RecruitingPhase 2Phase 3NCT03373968

Givinostat in Duchenne's Muscular Dystrophy Long-term Safety and Tolerability Study

Open Label, Long-term Safety, Tolerability, and Efficacy Study of GIVINOSTAT in All DMD Patients Who Have Been Previously Treated in One of the GIVINOSTAT Studies


Sponsor

Italfarmaco

Enrollment

206 participants

Start Date

Oct 24, 2017

Study Type

INTERVENTIONAL

Conditions

Summary

This is an open label, long-term safety, tolerability, and efficacy study of GIVINOSTAT in all DMD (Duchenne's muscular dystrophy) patients who have been previously treated in one of the GIVINOSTAT studies.


Eligibility

Sex: MALEMin Age: 7 Years

Inclusion Criteria11

  • Must have participated in one of the previous studies with GIVINOSTAT in DMD and have attended the End of Study Visit or must have been screened in study DSC/14/2357/48 and met:
  • had a baseline vastus lateralis muscle fat fraction (VL MFF) assessed by MRS in the range ≤5% or \>30%, i.e. included in"off-target" group,
  • never been randomized because, the enrollment in the off target group was completed.
  • Aged ≥6 years old;
  • Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to localregulations);
  • Subjects must be willing to use adequate contraception:
  • Contraceptive methods must since the previous GIVINOSTAT study through 3 months after the last dose of study drug, and include the following:
  • True abstinence (absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the subject.
  • Periodic abstinence (e.g. calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception.
  • Condom with spermicide and the female partner must use an acceptable method of contraception, such as an oral,
  • transdermal, injectable or implanted steroid-basedcontraceptive, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such asfor example cervical cap with spermicide jelly.

Exclusion Criteria13

  • Use of any pharmacologic treatment, other than corticosteroids, that might have had an effect on muscle strength or function within 3 months prior to be enrolled in this study (e.g., growth hormone); Vitamin D, calcium, and any other supplements will be allowed;
  • Use of any current investigational drug other than Givinostat;
  • 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;
  • Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD;
  • Have platelets count, White Blood Cell and Hemoglobin at screening \< Lower Limit of Normal (LLN)\* (for abnormal screening laboratory test results (\<LLN), the platelets count, White Blood Cell and Hemoglobin will be repeated once; if the repeat test result is still \<LLN, then exclusionary);
  • Have Triglycerides \> 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit\* (for abnormal screening laboratory test results (\>300 mg/dL), the triglycerides will be repeated once; if the repeat test result is still \>300 mg/dL, then exclusionary);
  • Have inadequate renal function, as defined by serum Cystatin C \>2 x the upper limit of normal (ULN) at screening visit\*. If the value is \>2 x ULN, the serum Cystatin C will be repeated once; if the repeated test result is still \>2 x ULN, the subject should be excluded);
  • Have heart failure (New York Heart Association Class III or IV)
  • Have a current liver disease or impairment, including but not limited to an elevated total bilirubin\* (i.e. \> 1.5 x ULN), unless secondary to Gilbert disease or pattern consistent with Gilbert's;
  • Have a baseline 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);
  • Have a psychiatric illness/social situation rendering the potential subject unable to understand and comply with the muscle function tests and/or with the study protocol procedures.
  • Have any hypersensitivity to the components of study medication;
  • Have a sorbitol intolerance or sorbitol malabsorption or have the hereditary form of fructose intolerance.

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Interventions

DRUGGivinostat

suspension of givinostat (10 mg/mL)


Locations(39)

University of California - Davis Medical Center - Devis Physical Medicine & Rehabilitation

Sacramento, California, United States

Rady Children's Hospital center - UCSD Department of Neuroscience

San Diego, California, United States

Connecticut Children's Medical Center, Neurology Division

Hartford, Connecticut, United States

Child Health Research Institute

Gainesville, Florida, United States

MD Rare Disease Research, LLC

Atlanta, Georgia, United States

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Washington University School of Medicine in St Louis Department of Neurology 660 S.Euclid Avenue, Campus Box 8111

St Louis, Missouri, United States

Shriners Hospitals for Children

Portland, Oregon, United States

The Children's Hospital of Philadelphia Colket Translational Research Building

Philadelphia, Pennsylvania, United States

Virginia Commonwealth University Childrens Hospital of Richmond at

Richmond, Virginia, United States

University Hospitals Leuven, Neuromuscular Reference Centre, Child Neurology

Leuven, Belgium

Hospital de La Citadelle, Centre de Référence des Maladies Neuromuscolaires (CRMN)

Liège, Belgium

Kinsmen Research Centre - Alberta Children's Hospital

Calgary, Alberta, Canada

The University of British Columbia, Children's and Womens Health Centre of BC Branch

Vancouver, British Columbia, Canada

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, Canada

CHU de Nantes - Hotel-Dieu - Hopital Nord Laennec, rez-de-chausse haut ail Ouest

Nantes, France

Hôpital Armand Trousseau I-Motion - Plateforme d'essais cliniques pédiatriques Bâtiment Lemariey - Porte 20 * 2ème étage 26 Avenue du Dr Arnold Nette

Paris, France

Universitätsklinikum Essen - Kinder-und Jugendmedizin Neuropadiatrie

Essen, Germany

Klinik- und Poliklinik fur Kinder- und Jugendmedizin, Universitatsklinikum HamburgEppendorf, Martinistr. 52

Hamburg, Germany

Klinikum der Universitat Munchen, Campus Innenstadt, Lindwurmstr. 4

München, Germany

Institute of Neurology - Schneider Children's Medical Center of Israel Kaplan, 14

Petah Tikva, Israel

U.O.S.D. Centro Traslazionale di Miologia e Patologie Neurodegenerative, Building 16 - ground floor IRCCS Istituto Giannina Gaslini,

Genova, Italy

A.O.U. Policlinico G. Martino, U.O.C. Neurologia e Malattie Neuromuscolari

Messina, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano, UOS di Neurologia Pediatrica

Milan, Italy

IRCCS Istituto Neurologico Carlo Besta

Milan, Italy

Centro Clinico NeMO Fondazione Serena ONLUS Area SUD

Milan, Italy

Ospedale Pediatrico Bambino Gesù, Malattie Neuromuscolari e Neurodegenerative

Roma, Italy

Fondazione Policlinico Universitario "A.Gemelli", UOC Neuropsichiatria Infantile

Roma, Italy

Leiden University Medical Center LUMC, Albinusdreef 2

Leiden, Netherlands

Radboud University Medical Centre

Nijmegen, Netherlands

Clinic of Neurology and Psychiatry for Children and Youth - Neurology Department Dr. Subotic 6a,

Belgrade, Serbia

Neuromuscular Pathology Unit - Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcellona, Spain

Hospital Materno-Infantil

Barcelona, Spain

Hospital Universitario Virgen del Rocio

Seville, Spain

Hospital Universitari i Politècnic La Fe - Servicio Neurologia

Valencia, Spain

Alder Hey Children's Hospital NHS Trust

Liverpool, UK, United Kingdom

The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust

Gobowen, United Kingdom

UCL Great Ormond Street Institute of Child Health, Dubowitz Neuromuscular Centre and MRC Centre for NMD

London, United Kingdom

The John Walton Muscular Dystrophy Research Centre

Newcastle upon Tyne, United Kingdom

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