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Trial record 9 of 1004 for:    BMD

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 : August 30, 2019
Sponsor:
Information provided by (Responsible Party):
Italfarmaco

Tracking Information
First Submitted Date  ICMJE July 12, 2017
First Posted Date  ICMJE August 3, 2017
Last Update Posted Date August 30, 2019
Actual Study Start Date  ICMJE December 12, 2017
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 28, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
Mean change in mean Cross Sectional Area (CSA) [ Time Frame: 12 months ]
Comparision of the histology of muscle biopsies before and after 12 months of treatment with givinostat versus placebo
Change History Complete list of historical versions of study NCT03238235 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Mean change in muscle fat fraction (MFF) of vastus lateralis and soleus [ Time Frame: 12 months ]
    Evaluation will be performed comparing Magnetic Resonance Spectroscopy (MRS) before and after 12 months of treatment with givinostat versus placebo.
  • Mean change in fat fraction of pelvic girdle and lower limb 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
  • Mean CSA of pelvic girdle and lower limb muscles [ Time Frame: 12 months ]
    Evaluation will be performed comparing MRI before and after 12 months of treatment with givinostat versus placebo
  • 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
  • Mean change in Motor Function Measurement (MFM) [ Time Frame: 12 months ]
    Evaluation will be performed using the Motor Function Measurement scale before and after 12 months of treatment with givinostat versus placebo
  • Mean change in 6 Minute Walking Test (6MWT) [ Time Frame: 12 months ]
    Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo
  • Proportion of patients with < 10% worsening in 6MWT at the end of study. [ Time Frame: 12 months ]
    Proportion of patients with < 10% worsening in 6MWT at the end of study.
  • Proportion of patients who lose the ability to rise from floor (Baseline through end of study). [ Time Frame: 12 months ]
    Proportion of patients who lose the ability to rise from floor (Baseline through
  • Proportion of patients who lose ambulation during the study [ Time Frame: 12 months ]
    Proportion of patients who lose ambulation during the study
  • Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM), [ Time Frame: 12 months ]
    Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo
  • Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36]) [ Time Frame: 12 months ]
    Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo
  • 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 ]
    Number of patients experiencing treatment-emergent adverse events (TEAEs)
  • Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS). [ Time Frame: 12 months ]
    Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS).
  • Changes from baseline to end of study of vital sign and clinical laboratory tests [ Time Frame: 12 months ]
    number of participants with abnormal laboratory values
  • Changes from baseline to end of study of physical examination [ Time Frame: 12 months ]
    number of participants with abnormal physical examination assessments
  • Mean change in Time Function Test [ Time Frame: 12 months ]
    Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo
Original Secondary Outcome Measures  ICMJE
 (submitted: July 31, 2017)
  • Mean change in fat fraction 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.
  • Mean change in fat fraction 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
  • 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
  • Mean change in other histology parameters (e.g. MFA%, % 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
  • 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
  • Mean change in 6 Minute Walking Test (6MWT) before and after 12 months of treatment with givinostat versus placebo [ Time Frame: 12 months ]
  • Proportion of patients with < 10% worsening in 6MWT at the end of study. [ Time Frame: 12 months ]
  • Proportion of patients who lose the ability to rise from floor (Baseline through end of study). [ Time Frame: 12 months ]
  • Proportion of patients who lose ambulation during the study [ Time Frame: 12 months ]
  • 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 ]
  • 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 ]
  • 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 ]
  • Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS). [ Time Frame: 12 months ]
  • Changes from baseline to end of study of clinical laboratory tests [ Time Frame: 12 months ]
    number of partecipant with abnormal laboratory values
  • Changes from baseline to end of study of vital signs [ Time Frame: 12 months ]
    number of partecipant with abnormal vital signs
  • Changes from baseline to end of study of physical examination [ Time Frame: 12 months ]
    number of partecipant with abnormal physical examination assessments
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy
Official Title  ICMJE 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)
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.
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.
  • 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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Becker Muscular Dystrophy
Intervention  ICMJE
  • Drug: givinostat
    suspension of givinostat (10 mg/mL)
    Other Name: Active Comparator: givinostat
  • Drug: placebo
    suspension manufactured to mimic givinostat
    Other Name: Placebo Comparator: placebo
Study Arms  ICMJE
  • Active Comparator: givinostat
    Givinostat oral suspension (10 mg/mL) twice daily in a fed state
    Intervention: Drug: givinostat
  • Placebo Comparator: placebo
    Placebo oral suspension (10 mg/mL) twice daily in a fed state
    Intervention: Drug: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 31, 2017)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2020
Estimated Primary Completion Date May 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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. 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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number: DSC/15/2357/53 + 39 02 6443 ext 2524 patientadvocacy@italfarmaco.com
Listed Location Countries  ICMJE Italy,   Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03238235
Other Study ID Numbers  ICMJE DSC/15/2357/53
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Italfarmaco
Study Sponsor  ICMJE Italfarmaco
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Giacomo Comi, MD Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
PRS Account Italfarmaco
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP