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

NCT ID: NCT03373968

Last Updated: 2026-01-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

206 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-10-24

Study Completion Date

2029-12-31

Brief Summary

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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.

Detailed Description

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GIVINOSTAT oral suspension (10 mg/mL) has to be administered orally as 2 oral doses daily while the subject is in a fed state. The starting dose of GIVINOSTAT in the present long term study will be the same that the subject was receiving at the end of the previous DMD GIVINOSTAT study.

As weight affects GIVINOSTAT exposures, the dosage will be modified based on subject weight according the rules detailed in the study protocol section 11.2.2.1.

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 meet the stopping criteria for platelets, the Investigator will have to reduce the dose of 1/3 or 20% less of the current dose as described in the study protocol section 10.5.1.3. During the first month of treatment, platelets count assessment will be performed weekly, while during the second month it will be performed every 2 weeks, in order to strictly monitor this parameter for safety reasons, with the exclusion of subjects coming from study DSC/11/2357/43 for which the first visit will be 4 months after the Visit 1/baseline visit.

Study drug should be permanently interrupted if any of the following occurs:

* severe drug-related diarrhoea (i.e., increase of ≥7 stools per day);
* any drug-related SAE;
* QTcF \>500 msec;
* platelets count ≤50 x 10\^9/L;
* white blood cells ≤2.0 x 10\^9/L;
* hemoglobin ≤8.0 g/dL; To avoid laboratory errors and anomalous values, test must be confirmed with a repeated test performed on the next working day. The treatment should be stopped until the retest result becomes available. If the repeated test is still under the stopping limit value, study drug must be permanently discontinued. If the repeated test is acceptable, the subject can resume treatment.

The Investigator will follow up the patient until resolution or acceptable stabilization of the event occurs and document all the relevant information, as applicable. After the resolution/stabilization of the event, the subject will be withdrawn from the study and the EOS Visit (see Section 12.1.10) will be performed.

Any decision relevant to the dose adjustment and/or modification of schedule of assessments can be discussed with the Medical Monitor, but the final decision remains with the Investigator only or its authorized designee.

Conditions

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Duchenne Muscular Dystrophy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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givinostat

Givinostat oral suspension (10 mg/mL) twice daily in a fed state

Group Type EXPERIMENTAL

Givinostat

Intervention Type DRUG

suspension of givinostat (10 mg/mL)

Interventions

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Givinostat

suspension of givinostat (10 mg/mL)

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. Aged ≥6 years old;
3. Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to localregulations);
4. 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 Criteria

1. 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;
2. Use of any current investigational drug other than Givinostat;
3. 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;
4. Have a diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD;
5. 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);
6. 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);
7. 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);
8. Have heart failure (New York Heart Association Class III or IV)
9. 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;
10. 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);
11. 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.
12. Have any hypersensitivity to the components of study medication;
13. Have a sorbitol intolerance or sorbitol malabsorption or have the hereditary form of fructose intolerance.
Minimum Eligible Age

7 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Cromsource

INDUSTRY

Sponsor Role collaborator

Italfarmaco

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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

Sacramento, California, United States

Site Status COMPLETED

Rady Children's Hospital center - UCSD Department of Neuroscience

San Diego, California, United States

Site Status COMPLETED

Connecticut Children's Medical Center, Neurology Division

Hartford, Connecticut, United States

Site Status COMPLETED

Child Health Research Institute

Gainesville, Florida, United States

Site Status COMPLETED

MD Rare Disease Research, LLC

Atlanta, Georgia, United States

Site Status ENROLLING_BY_INVITATION

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Site Status ENROLLING_BY_INVITATION

