Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02851797
Recruitment Status : Recruiting
First Posted : August 2, 2016
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Italfarmaco

Tracking Information
First Submitted Date  ICMJE July 27, 2016
First Posted Date  ICMJE August 2, 2016
Last Update Posted Date July 10, 2019
Actual Study Start Date  ICMJE June 1, 2017
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
mean change in 4 standard stairs climb [ Time Frame: 18 months ]
the primary endpoint is the mean change in 4 standard stairs climb test results before and after 18 months of treatment of givinostat versus placebo
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02851797 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2019)
  • Other functional test as 6MWT [ Time Frame: 18 months ]
    the mean change in 6MWT
  • time to rise from floor [ Time Frame: 18 months ]
    the mean change in time to rise from floor
  • Magnetic Resonance Spetroscopy [ Time Frame: 18 months ]
    the mean change in fat fraction of vastus lateralis muscles at MRS
  • North Star Ambulatory Assessment [ Time Frame: 18 months ]
    the mean change in North Star Ambulatory Assessment
  • Muscle strength evaluated by knee extension, elbow flexion [ Time Frame: 18 months ]
    the mean change of muscle strength evaluated by knee extension, elbow flexion as measured by hand-held myometry (HHM)
Original Secondary Outcome Measures  ICMJE
 (submitted: July 28, 2016)
  • Other functional test as 6MWT [ Time Frame: 18 months ]
    the mean change in 6MWT
  • time to rise from floor [ Time Frame: 18 months ]
    the mean change in time to rise from floor
  • Magnetic Resonance Spetroscopy [ Time Frame: 18 months ]
    the mean change in fat fraction of vastus lateralis muscles at MRS
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 Duchenne Muscular Dystrophy
Official Title  ICMJE Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
Brief Summary

it is a randomised, double blind, parallel group, placebo controlled study. A total of 213 male ambulant subjects will be randomised 2:1 (givinostat:placebo).

Subjects will be stratified for their concomitant use of steroids in 4 strata:

  1. Deflazacort daily regimen
  2. Deflazacort intermittent regimen
  3. Other steroids daily regimen
  4. Other steroids intermittent regimen. The study duration is planned for 19 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 child's weight.

Study drug should be permanently stopped if any of the following occur:

  • severe drug-related diarrhoea;
  • any drug-related Serious Adverse Event;
  • QTcF >500 msec;
  • platelets count ≤50 x 109/L.
  • white blood cells ≤2.0 x 109/L
  • hemoglobin ≤8.0 g/dL

Study drug should be temporarily stopped if any of the following occur:

  • platelets count <75 x 109/L but >50 x 109/L (the treatment should be temporarily stopped and a platelets count has to be performed and re-tested until platelets will be normalized);
  • moderate or severe diarrhoea.
  • white blood cell <3.0 x 109/L but >2.0 x 109/L (the treatment should be temporarily stopped and white blood cells have to be measured by 1 week and re-tested until white blood cells will be normalized);
  • hemoglobin <10.0 g/dL but > 8.0 g/dL (the treatment should be temporarily stopped and hemoglobin has to be measured by 1 week and re-tested until hemoglobin will be normalized);
  • Triglycerides >300 mg/dL (3.42 mmol/L) in fasting condition (the treatment should be temporarily stopped and triglycerides has to be measured every 2 weeks until triglycerides return to levels below 300mg/dL (3.42 mmol/L)

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 and/or white blood cell and/or hemoglobin are normalized and/or triglycerides return to levels below 300 mg/dL (3.42 mmol/L) or diarrhoea is mild.

Two interim analyses are planned and will be conducted by the IDMC in order to ensure study integrity.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: givinostat
    suspension of givinostat (10 mg/mL)
  • Drug: placebo
    suspension manufactured to mimic givinostat
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 28, 2016)
213
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Are an ambulant male aged ≥6 years at randomisation with DMD characteristic clinical symptoms or signs (e.g., proximal muscle weakness, Gowers' maneuver, elevated serum creatinine kinase level) already present at screening;
  2. Have DMD diagnosis confirmed by genetic testing;
  3. Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to local regulations);
  4. Are able to complete 2 Four Stairs Climb test (4SC) screening assessments; the results of these tests must be within ±1 second of each other;
  5. Have the mean of 2 screening 4SC assessments ≤8 seconds;
  6. Have time to rise from floor between ≥3 and <10 seconds at screening
  7. Have manual muscle testing (MMT) of quadriceps at screening Grade ≥

    - 3;

  8. Have used systemic corticosteroids for a minimum of 6 months immediately prior to the start of study treatment, with no significant change in corticosteroids type or dosage or dosing regimen (excluding changes related to body weight change) for a minimum of 6 months immediately prior to start of study treatment and a reasonable expectation that dosage and dosing regimen will not change significantly for the duration of the study.
  9. Subjects must be willing to use adequate contraception.

Exclusion Criteria:

  1. Have exposure to another investigational drug within 3 months prior to the start of study treatment;
  2. Have exposure to idebenone within 3 months prior to the start of study treatment;
  3. Have exposure to any dystrophin restoration product (e.g., Ataluren, Exon skipping) within 6 months prior to the start of study treatment;
  4. Use of any pharmacologic treatment, other than corticosteroids, that might have had 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 as long as their intake has been stable for 3 months prior to the start of study treatment; Testosterone will also be allowed if it is used as a replacement therapy for the treatment of delayed puberty, and testosterone dose and regimen have been stable for at least 6 months and circulating testosterone levels are within the normal ranges for the subject's age;
  5. Have surgery that might have an effect on muscle strength or function within 3 months before study entry or planned surgery at any time during the study;
  6. Ankle joint contractures due to a fixed loss of ≥10 degrees of dorsiflexion from plantagrade assuming a normal range of dorsiflexion of 20 degree;
  7. Change in contracture treatment such as serial casting, contracture control devices, night splints, stretching exercises (passive, active, self) within 3 months prior to enrollment, or expected need for such intervention during the study;
  8. Have presence of other clinically significant disease, which, in the Investigator's opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results;
  9. Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD;
  10. Have platelets count at screening < Lower Limit of Normal (LLN);
  11. Have symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction <50% at screening;
  12. Have a current or history of liver disease or impairment;
  13. Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN);
  14. Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit;
  15. Have a baseline QTcF >450 msec, or history of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, or family history of long QT syndrome);
  16. Have a psychiatric illness/social situations rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures;
  17. Have any known allergic reaction to givinostat or any of its excipients.
  18. Have any hypersensitivity to the components of study medication;
  19. Have a sorbitol intolerance or sorbitol malabsorption, or have the hereditary form of fructose intolerance.
  20. Have contraindications to MRI or MRS (e.g., claustrophobia, metal implants, or seizure disorder).

At the discretion of the Investigator, subjects not meeting inclusion/exclusion criteria may be re-screened twice with an interval of at least 3 months between assessments.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Reference Study ID Number EPYDIS (DSC/14/2357/48) +39 026443 ext 2524 patientadvocacy@italfarmaco.com
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02851797
Other Study ID Numbers  ICMJE EPYDIS (DSC/14/2357/48)
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Italfarmaco
Study Sponsor  ICMJE Italfarmaco
Collaborators  ICMJE Syneos Health
Investigators  ICMJE Not Provided
PRS Account Italfarmaco
Verification Date July 2019

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