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);
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 hypersensitivity to the components of study medication;
18. Have a sorbitol intolerance or sorbitol malabsorption, or have the hereditary form of fructose intolerance.
For the subgroup of subjects who will perform the magnetic resonance imaging (MRI) and spetroscopy (MRS) (i.e., MR Cohort):
19.Have contraindications to MRI or MRS (e.g., claustrophobia,
metal implants, or seizure disorder).
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To establish the effects of givinostat versus placebo administered chronically over 18 months to slow disease progression in ambulant DMD subjects;Secondary Objective: To assess the safety and tolerability of givinostat versus placebo administered chronically in DMD subjects.<br> To evaluate the pharmacokinetic (PK) profile of givinostat administered chronically in the target population.<br>To evaluate the impact on quality of life and activities of daily living of givinostat versus placebo administered chronically.<br><br>Exploratory objectives:<br>To evaluate the correlation between PK profile of givinostat and pharmacodynamics (PD) data.<br>To explore whether the effects of givinostat versus placebo administered chronically may be related to the type of DMD mutation or to the biomarkers.;Primary end point(s): Mean change in 4SC before and after 18 months of treatment of givinostat versus placebo.;Timepoint(s) of evaluation of this end point: 18 months
- Secondary Outcome Measures
Name Time Method