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Trial record 3 of 24 for:    Duchenne netherlands dmd

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02851797
Recruitment Status : Active, not recruiting
First Posted : August 2, 2016
Last Update Posted : September 21, 2020
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Italfarmaco

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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: givinostat Drug: placebo Phase 3

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 10^9/L.
  • white blood cells ≤2.0 x 10^9/L
  • hemoglobin ≤8.0 g/dL

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

  • moderate or severe diarrhoea.
  • platelets count <75 x 10^9/L but >50 x 10^9/L (the treatment should be temporarily stopped and a platelets count has to be performed and re-tested until platelets will be normalized);
  • white blood cell <3.0 x 10^9/L but >2.0 x 10^9/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 20% 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.

In addition, in case a subject will have a consistent (e.g., at least 2 consecutive evaluations) platelets count ≤150 x 10^9/L and not meeting the stopping criteria for platelets, the Investigator will have to reduce the dose by 20% of the current dose.

Only one dose reduction is allowed during the treatment period.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 169 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Givinostat in Ambulant Patients With Duchenne Muscular Dystrophy
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022


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)

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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Other functional test as 6MWT [ Time Frame: 18 months ]
    the mean change in 6MWT

  2. time to rise from floor [ Time Frame: 18 months ]
    the mean change in time to rise from floor

  3. Magnetic Resonance Spetroscopy [ Time Frame: 18 months ]
    the mean change in fat fraction of vastus lateralis muscles at MRS

  4. North Star Ambulatory Assessment [ Time Frame: 18 months ]
    the mean change in North Star Ambulatory Assessment

  5. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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.


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): NCT02851797


Locations
Hide Hide 42 study locations
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United States, California
Neuromuscular Research Center UC Davis Department of Physical Medicine and Rehabilitation
Davis, California, United States, 95817
Rady Children's Hospital center - UCSD Department of Neuroscience
San Diego, California, United States, 92123
United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center - Division Neurology
Hartford, Connecticut, United States, 06106
United States, Florida
Child Health Research Institute - Department of Pediatrics
Gainesville, Florida, United States, 32610
Nemours Children's Hospital
Orlando, Florida, United States, 32827
United States, Georgia
MD Rare Disease Research, LLC
Atlanta, Georgia, United States, 30318
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Minnesota
University of Minnesota - Department of Neurology
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Washington University School of Medicine in St Louis - Department of Neurology
Saint Louis, Missouri, United States, 63110
United States, Oregon
Shriners Hospitals for Children
Portland, Oregon, United States, 97239
United States, Pennsylvania
The Children's Hospital of Philadelphia Colket Translational Research Building
Philadelphia, Pennsylvania, United States, 19104
United States, Virginia
Virginia Commonwealth University Childrens Hospital of Richmond at Virginia Commonwealth University
Richmond, Virginia, United States, 23298
Belgium
University Hospitals Leuven, Neuromuscular Reference Centre, Child Neurology
Leuven, Belgium, 03000
Hospital de La Citadelle, Centre de Référence des Maladies Neuromuscolaires (CRMN)
Liege, Belgium, 04000
Canada, Alberta
Kinsmen Research Centre - Alberta Children's Hospital - Alberta Health Services
Calgary, Alberta, Canada, T3B6A8
Canada, British Columbia
The University of British Columbia, Children's and Womens Health Centre of BC Branch
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
Holland Bloorview Kids Rehabilitation Hospital
Toronto, Ontario, Canada, M4G1R8
France
CHU de Nantes - Hotel-Dieu - Hopital Nord Laennec, rez-de-chausse haut ail Ouest
Nantes, France, 44093
Hopital Armand Trousseau I-Motion, Plateforme d'essais cliniques pédiatriques
Paris, France, 75012
Germany
Universitatsklinikum Essen - Kinder und Jugendmedizin Neuropadiatrie
Essen, Germany, 45122
Klinik un Policlinik fur Kinder und Jugendmedizin - Universitatsklinikum Hamburg Eppendorf
Hamburg, Germany, 20246
Klinikum der Uniersitat Munchen - Campus Innenstadt
Munchen, Germany, 80337
Israel
Institute of Neurology - Schneider Children's Medical Center of Israel Kaplan, 14
Petach-Tikva, Israel, 4920235
Italy
IRCCS Istituto G.Gaslini, U.O.S.D. Centro Traslazionale di Miologia e Patologie Neurodegenerative
Genova, Italy, 16147
A.O.U. Policlinico G. Martino, U.O.C. Neurologia e Malattie Neuromuscolari
Messina, Italy, 98125
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS di Neurologia Pediatrica
Milano, Italy, 20122
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milano, Italy, 20133
Centro Clinico NeMO Fondazione Serena ONLUS Area SUD
Milano, Italy, 20162
Ospedale Pediatrico Bambin Gesù, Malattie Neuromuscolari e Neurodegenerative
Roma, Italy, 00146
Fondazione Policlinico Universitario "A.Gemelli", UOC Neuropsichiatria Infantile
Roma, Italy, 00168
Netherlands
Leiden University Medical Center LUMC
Leiden, Netherlands, ZH 2300 RC
Radboud University Medical Centre
Nijmegen, Netherlands, 6500
Serbia
Clinic of Neurology and Psychiatry for Children and Youth - Neurology Department Dr. Subotic 6a,
Belgrade, Serbia, 11000
Spain
Hospital Sant Joan de Déu - Neuromuscular Pathology Unit
Esplugues de Llobregat, Barcelona, Spain, 08950
Hospital Materno-Infantil - Passeig de la Vall d'Hebron
Barcelona, Spain, 08035
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital Universitari i Politécnic de la Fe - Servicio Neurologia
Valencia, Spain, 46026
United Kingdom
Alder Hey Children's Hospital NHS Trust
Liverpool, United Kingdom, L12 2AP
UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre and MRC Centre for NMD
London, United Kingdom, EC1N 1EH
The John Walton Muscular Dystrophy Research Centre - Freeman Hospital - Newcastle University - Institute of Genetic Medicine
Newcastle upon Tyne, United Kingdom, NE1 3BZ
The Robert Jones and Agnes Hunt Orthopaedic Hospital - NHS Foundation Trust
Oswestry, United Kingdom, SY 10 7AG
Sponsors and Collaborators
Italfarmaco
Syneos Health
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Responsible Party: Italfarmaco
ClinicalTrials.gov Identifier: NCT02851797    
Other Study ID Numbers: EPYDIS (DSC/14/2357/48)
First Posted: August 2, 2016    Key Record Dates
Last Update Posted: September 21, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked