<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03238235</url>
  </required_header>
  <id_info>
    <org_study_id>DSC/15/2357/53</org_study_id>
    <nct_id>NCT03238235</nct_id>
  </id_info>
  <brief_title>Clinical Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Becker Muscular Dystrophy</brief_title>
  <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)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Italfarmaco</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Italfarmaco</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2, randomised, double-blind, placebo controlled study to evaluate the&#xD;
      micro-macroscopic effects on muscles, the safety and tolerability, and the efficacy of&#xD;
      givinostat in patients with Becker Muscular Dystrophy. Approximately 48 eligible patients&#xD;
      will be randomized in a 2:1 ratio to be treated with givinostat or placebo for a period of 12&#xD;
      months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Givinostat or placebo oral suspension (10 mg/mL) will be administered orally as 2 oral doses&#xD;
      daily while the subject is in fed state, according to the subject's weight.&#xD;
&#xD;
      Study drug should be permanently stopped if any of the following occur:&#xD;
&#xD;
        -  severe drug-related diarrhoea;&#xD;
&#xD;
        -  any drug-related Serious Adverse Event (SAE);&#xD;
&#xD;
        -  QTcorrected by Fridericia's formulas (QTcF) &gt;500 msec;&#xD;
&#xD;
        -  platelets (PLT) count ≤50 x 1.000.000.000/L (10E9/L);&#xD;
&#xD;
        -  White blood cell (WBC) ≤ 2.0 x 10E9/L;&#xD;
&#xD;
        -  Hemoglobin (Hb) ≤ 8.0 g/dL.&#xD;
&#xD;
      Study drug should be temporarily stopped if any of the following occur:&#xD;
&#xD;
        -  PLT count &lt;75 x 10E9/L but &gt;50 x 10E9/L;&#xD;
&#xD;
        -  WBC &lt; 3.0 x 10E9/L but &gt; 2.0 x 10E9/L;&#xD;
&#xD;
        -  Hb &lt; 10.0 g/dL but &gt; 8.0 g/dL;&#xD;
&#xD;
        -  moderate or severe diarrhoea.&#xD;
&#xD;
        -  tryglicerides &gt;300 mg/dL In case the study drug was temporarily stopped, the study drug&#xD;
           can be resumed at a level 20% smaller than the dose at which the Adverse Event leading&#xD;
           to temporary stop occurred, once platelets and/or WBC and/or Hb and/or tryglicerides are&#xD;
           normalized or when diarrhoea is mild&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 12, 2017</start_date>
  <completion_date type="Actual">March 19, 2021</completion_date>
  <primary_completion_date type="Actual">March 19, 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean change in total fibrosis (%)</measure>
    <time_frame>12 months</time_frame>
    <description>Mean change in total fibrosis (%) comparing the histology of muscle biopsies before and after 12 months of treatment with givinostat versus placebo</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean change in fat fraction of vastus lateralis and soleus</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed comparing Magnetic Resonance Spectroscopy (MRS) before and after 12 months of treatment with givinostat versus placebo.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in fat fraction of pelvic girdle and lower limb muscles</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed comparing Magnetic Resonance Imaging (MRI) before and after 12 months of treatment with givinostat versus placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean CSA of pelvic girdle and lower limb muscles</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed comparing MRI before and after 12 months of treatment with givinostat versus placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in other histology parameters (e.g. Muscle Fibers Area Fraction [MFAF]%, % of total fibrosis, regenerative fibers)</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed comparing the histology biopsies before and after 12 months of treatment with givinostat</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Motor Function Measurement (MFM)</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed using the Motor Function Measurement scale before and after 12 months of treatment with givinostat versus placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in 6 Minute Walking Test (6MWT)</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with &lt; 10% worsening in 6MWT at the end of study.</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of patients with &lt; 10% worsening in 6MWT at the end of study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who lose the ability to rise from floor (Baseline through end of study).</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of patients who lose the ability to rise from floor (Baseline through</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients who lose ambulation during the study</measure>
    <time_frame>12 months</time_frame>
    <description>Proportion of patients who lose ambulation during the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM),</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36])</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) from Baseline through end of study (EOS).</measure>
    <time_frame>12 months</time_frame>
    <description>Number of patients experiencing treatment-emergent adverse events (TEAEs)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS).</measure>
    <time_frame>12 months</time_frame>
    <description>Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to end of study of vital sign and clinical laboratory tests</measure>
    <time_frame>12 months</time_frame>
    <description>number of participants with abnormal laboratory values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline to end of study of physical examination</measure>
    <time_frame>12 months</time_frame>
    <description>number of participants with abnormal physical examination assessments</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in Time Function Test</measure>
    <time_frame>12 months</time_frame>
    <description>Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">51</enrollment>
  <condition>Becker Muscular Dystrophy</condition>
  <arm_group>
    <arm_group_label>givinostat</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Givinostat oral suspension (10 mg/mL) twice daily in a fed state</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo oral suspension (10 mg/mL) twice daily in a fed state</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>givinostat</intervention_name>
    <description>suspension of givinostat (10 mg/mL)</description>
    <arm_group_label>givinostat</arm_group_label>
    <other_name>Active Comparator: givinostat</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>suspension manufactured to mimic givinostat</description>
    <arm_group_label>placebo</arm_group_label>
    <other_name>Placebo Comparator: placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ambulant patients with BMD diagnosis confirmed by genetic testing.&#xD;
&#xD;
          2. Able and willing to give informed consent in writing.&#xD;
&#xD;
          3. Able to perform 6MWT at screening with a minimum distance of 200 m and maximum&#xD;
             distance of 450 m.&#xD;
&#xD;
          4. If in treatment with systemic corticosteroids and/or angiotensin-converting-enzyme&#xD;
             (ACE) inhibitor , and/or β or α adrenergic receptor blocker, no significant change in&#xD;
             dosage or dosing regimen (excluding changes related to body weight change) for a&#xD;
             minimum of 6 months immediately prior to start of study treatment.&#xD;
&#xD;
          5. Patients must be willing to use adequate contraception. Contraceptive methods must be&#xD;
             used from Randomization through 3 months after the last dose of study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Exposure to another investigational drug within 3 months prior to the start of study&#xD;
             treatment.&#xD;
&#xD;
          2. Use of any pharmacologic treatment, other than corticosteroids, that might have an&#xD;
             effect on muscle strength or function within 3 months prior to the start of study&#xD;
             treatment (e.g., growth hormone). Vitamin D, calcium, and any other supplements will&#xD;
             be allowed.&#xD;
&#xD;
          3. Surgery that might affect muscle strength or function within 3 months before study&#xD;
             entry or planned surgery at any time during the study.&#xD;
&#xD;
          4. Presence of other clinically significant disease that in the Investigator's opinion&#xD;
             could adversely affect the safety of the patient, making it unlikely that the course&#xD;
             of treatment or follow-up is completed, or could impair the assessment of study&#xD;
             results.&#xD;
&#xD;
          5. A diagnosis of other neurological diseases or presence of relevant somatic disorders&#xD;
             that are not related to BMD.&#xD;
&#xD;
          6. Platelet count, WBC count and hemoglobin at screening &lt; Lower Limit of Normal (LLN).&#xD;
             If laboratory screening results are &lt; LLN, platelet count, WBC count and hemoglobin&#xD;
             are to be repeated once, and if again &lt; LLN become exclusionary.&#xD;
&#xD;
          7. Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or&#xD;
             IV) or left ventricular ejection fraction &lt; 50% at screening or with heart transplant.&#xD;
&#xD;
          8. Current liver disease or impairment, including but not limited to elevated total&#xD;
             bilirubin (&gt; 1.5 x ULN), unless secondary to Gilbert's disease or pattern consistent&#xD;
             with Gilbert's disease.&#xD;
&#xD;
          9. Inadequate renal function, as defined by serum Cystatin C &gt; 2 x the upper limit of&#xD;
             normal (ULN). If the value is &gt; 2 x ULN, serum Cystatin C will be repeated once, and&#xD;
             if again &gt; 2 x ULN becomes exclusionary.&#xD;
&#xD;
         10. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human&#xD;
             immunodeficiency virus at screening.&#xD;
&#xD;
         11. Baseline corrected QTcF &gt; 450 msec, (as the mean of 3 consecutive readings 5 minutes&#xD;
             apart) or history of additional risk factors for torsades de pointes (e.g., heart&#xD;
             failure, hypokalemia, or family history of long QT syndrome).&#xD;
&#xD;
         12. Current psychiatric illness/social situations rendering the potential patient unable&#xD;
             to understand and comply with the muscle function tests and/or with the study protocol&#xD;
             procedures.&#xD;
&#xD;
         13. Hypersensitivity to the components of study medication.&#xD;
&#xD;
         14. Sorbitol intolerance or sorbitol malabsorption, or the hereditary form of fructose&#xD;
             intolerance.&#xD;
&#xD;
         15. Contraindications to muscle biopsy.&#xD;
&#xD;
         16. Contraindications to MRI/MRS (e.g., claustrophobia, metal implants, or seizure&#xD;
             disorder).&#xD;
&#xD;
         17. Hypertrygliceridemia (&lt;1.5 per upper limit of normal)* * at screening, patient with&#xD;
             hypertrygliceridemia can be enrolled if in stable treatment and with controlled level&#xD;
             of tryglicerides (i.e. within normal range) for at least 6 months&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Giacomo Comi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS</name>
      <address>
        <city>Milan</city>
        <zip>20122</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leiden University Medical Center LUMC</name>
      <address>
        <city>Leiden</city>
        <zip>ZH 2300 RC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 12, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>January 11, 2022</last_update_submitted>
  <last_update_submitted_qc>January 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">January 26, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Dystrophies</mesh_term>
    <mesh_term>Muscular Dystrophy, Duchenne</mesh_term>
  </condition_browse>
  <pending_results>
    <submitted>May 24, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03238235
org study id: DSC/15/2357/53
nct id: NCT03238235
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean change in total fibrosis (%)
time frame: 12 months
description: Mean change in total fibrosis (%) comparing the histology of muscle biopsies before and after 12 months of treatment with givinostat versus placebo
measure: Mean change in fat fraction of vastus lateralis and soleus
time frame: 12 months
description: Evaluation will be performed comparing Magnetic Resonance Spectroscopy (MRS) before and after 12 months of treatment with givinostat versus placebo.