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

St Louis, Missouri, United States

Site Status COMPLETED

Shriners Hospitals for Children

Portland, Oregon, United States

Site Status COMPLETED

The Children's Hospital of Philadelphia Colket Translational Research Building

Philadelphia, Pennsylvania, United States

Site Status COMPLETED

Virginia Commonwealth University Childrens Hospital of Richmond at

Richmond, Virginia, United States

Site Status COMPLETED

University Hospitals Leuven, Neuromuscular Reference Centre, Child Neurology

Leuven, , Belgium

Site Status ENROLLING_BY_INVITATION

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

Liège, , Belgium

Site Status ENROLLING_BY_INVITATION

Kinsmen Research Centre - Alberta Children's Hospital

Calgary, Alberta, Canada

Site Status ENROLLING_BY_INVITATION

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

Vancouver, British Columbia, Canada

Site Status ENROLLING_BY_INVITATION

Holland Bloorview Kids Rehabilitation Hospital

Toronto, Ontario, Canada

Site Status ENROLLING_BY_INVITATION

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

Nantes, , France

Site Status ENROLLING_BY_INVITATION

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

Paris, , France

Site Status ENROLLING_BY_INVITATION

Universitätsklinikum Essen - Kinder-und Jugendmedizin Neuropadiatrie

Essen, , Germany

Site Status ENROLLING_BY_INVITATION

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

Hamburg, , Germany

Site Status ENROLLING_BY_INVITATION

Klinikum der Universitat Munchen, Campus Innenstadt, Lindwurmstr. 4

München, , Germany

Site Status ACTIVE_NOT_RECRUITING

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

Petah Tikva, , Israel

Site Status ENROLLING_BY_INVITATION

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

Genova, , Italy

Site Status RECRUITING

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

Messina, , Italy

Site Status ENROLLING_BY_INVITATION

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

Milan, , Italy

Site Status ACTIVE_NOT_RECRUITING

IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status ENROLLING_BY_INVITATION

Centro Clinico NeMO Fondazione Serena ONLUS Area SUD

Milan, , Italy

Site Status ENROLLING_BY_INVITATION

Ospedale Pediatrico Bambino Gesù, Malattie Neuromuscolari e Neurodegenerative

Roma, , Italy

Site Status RECRUITING

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

Roma, , Italy

Site Status ENROLLING_BY_INVITATION

Leiden University Medical Center LUMC, Albinusdreef 2

Leiden, , Netherlands

Site Status ENROLLING_BY_INVITATION

Radboud University Medical Centre

Nijmegen, , Netherlands

Site Status ENROLLING_BY_INVITATION

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

Belgrade, , Serbia

Site Status ENROLLING_BY_INVITATION

Neuromuscular Pathology Unit - Hospital Sant Joan de Déu

Esplugues de Llobregat, Barcellona, Spain

Site Status ENROLLING_BY_INVITATION

Hospital Materno-Infantil

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status ENROLLING_BY_INVITATION

Hospital Universitari i Politècnic La Fe - Servicio Neurologia

Valencia, , Spain

Site Status ENROLLING_BY_INVITATION

Alder Hey Children's Hospital NHS Trust

Liverpool, UK, United Kingdom

Site Status ENROLLING_BY_INVITATION

The Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust

Gobowen, , United Kingdom

Site Status ENROLLING_BY_INVITATION

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

London, , United Kingdom

Site Status ENROLLING_BY_INVITATION

The John Walton Muscular Dystrophy Research Centre

Newcastle upon Tyne, , United Kingdom

Site Status ENROLLING_BY_INVITATION

Countries

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United States Belgium Canada France Germany Israel Italy Netherlands Serbia Spain United Kingdom

Central Contacts

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Reference Study ID Number: DSC/14/2357/51

Role: CONTACT

+ 39 02 6443 ext. 2524

Facility Contacts

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Claudio Bruno, MD

Role: primary

+39 010 56362 2620

Enrico Bertini, MD

Role: primary

Francina Munell, MD

Role: primary

References

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McDonald CM, Guglieri M, Vucinic D, Acsadi G, Brandsema JF, Bruno C, Finanger EL, Harper A, Lobato ML, Masson R, Muelas N, Munell F, Nevo Y, Pereon Y, Phan H, Sansone VA, Scoto M, Willis T, Finkel RS, Vandenborne K, Cazzaniga S, Montrasio S, Alessi F, Bettica P, Mercuri E; Givinostat Study 51 Investigators; Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS) Investigators; ImagingDMD Investigators. Long-Term Evaluation of Givinostat in Duchenne Muscular Dystrophy, and Natural History Comparisons. Ann Clin Transl Neurol. 2025 Nov;12(11):2335-2348. doi: 10.1002/acn3.70165. Epub 2025 Aug 19.

Reference Type DERIVED
PMID: 40830818 (View on PubMed)

Other Identifiers

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DSC/14/2357/51

Identifier Type: -

Identifier Source: org_study_id

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