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Trial record 3 of 25 for:    Duchenne netherlands dmd
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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 : June 17, 2020
Sponsor:
Collaborator:
Syneos Health
Information provided by (Responsible Party):
Italfarmaco

Study Description
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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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 213 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

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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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)


Eligibility Criteria
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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.

Contacts and Locations
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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


Contacts
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Contact: Reference Study ID Number EPYDIS (DSC/14/2357/48) +39 026443 ext 2524 patientadvocacy@italfarmaco.com

Locations
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United States, California
Neuromuscular Research Center UC Davis Department of Physical Medicine and Rehabilitation Recruiting
Davis, California, United States, 95817
Contact: Erica Goude       emgoude@ucdavis.edu   
Principal Investigator: Craig McDonald, MD         
David Geffen School of Medicine - UCLA Neurology Withdrawn
Los Angeles, California, United States, 90095
Rady Children's Hospital center - UCSD Department of Neuroscience Recruiting
San Diego, California, United States, 92123
Contact: Jessica Reit       jreit@ucsd.edu   
Principal Investigator: Chamindra Konersman, MD         
United States, Colorado
Children's Hospital Colorado Terminated
Aurora, Colorado, United States, 80045
United States, Connecticut
Connecticut Children's Medical Center - Division Neurology Recruiting
Hartford, Connecticut, United States, 06106
Contact: Vikki Palmer       VPalmer@connecticutchildrens.org   
Principal Investigator: Gyula Acsadi, MD         
United States, Florida
Child Health Research Institute - Department of Pediatrics Recruiting
Gainesville, Florida, United States, 32610
Contact: Kim Gee       geekim@peds.ufl.edu   
Principal Investigator: Barry Byrne, MD         
Nemours Children's Hospital Recruiting
Orlando, Florida, United States, 32827
Contact: Virginia Rizzo, MD       Virginia.Rizzo@nemours.org   
Principal Investigator: Richard Finkel, MD         
United States, Georgia
MD Rare Disease Research, LLC Recruiting
Atlanta, Georgia, United States, 30318
Contact: Marcial Almaraz       marcial.almaraz@rarediseasesresearch.com   
Principal Investigator: Han Phan, MD         
United States, Iowa
University of Iowa Children's Hospital Recruiting
Iowa City, Iowa, United States, 52242
Contact: Corey McDaniel       corey-mcdaniel@uiowa.edu   
Principal Investigator: Katherine Mathews, MD         
United States, Michigan
Wayne State University - University Pediatrics - Children's Hospital of Michigan Withdrawn
Detroit, Michigan, United States, 48201
United States, Minnesota
University of Minnesota - Department of Neurology Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Emily Vollbrecht       vollb007@umn.edu   
Principal Investigator: Georgios Manousakis, MD         
United States, Missouri
Washington University School of Medicine in St Louis - Department of Neurology Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Alyssa Sonsoucie       amsonsoucie@wustl.edu   
Principal Investigator: Craig Zaidman, MD         
United States, Oregon
Shriners Hospitals for Children Recruiting
Portland, Oregon, United States, 97239
Contact: Cassandra Black       ceb@shcc.org   
