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Trial record 24 of 96 for:    Recruiting, Not yet recruiting, Available Studies | "Muscular Dystrophies"

Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy

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ClinicalTrials.gov Identifier: NCT03238235
Recruitment Status : Recruiting
First Posted : August 3, 2017
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
Italfarmaco

Brief 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.

Condition or disease Intervention/treatment Phase
Becker Muscular Dystrophy Drug: givinostat Drug: placebo Phase 2

Detailed 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. In case the study drug was temporarily stopped, the study drug can be resumed at a level 1/3 smaller than the one at which the Adverse Event leading to temporary stop occurred, once platelets, WBC or Hb are normalized or diarrhoea is mild (if treatment was stopped for moderate or severe diarrhoea).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 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 (BMD)
Actual Study Start Date : December 12, 2017
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2019


Arm Intervention/treatment
Active Comparator: givinostat
Givinostat oral suspension (10 mg/mL) twice daily in a fed state
Drug: givinostat
suspension of givinostat (10 mg/mL)
Other Name: Active Comparator: givinostat

Placebo Comparator: placebo
Placebo oral suspension (10 mg/mL) twice daily in a fed state
Drug: placebo
suspension manufactured to mimic givinostat
Other Name: Placebo Comparator: placebo




Primary Outcome Measures :
  1. Mean change in mean Cross Sectional Area (CSA) [ Time Frame: 12 months ]
    comparison of the histology of muscle biopsies before and after 12 months of treatment with givinostat versus placebo


Secondary Outcome Measures :
  1. Mean change in muscle fat fraction (MFF) of vastus lateralis [ Time Frame: 12 months ]
    Evaluation will be performed comparing Magnetic Resonance Spectroscopy (MRS) before and after 12 months of treatment with givinostat versus placebo.

  2. Mean change in MFF of thigh + pelvic girdle muscles [ Time Frame: 12 months ]
    Evaluation will be performed comparing Magnetic Resonance Imaging (MRI) before and after 12 months of treatment with givinostat versus placebo

  3. Mean CSA of thigh muscles [ Time Frame: 12 months ]
    Evaluation will be performed comparing MRI before and after 12 months of treatment with givinostat versus placebo

  4. Mean change in other histology parameters (e.g. Muscle Fibers Area Fraction [MFAF]%, % of total fibrosis, regenerative fibers) [ Time Frame: 12 months ]
    Evaluation will be performed comparing the histology biopsies before and after 12 months of treatment with givinostat

  5. Mean change in Motor Function Measurement (MFM) before and after 12 months of treatment with givinostat versus placebo [ Time Frame: 12 months ]
    Evaluation will be performed using the Motor Function Measurement scale

  6. Mean change in 6 Minute Walking Test (6MWT) before and after 12 months of treatment with givinostat versus placebo [ Time Frame: 12 months ]
  7. Proportion of patients with < 10% worsening in 6MWT at the end of study. [ Time Frame: 12 months ]
  8. Proportion of patients who lose the ability to rise from floor (Baseline through end of study). [ Time Frame: 12 months ]
  9. Proportion of patients who lose ambulation during the study [ Time Frame: 12 months ]
  10. Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM), before and after 12 months of treatment with givinostat versus placebo [ Time Frame: 12 months ]
  11. Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36]) before and after 12 months of treatment with givinostat as compared to placebo [ Time Frame: 12 months ]
  12. Number of patients experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) from Baseline through end of study (EOS). [ Time Frame: 12 months ]
  13. Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS). [ Time Frame: 12 months ]
  14. Changes from baseline to end of study of clinical laboratory tests [ Time Frame: 12 months ]
    number of participants with abnormal laboratory values

  15. Changes from baseline to end of study of vital signs [ Time Frame: 12 months ]
    number of participants with abnormal vital signs

  16. Changes from baseline to end of study of physical examination [ Time Frame: 12 months ]
    number of participants with abnormal physical examination assessments



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 β or α 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. 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03238235


Contacts
Contact: Reference Study ID Number: DSC/15/2357/53 + 39 02 6443 ext 2524 patientadvocacy@italfarmaco.com

Locations
Italy
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS Recruiting
Milan, Italy, 20122
Contact: Giacomo Comi, MD    + 39 6443 ext 2524    giacomo.comi@unimi.it   
Sponsors and Collaborators
Italfarmaco
Investigators
Principal Investigator: Giacomo Comi, MD Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS Milano, Italy, 20122

Responsible Party: Italfarmaco
ClinicalTrials.gov Identifier: NCT03238235     History of Changes
Other Study ID Numbers: DSC/15/2357/53
First Posted: August 3, 2017    Key Record Dates
Last Update Posted: May 4, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked