Distrofia Muscolare di Becker (DMB) MedDRA version: 20.0 Level: PT Classification code 10059117 Term: Becker's muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: Givinostat (hydrochloride monohydrate)
Product Code: ITF2357
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Givinostat (hydrochloride monohydrate)
CAS Number: 732302-99-7
Curr
Sponsors
ITALFARMACO S.P.A.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Ambulant male patients aged =18 years to =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Exposure to another investigational drug within 3 months prior to the start of study treatment. 2. Use of any pharmacologic treatment, other than corticosteroids, that might have 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. 3. Surgery that might affect muscle strength or function within 3 months before study entry or planned surgery at any time during the study. 4. Presence of other clinically significant disease that in the Investigator’s opinion could adversely affect the safety of the patient, making it unlikely that the course of treatment or follow-up is completed, or could impair the assessment of study results. 5. A diagnosis of other uncontrolled neurological diseases or presence of relevant somatic disorders not related to BMD that may interfere with the ability to perform the muscle function tests and/or to comply with the study protocol procedures. 6. Platelet count, WBC count and hemoglobin at screening 1.5 x ULN), unless secondary to Gilbert’s disease or pattern consistent with Gilbert's disease. 9. Inadequate renal function, as defined by serum Cystatin C > 2 x the upper limit of normal (ULN). If the value is > 2 x ULN, serum Cystatin C will be repeated once, and if again > 2 x ULN becomes exclusionary. 10. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening. 11. Baseline corrected QT interval, Fredericia’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). 12. Current psychiatric illness/social situations rendering the potential patient unable to understand and comply with the muscle function tests and/or with the study protocol procedures. 13. Hypersensitivity to the components of study medication. 14. Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose intolerance. 15. Contraindications to muscle biopsy. 16. Contraindications to MRI/MRS (e.g., claustrophobia, metal implants, or seizure disorder). 17. Hypertriglyceridemia (> 1.5 x upper limit of normal [ULN])* * At screening, patients with hypertriglyceridemia can be enrolled if in stable treatment and with controlled levels of triglycerides (i.e. within normal range) for at least six months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish the histological effects of givinostat versus placebo administered over 12 months.;Secondary Objective: To establish the macroscopic muscle effects of givinostat versus placebo administered chronically over 12 months assessed by MRI/MRS. • To establish the other histological effects of givinostat versus placebo administered over 12 months. • To establish the efficacy of givinostat versus placebo administered chronically over 12 months in slowing disease progression. • To assess the safety and tolerability of givinostat versus placebo administered chronically. • To evaluate the pharmacokinetic (PK) profile of givinostat administered chronically in the target population. • To evaluate the impact of givinostat versus placebo administered chronically on quality of life and activities of daily living.;Primary end point(s): Mean change in mean Cross Sectional Area (CSA) comparing the histology of muscle biopsies ;Timepoint(s) of evaluation of this end point: Before and after 12 months of treatment with givinostat versus placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Mean change in fat fraction of vastus lateralis and soleus comparing Magnetic Resonance Spectroscopy (MRS); 2. Mean change in fat fraction of pelvic girdle and lower limb muscles comparing Magnetic Resonance Imaging (MRI); 3 .Mean CSA of pelvic girdle and lower limb muscles comparing MRI; 4. Mean change in other histology parameters (e.g. MFA%, % of total fibrosis, regenerative fibers) comparing the histology biopsies; 5. Mean change in Motor Function Measurement (MFM); 6. Mean change in Time Function Tests (time to climb four standard steps, time to rise from floor and time to walk/run 10 m); 7. Mean change in 6 Minute Walking Test (6MWT); 8. Proportion of patients with < 10% worsening in 6MWT; 9. Proportion of patients who lose the ability to rise from floor; 10. Proportion of patients who lose ambulation; 11. Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM); 12. Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36]);;Timepoint(s) of evaluation of this end point: 1. Before and after 12 months of treatment with givinostat versus placebo; 2. Before and after 12 months of treatment with givinostat versus placebo; 3. Before and after 12 months of treatment with givinostat versus placebo; 4. Before and after 12 months of treatment with givinostat; 5. Before and after 12 months of treatment with givinostat versus placebo; 6. Before and after 12 months of treatment with givinostat versus placebo; 7. Before and after 12 months of treatment with givinostat versus placebo; 8. At the end of study; 9. Baseline through end of study; 10. During the study; 11. Before and after 12 months of treatment with givinostat versus placebo; 12. Before and after 12 months of treatment with givinostat as compared to placebo; | — |
Countries
Italy, Netherlands
Contacts
Public ContactClinical Research and Development
ITALFARMACO S.P.A.
Outcome results
None listed