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Italfarmaco - ULYSSES
Randomised, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy (ULYSSES)
Hub Summary
The main objective of this study is to demonstrate the efficacy of givinostat in reducing muscle decline in non-ambulant patients aged 9-17 with Duchenne Muscular Dystrophy. Additional objectives are the evaluation of safety, tolerability of the drug and further exploration of efficacy of givinostat in non-ambulant DMD population.
Study Number: NCT05933057
Description by Italfarmaco
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. It is anticipated that 138 patients will be randomised 2:1 to givinostat or placebo and will be treated for 18 months with an oral suspension of study drug twice daily (bid) in a fed state.
Primary Objective of the study is to demonstrate the efficacy of givinostat in reducing muscle decline in non-ambulant DMD patients, as measured by Performance of the Upper Limb (PUL) 2.0.
Secondary Objectives of the study are to evaluate the safety and tolerability of givinostat in non-ambulant DMD patients, and to further explore the efficacy of givinostat in non-ambulant DMD patients.
Primary Outcome Measures
Change of Performance of Upper Limb 2.0 (PUL) total score after 18 months of treatment of givinostat compared to placebo group. [ Time Frame: Baseline and 18 months ]
The PUL examines 3 major "dimensions" of upper extremity function: shoulder, middle, and distal functions. It includes 21 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.
Can I take part?
Inclusion Criteria
- Children and adolescent males aged ≥ 9 to <18 years at screening
- Are able to give informed assent (ie, parent/legal guardian) and/or consent, according to local regulations
- A genetic diagnosis of DMD
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Non-ambulant defined as being wheelchair bound and:
- Unable to perform the 10-meter walk/run test (10MWT), or
- Unable to complete the 10MWT in 30 seconds or less, without any support or devices
- Performance of the Upper Limb test (PUL version 2.0) entry item scores 3 to 6
- If on medication for DMD-associated cardiomyopathy (eg, ACE inhibitor, β-blocker, diuretics), stable for ≥1 month immediately prior to start of study treatment, if any
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Stable corticosteroids, defined as:
- Receiving systemic corticosteroids for a minimum of 6 months immediately prior to start of study treatment
- No significant change in dose or dosing regimen (except for adjustments due to body weight change) for a minimum of 6 months immediately prior to start of study treatment
- Willing to use adequate contraception. Effective contraceptive methods must be used from randomisation visit through 3 months after the last dose of study drug.
Exclusion Criteria
- 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, Adeno-associated viruses 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)
- Use of testosterone, unless used as a replacement therapy for the treatment of delayed puberty. The testosterone dose and regimen should be stable within 6 months prior to the start of study treatment, and circulating testosterone levels should be within the normal ranges for the patient's age
- Elbow-flexion contractures >30° in the dominant arm
- Inability to perform consistent PUL 2.0 measurement within ±2 points without shoulder domain or within ±3 points with shoulder domain during paired testing at screening
- Forced Vital Capacity (FVC) % of predicted <40%
- Requirement for daytime ventilator assistance. Note: Night ventilator assistance and use of bi-level positive airway pressure therapy is allowed
- Episode of respiratory failure within the 8 weeks prior to screening
- Symptomatic cardiomyopathy or heart failure and/or left ventricular ejection fraction <45%
- Baseline corrected QT interval using Fredericia's formula (QTcF) >450 msec (as the mean of 3 consecutive readings 5 minutes apart) or history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, or family history of long QT syndrome)
- Major surgical procedure (including scoliosis surgery) planned within 1 year of the start of study treatment
- Poorly controlled asthma or underlying lung disease such as bronchitis, bronchiectasis, emphysema, recurrent pneumonia that in the opinion of the Investigator might impact respiratory function
- Platelets, white blood cells and/or haemoglobin < lower limit of normal (LLN) at screening (Note: for abnormal screening laboratory test results <LLN, the platelets count, white blood cell, and haemoglobin will be repeated once; if the repeat test result is still <LLN, the patient should be excluded)
- Fasting triglycerides >300 mg/dL (3.42 mmol/L) at screening (Note: if the value is >300 mg/dL, the triglycerides will be repeated once; if the repeated test result is still >300 mg/dL, the patient should be excluded)
- Current or history of liver disease or impairment, including but not limited to a baseline elevated total bilirubin (ie, >1.5 × upper limit of normal [ULN]), unless secondary to Gilbert disease or pattern consistent with Gilbert disease
- Inadequate renal function, as defined by serum Cystatin C result >2 × ULN (Note: if the value is >2 × ULN, the serum Cystatin C will be repeated once; if the repeated test result is still >2 × ULN, the patient should be excluded)
- Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
- Hypersensitivity to any component of study medication
- Sorbitol intolerance or malabsorption, or the hereditary form of fructose intolerance
- Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on Investigator judgement
- Psychiatric illness or social situations rendering the potential patient unable to understand and comply with the muscle function tests and/or with the study protocol procedures, based on Investigator judgement
- Have contraindications to Magnetic Resonance Imaging (MRI) scan (eg, claustrophobia, metal implants, or uncontrolled seizure disorder), based on Investigator's judgement.
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