Principal Investigator: Erika Finanger, MD         
United States, Pennsylvania
The Children's Hospital of Philadelphia Colket Translational Research Building Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Khrystine Ford    267-425-0158    fordka@email.chop.edu   
Principal Investigator: John Brandsema, MD         
United States, Virginia
Virginia Commonwealth University Childrens Hospital of Richmond at Virginia Commonwealth University Recruiting
Richmond, Virginia, United States, 23298
Contact: Kathryn O'Hara, MD       kathryn.ohara@vcuhealth.org   
Principal Investigator: Amy Harper, MD         
Belgium
University Hospitals Leuven, Neuromuscular Reference Centre, Child Neurology Recruiting
Leuven, Belgium, 03000
Contact: Nathalie Goemans, MD       nathalie.goemans@uzleuven.be   
Principal Investigator: Nathalie Goemans, MD         
Hospital de La Citadelle, Centre de Référence des Maladies Neuromuscolaires (CRMN) Recruiting
Liege, Belgium, 04000
Contact: Laurent Servais, MD       l.servais@institut-myologie.org   
Principal Investigator: Laurent Servais, MD         
Canada, Alberta
Kinsmen Research Centre - Alberta Children's Hospital - Alberta Health Services Recruiting
Calgary, Alberta, Canada, T3B6A8
Contact: Jean Mah, MD       Jean.Mah@albertahealthservices.ca   
Principal Investigator: Jean Mah, MD         
Canada, British Columbia
The University of British Columbia, Children's and Womens Health Centre of BC Branch Recruiting
Vancouver, British Columbia, Canada, V6H 3V4
Contact: Kathryn Selby, MD       kselby@cw.bc.ca   
Principal Investigator: Kathryn Selby, MD         
Canada, Ontario
Holland Bloorview Kids Rehabilitation Hospital Recruiting
Toronto, Ontario, Canada, M4G1R8
Contact: Laura McAdam       lmcadam@hollandbloorview.ca   
Principal Investigator: Laura McAdam, MD         
France
CHU de Nantes - Hotel-Dieu - Hopital Nord Laennec, rez-de-chausse haut ail Ouest Recruiting
Nantes, France, 44093
Contact: Yann Pereon, MD       yann.pereon@univ-nantes.fr   
Principal Investigator: Yann Pereon, MD         
Hopital Armand Trousseau I-Motion, Plateforme d'essais cliniques pédiatriques Recruiting
Paris, France, 75012
Contact: Odile Boespflug-Tanguy, MD       odile.boespflug-tanguy@aphp.fr   
Principal Investigator: Odile Boespflug-Tanguy, MD         
Germany
Universitatsklinikum Essen - Kinder und Jugendmedizin Neuropadiatrie Recruiting
Essen, Germany, 45122
Contact: Ulrike Schara, MD       ulrike.schara@uk-essen.de   
Principal Investigator: Ulrike Schara, MD         
Klinik un Policlinik fur Kinder und Jugendmedizin - Universitatsklinikum Hamburg Eppendorf Recruiting
Hamburg, Germany, 20246
Contact: Jessika Johannssen, MD       j.johannsen@uke.de   
Principal Investigator: Jessika Johannssen, MD         
Klinikum der Uniersitat Munchen - Campus Innenstadt Recruiting
Munchen, Germany, 80337
Contact: Astrid Blaschek, MD       Astrid.Blaschek@med.uni-muenchen.de   
Principal Investigator: Wolfgang Muller-Felber, MD         
Israel
Institute of Neurology - Schneider Children's Medical Center of Israel Kaplan, 14 Recruiting
Petach-Tikva, Israel, 4920235
Contact: Liraz Kraus, SC    972-3-9253398    lirazkr@clalit.org.il   
Contact: Lee Bareket-Kisler, SC    972-3-9253398    leek1@clalit.org.il   
Principal Investigator: Yoram Nevo, MD         
Italy
IRCCS Istituto G.Gaslini, U.O.S.D. Centro Traslazionale di Miologia e Patologie Neurodegenerative Recruiting
Genova, Italy, 16147
Contact: Claudio Bruno, MD       claudiobruno@ospedale-gaslini.ge.it   
Principal Investigator: Claudio Bruno, MD         
A.O.U. Policlinico G. Martino, U.O.C. Neurologia e Malattie Neuromuscolari Recruiting
Messina, Italy, 98125
Contact: Giuseppe Vita, MD       vitag@unime.it   
Principal Investigator: Giuseppe Vita, MD         
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS di Neurologia Pediatrica Recruiting
Milano, Italy, 20122
Contact: Giacomo Comi, MD       giacomo.comi@unimi.it   
Principal Investigator: Giacomo Comi, MD         
Fondazione IRCCS Istituto Neurologico Carlo Besta Recruiting
Milano, Italy, 20133
Contact: Riccardo Masson, MD       Riccardo.Masson@istituto-besta.it   
Principal Investigator: Riccardo Masson, MD         
Centro Clinico NeMO Fondazione Serena ONLUS Area SUD Recruiting
Milano, Italy, 20162
Contact: Valeria Sansone, MD    0291433734    valesans65@gmail.com   
Principal Investigator: Valeria Sansone, MD         
Ospedale Pediatrico Bambin Gesù, Malattie Neuromuscolari e Neurodegenerative Recruiting
Roma, Italy, 00146
Contact: Enrico Bertini, MD       enricosilvio.bertini@opbg.net   
Principal Investigator: Enrico Bertini, MD         
Fondazione Policlinico Universitario "A.Gemelli", UOC Neuropsichiatria Infantile Recruiting
Roma, Italy, 00168
Contact: Eugenio Mercuri, MD       eumercuri@gmail.com   
Contact       eugeniomaria.mercuri@policlinicogemelli.it   
Principal Investigator: Eugenio Mercuri, MD         
Netherlands
Leiden University Medical Center LUMC Recruiting
Leiden, Netherlands, ZH 2300 RC
Contact: Martha Mosselman, MD       Duchenne@lumc.nl   
Principal Investigator: Erik Niks, MD         
Radboud University Medical Centre Recruiting
Nijmegen, Netherlands, 6500
Contact: Imelda de Groot, MD       Imelda.deGroot@radboudumc.nl   
Principal Investigator: Imelda de Groot, MD         
Serbia
Clinic of Neurology and Psychiatry for Children and Youth - Neurology Department Dr. Subotic 6a, Recruiting
Belgrade, Serbia, 11000
Contact: Ana Kosac, SC    00381 11 265 8355    kosacana@gmail.com   
Principal Investigator: Vedrana Milic Rasic, MD         
Spain
Hospital Sant Joan de Déu - Neuromuscular Pathology Unit Recruiting
Esplugues de Llobregat, Barcelona, Spain, 08950
Contact: Andres Nascimento, MD       anascimento@sjdhospitalbarcelona.org   
Principal Investigator: Andres Nascimento, MD         
Hospital Materno-Infantil - Passeig de la Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Francina Munell, MD       francina.munell@vhir.org   
Principal Investigator: Francina Munell, MD         
Hospital Universitario Virgen del Rocio Recruiting
Sevilla, Spain, 41013
Contact: Francisco Javier Molina Ortega, ND    +34 669 393637    f.molina@fyamedical.com   
Principal Investigator: Marcos Madruga Garrido, MD         
Hospital Universitari i Politécnic de la Fe - Servicio Neurologia Recruiting
Valencia, Spain, 46026
Contact: Juan Jesus Vilchez, MD       vilchez_jje@gva.es   
Principal Investigator: Juan Jesus Vilchez, MD         
United Kingdom
Alder Hey Children's Hospital NHS Trust Recruiting
Liverpool, United Kingdom, L12 2AP
Contact: Nadia Ismail       nadia.ismail@alderhey.nhs.uk   
Principal Investigator: Stefan Spinty, MD         
UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre and MRC Centre for NMD Recruiting
London, United Kingdom, EC1N 1EH
Contact: Mariacristina Scoto, MD       m.scoto@ucl.ac.uk   
Principal Investigator: Mariacristina Scoto, MD         
The John Walton Muscular Dystrophy Research Centre - Freeman Hospital - Newcastle University - Institute of Genetic Medicine Recruiting
Newcastle upon Tyne, United Kingdom, NE1 3BZ
Contact: Volker Straub, MD       volker.straub@newcastle.ac.uk   
Principal Investigator: Michaela Guglieri, MD         
The Robert Jones and Agnes Hunt Orthopaedic Hospital - NHS Foundation Trust Recruiting
Oswestry, United Kingdom, SY 10 7AG
Contact: Sarah Turner, MD       Sarah.Turner2@rjah.nhs.uk   
Principal Investigator: Tracey Willis, MD         
Sponsors and Collaborators
Italfarmaco
Syneos Health
More Information
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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: June 17, 2020
Last Verified: June 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