measure: Mean change in fat fraction of pelvic girdle and lower limb muscles
time frame: 12 months
description: Evaluation will be performed comparing Magnetic Resonance Imaging (MRI) before and after 12 months of treatment with givinostat versus placebo
measure: Mean CSA of pelvic girdle and lower limb muscles
time frame: 12 months
description: Evaluation will be performed comparing MRI before and after 12 months of treatment with givinostat versus placebo
measure: Mean change in other histology parameters (e.g. Muscle Fibers Area Fraction [MFAF]%, % of total fibrosis, regenerative fibers)
time frame: 12 months
description: Evaluation will be performed comparing the histology biopsies before and after 12 months of treatment with givinostat
measure: Mean change in Motor Function Measurement (MFM)
time frame: 12 months
description: Evaluation will be performed using the Motor Function Measurement scale before and after 12 months of treatment with givinostat versus placebo
measure: Mean change in 6 Minute Walking Test (6MWT)
time frame: 12 months
description: Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo
measure: Proportion of patients with < 10% worsening in 6MWT at the end of study.
time frame: 12 months
description: Proportion of patients with < 10% worsening in 6MWT at the end of study.
measure: Proportion of patients who lose the ability to rise from floor (Baseline through end of study).
time frame: 12 months
description: Proportion of patients who lose the ability to rise from floor (Baseline through
measure: Proportion of patients who lose ambulation during the study
time frame: 12 months
description: Proportion of patients who lose ambulation during the study
measure: Mean change in muscle strength evaluated by knee extension, elbow flexion as measured by Hand Held Myometry (HHM),
time frame: 12 months
description: Evaluation will be performed before and after 12 months of treatment with givinostat versus placebo
measure: Mean changes in quality of life (assessed by the 36-item Short Form survey [SF36])
time frame: 12 months
description: Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo
measure: 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
description: Number of patients experiencing treatment-emergent adverse events (TEAEs)
measure: Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS).
time frame: 12 months
description: Type, incidence, and severity of TEAEs and SAEs (Baseline through EOS).
measure: Changes from baseline to end of study of vital sign and clinical laboratory tests
time frame: 12 months
description: number of participants with abnormal laboratory values
measure: Changes from baseline to end of study of physical examination
time frame: 12 months
description: number of participants with abnormal physical examination assessments
measure: Mean change in Time Function Test
time frame: 12 months
description: Evaluation will be performed before and after 12 months of treatment with givinostat as compared to placebo
arm group label: givinostat
arm group type: Active Comparator
description: Givinostat oral suspension (10 mg/mL) twice daily in a fed state
arm group label: placebo
arm group type: Placebo Comparator
description: Placebo oral suspension (10 mg/mL) twice daily in a fed state
intervention type: Drug
intervention name: givinostat
description: suspension of givinostat (10 mg/mL)
arm group label: givinostat
other name: Active Comparator: givinostat
intervention type: Drug
intervention name: placebo
description: suspension manufactured to mimic givinostat
arm group label: placebo
other name: Placebo Comparator: placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Giacomo Comi, MD
role: Principal Investigator
affiliation: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
facility: 
facility: 
country: Italy
country: Netherlands
responsible party type: Sponsor
mesh term: Muscular Dystrophies
mesh term: Muscular Dystrophy, Duchenne
submitted: May 24, 2023