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

Completed · Phase 3 · Has a placebo group

Conditions studied: Duchenne Muscular Dystrophy

In brief

Primary Objective The primary objective of the study was to establish the effects of givinostat versus placebo administered chronically over 18 months to slow disease progression in ambulant DMD subjects. Secondary Objectives The secondary objectives of this study were: * To assess the safety and tolerability of givinostat versus placebo administered chronically in DMD subjects * To evaluate the PK profile of givinostat administered chronically in DMD subjects * To evaluate the impact on quality of life (QoL) and activities of daily living of givinostat versus placebo administered chronically.

Key facts

Study ID

NCT02851797

Run by

Italfarmaco

People needed

179

Starts

2017-06-06

Expected to finish

2022-02-22

Last updated by the study team

2023-02-02

Who can join

Age: 6 and older, up to 17. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• 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;
• Have DMD diagnosis confirmed by genetic testing;
• Are able to give informed assent and/or consent in writing signed by the subject and/or parent/legal guardian (according to local regulations);
• 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;
• Have the mean of 2 screening 4SC assessments ≤8 seconds;
• Have time to rise from floor between ≥3 and <10 seconds at screening
• Have manual muscle testing (MMT) of quadriceps at screening Grade ≥- 3;
• 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.
• Subjects must be willing to use adequate contraception.

You may not qualify if…

• Have exposure to another investigational drug within 3 months prior to the start of study treatment;
• Have exposure to idebenone within 3 months prior to the start of study treatment;
• Have exposure to any dystrophin restoration product (e.g., Ataluren, Exon skipping) within 6 months prior to the start of study treatment;
• 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;
• 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;
• Loss of ≥30 degrees of plantar flexion from the normal range of movement at the ankle joint due to contracture (i.e. fixed loss of more than 10 degrees of plantar flexion from plantigrade, assuming normal range of dorsiflexion of 20 degrees;
• 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;
• 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 at screening < Lower Limit of Normal (LLN);
• Have symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) or left ventricular ejection fraction <50% at screening;
• Have a current or history of liver disease or impairment;
• Have inadequate renal function, as defined by serum Cystatin C >2 x the upper limit of normal (ULN);
• Have Triglycerides > 300 mg/dL (3.42 mmol/L) in fasting condition at screening visit;
• Have a positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening15.
• 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);
• 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;
• Have any hypersensitivity to the components of study medication;
• Have a sorbitol intolerance or sorbitol malabsorption, or have the hereditary form of fructose intolerance.
• 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.

Where it is running

• Neuromuscular Research Center UC Davis Department of Physical Medicine and Rehabilitation — Davis, California, United States
• Rady Children's Hospital center - UCSD Department of Neuroscience — San Diego, California, United States
• Children's Hospital Colorado — Aurora, Colorado, United States
• Connecticut Children's Medical Center - Division Neurology — Hartford, Connecticut, United States
• Child Health Research Institute - Department of Pediatrics — Gainesville, Florida, United States
• Nemours Children's Hospital — Orlando, Florida, United States
• MD Rare Disease Research, LLC — Atlanta, Georgia, United States
• University of Iowa Children's Hospital — Iowa City, Iowa, United States
• University of Minnesota - Department of Neurology — Minneapolis, Minnesota, United States
• Washington University School of Medicine in St Louis - Department of Neurology — 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 Virginia Commonwealth University — 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 - Alberta Health Services — 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
• Hopital Armand Trousseau I-Motion, Plateforme d'essais cliniques pédiatriques — Paris, France
• Universitatsklinikum Essen - Kinder und Jugendmedizin Neuropadiatrie — Essen, Germany
• Klinik un Policlinik fur Kinder und Jugendmedizin - Universitatsklinikum Hamburg Eppendorf — Hamburg, Germany
• Klinikum der Uniersitat Munchen - Campus Innenstadt — München, Germany
• Institute of Neurology - Schneider Children's Medical Center of Israel Kaplan, 14 — Petah Tikva, Israel
• IRCCS Istituto G.Gaslini, U.O.S.D. Centro Traslazionale di Miologia e Patologie Neurodegenerative — Genova, Italy

Full record on ClinicalTrials.gov

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