This is a randomised, double-blind, placebo-controlled, multicentre study to evaluate the efficacy, safety, and tolerability of givinostat in non-ambulant male paediatric (aged 9 to \<18 years) patients with DMD. 138 patients will be randomised 2:1 to givinostat or placebo and will be treated for 18 months.
* Planned screening duration: approximately 4 weeks (±14 days) * Planned treatment duration: 18 months (approximately 72 weeks) * Planned follow-up duration: 4 weeks (±7 days) (for patients not participating in the long-term safety study) * Total duration of study participation: up to 83 weeks (ie, 20-21 months)
Children and adolescent males aged ≥ 9 to <18 years at screening (patients ≥ 18 years of age at screening will not be enrolled into the study)
Are able to give informed assent and/or consent in writing signed by the patient and/or parent/legal guardian (according to local regulations)
A genetic diagnosis of DMD
Unable to perform the 10-meter walk/run test (10MWT), or
Exposure to another investigational drug within 3 months prior to start of study treatment.
Have exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study treatment
Having received any gene therapy (eg, AAV Micro-dystrophin delivery) prior to start of study treatment
Use of any pharmacologic treatment or supplement (other than corticosteroids), that might have had an effect on muscle strength or function within 3 months prior to the start of study treatment (eg, growth hormone); vitamin D, calcium and any other supplements will be allowed
Parallel
Givinostat
DrugGivinostat has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose could be reduced based on predefined safety rules.
Placebo
DrugPlacebo, manufactured to mimic givinostat, has to be administered twice daily in a fed state according to a flexible dose regimen based on patient weight. Starting dose could be reduced based on predefined safety rules.
Change of Performance of Upper Limb 2.0 (PUL) total score at 18 months of treatment of givinostat compared to placebo group.
The PUL examines 3 major "dimensions" of upper extremity function: shoulder, middle, and distal functions. It includes 22 scored items; a score of 42 (12 for shoulder; 17 for mid-level, and 13 for distal) indicates the highest level of independent function and 0 the lowest.
Change from baseline of Peak Expiratory Flow percent predicted (PEF%p) at 18 months of treatment of givinostat compared to placebo group
Change from baseline of Forced Vital Capacity percent predicted (FVC%p) at 18 months of treatment of givinostat compared to placebo group
Cumulative loss of PUL total score over 18 months of treatment of givinostat compared to placebo group.
Type, incidence, and severity of treatment-emergent adverse events
Change from baseline of Fat Fraction of Deltoid and Biceps brachii using Dixon technique at 18 months of treatment of givinostat compared to placebo group
Proportion of responders of givinostat compared to placebo group
Responders are defined as patients who did not change their baseline PUL entry score at the EOS
Change from baseline of shoulder, elbow and distal level domains of PUL at 18 months of treatment of givinostat compared to placebo group
Change from baseline in muscle strength (eg, elbow flexion) evaluated by hand held myometry at 18 months of treatment of givinostat compared to placebo group
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Italfarmaco
Lead sponsor
Fortrea
Collaborator
