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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03238235
Other study ID # DSC/15/2357/53
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date December 12, 2017
Est. completion date March 19, 2021

Study information

Verified date January 2022
Source Italfarmaco
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a phase 2, randomised, double-blind, placebo controlled study to evaluate the micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of givinostat in patients with Becker Muscular Dystrophy. Approximately 48 eligible patients will be randomized in a 2:1 ratio to be treated with givinostat or placebo for a period of 12 months.


Description:

Givinostat or placebo oral suspension (10 mg/mL) will be administered orally as 2 oral doses daily while the subject is in fed state, according to the subject's weight. Study drug should be permanently stopped if any of the following occur: - severe drug-related diarrhoea; - any drug-related Serious Adverse Event (SAE); - QTcorrected by Fridericia's formulas (QTcF) >500 msec; - platelets (PLT) count ≤50 x 1.000.000.000/L (10E9/L); - White blood cell (WBC) ≤ 2.0 x 10E9/L; - Hemoglobin (Hb) ≤ 8.0 g/dL. Study drug should be temporarily stopped if any of the following occur: - PLT count <75 x 10E9/L but >50 x 10E9/L; - WBC < 3.0 x 10E9/L but > 2.0 x 10E9/L; - Hb < 10.0 g/dL but > 8.0 g/dL; - moderate or severe diarrhoea. - tryglicerides >300 mg/dL In case the study drug was temporarily stopped, the study drug can be resumed at a level 20% smaller than the dose at which the Adverse Event leading to temporary stop occurred, once platelets and/or WBC and/or Hb and/or tryglicerides are normalized or when diarrhoea is mild


Recruitment information / eligibility

Status Completed
Enrollment 51
Est. completion date March 19, 2021
Est. primary completion date March 19, 2021
Accepts healthy volunteers No
Gender Male
Age group 18 Years to 65 Years
Eligibility Inclusion Criteria: 1. Ambulant patients with BMD diagnosis confirmed by genetic testing. 2. Able and willing to give informed consent in writing. 3. Able to perform 6MWT at screening with a minimum distance of 200 m and maximum distance of 450 m. 4. If in treatment with systemic corticosteroids and/or angiotensin-converting-enzyme (ACE) inhibitor , and/or ß or a adrenergic receptor blocker, 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. 5. Patients must be willing to use adequate contraception. Contraceptive methods must be used from Randomization through 3 months after the last dose of study treatment. 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 neurological diseases or presence of relevant somatic disorders that are not related to BMD. 6. Platelet count, WBC count and hemoglobin at screening < Lower Limit of Normal (LLN). If laboratory screening results are < LLN, platelet count, WBC count and hemoglobin are to be repeated once, and if again < LLN become exclusionary. 7. Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction < 50% at screening or with heart transplant. 8. Current liver disease or impairment, including but not limited to elevated total bilirubin (> 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 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. Hypertrygliceridemia (<1.5 per upper limit of normal)* * at screening, patient with hypertrygliceridemia can be enrolled if in stable treatment and with controlled level of tryglicerides (i.e. within normal range) for at least 6 months

Study Design


Intervention

Drug:
givinostat
suspension of givinostat (10 mg/mL)
placebo
suspension manufactured to mimic givinostat

Locations

Country Name City State
Italy Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS Milan
Netherlands Leiden University Medical Center LUMC Leiden

Sponsors (1)

Lead Sponsor Collaborator
Italfarmaco

Countries where clinical trial is conducted

Italy,  Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Primary Mean change in total fibrosis (%) Mean change in total fibrosis (%) comparing the histology of muscle biopsies before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Mean change in fat fraction of vastus lateralis and soleus Evaluation will be performed comparing Magnetic Resonance Spectroscopy (MRS) before and after 12 months of treatment with givinostat versus placebo. 12 months
Secondary Mean change in fat fraction of pelvic girdle and lower limb muscles Evaluation will be performed comparing Magnetic Resonance Imaging (MRI) before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Mean CSA of pelvic girdle and lower limb muscles Evaluation will be performed comparing MRI before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Mean change in other histology parameters (e.g. Muscle Fibers Area Fraction [MFAF]%, % of total fibrosis, regenerative fibers) Evaluation will be performed comparing the histology biopsies before and after 12 months of treatment with givinostat 12 months
Secondary Mean change in Motor Function Measurement (MFM) Evaluation will be performed using the Motor Function Measurement scale before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Mean change in 6 Minute Walking Test (6MWT) Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Proportion of patients with < 10% worsening in 6MWT at the end of study. Proportion of patients with < 10% worsening in 6MWT at the end of study. 12 months
Secondary Proportion of patients who lose the ability to rise from floor (Baseline through end of study). Proportion of patients who lose the ability to rise from floor (Baseline through 12 months
Secondary Proportion of patients who lose ambulation during the study Proportion of patients who lose ambulation during the study 12 months
Secondary Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM), Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo 12 months
Secondary Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36]) Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo 12 months
Secondary Number of patients experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) from Baseline through end of study (EOS). Number of patients experiencing treatment-emergent adverse events (TEAEs) 12 months
Secondary Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS). Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS). 12 months
Secondary Changes from baseline to end of study of vital sign and clinical laboratory tests number of participants with abnormal laboratory values 12 months
Secondary Changes from baseline to end of study of physical examination number of participants with abnormal physical examination assessments 12 months
Secondary Mean change in Time Function Test Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo 12 months
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