Efficacy, Safety and Tolerability of Givinostat in Non-ambulant Patients With Duchenne Muscular Dystrophy

Launched by ITALFARMACO · Jun 27, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a medication called givinostat to see if it is effective and safe for boys aged 9 to under 18 who have Duchenne Muscular Dystrophy (DMD) and are unable to walk (non-ambulant). The study will include 138 participants who will be divided into two groups: one will receive givinostat, and the other will receive a placebo (a treatment that looks like the real medication but has no active ingredient). The trial will last for about 18 months, during which researchers will monitor how well the medication works and how well the participants tolerate it.

To be eligible for the trial, boys must be diagnosed with DMD, unable to walk independently, and meet other specific health criteria. For example, they must be stable on certain medications for their heart and have no major health issues that could interfere with the study. Participants will undergo screening for about four weeks before the treatment starts, followed by the 18-month treatment phase and a follow-up period. This study is currently recruiting participants, and caregivers can expect regular health checks and assessments during the trial to ensure the safety and well-being of their child.

Gender

MALE

Eligibility criteria

• Inclusion Criteria:
• Patients must satisfy all the following criteria:
• • 1. 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)
• • 2. Are able to give informed assent and/or consent in writing signed by the patient and/or parent/legal guardian (according to local regulations)
• • 3. A genetic diagnosis of DMD
• 4. Non-ambulant, defined as being wheelchair bound and:
• • 1. Unable to perform the 10-meter walk/run test (10MWT), or
• • 2. Unable to complete the 10MWT in 30 seconds or less, without any support or devices
• • 5. Performance of the Upper Limb test (PUL version 2.0) entry item scores 3 to 6
• • 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
• 7. Stable corticosteroids, defined as:
• • 1. Receiving systemic corticosteroids for a minimum of 6 months immediately prior to start of study treatment
• • 2. 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
• 8. Willing to use adequate contraception. Effective contraceptive methods must be used from randomisation visit through 3 months after the last dose of study drug, and include the following:
• • 1. True abstinence (ie, absence of any sexual intercourse), when in line with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation, post-ovulation, and symptothermal methods) and withdrawal are not acceptable methods of contraception
• • 2. Condom with spermicide and the female partner must use an effective method of contraception, such as an oral, transdermal, injectable or implanted hormonal contraceptive; intrauterine device; bilateral tubal occlusion, or a diaphragm or a barrier method of contraception in conjunction with spermicidal jelly such as for example cervical cap with spermicide jelly.
• Exclusion Criteria:
• Patients will be excluded from the study if they satisfy any of the following criteria:
• • 1. Exposure to another investigational drug within 3 months prior to start of study treatment.
• • 2. Have exposure to any dystrophin restoration product (eg, Ataluren, Exon skipping) within 6 months prior to the start of study treatment
• • 3. Having received any gene therapy (eg, AAV Micro-dystrophin delivery) prior to start of study treatment
• • 4. 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
• • 5. 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
• • 6. Elbow-flexion contractures \>30° in the dominant arm
• • 7. 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
• • 8. Forced Vital Capacity % of predicted \<40%
• • 9. Requirement for daytime ventilator assistance (Note: Night ventilator assistance and use of bi-level positive airway pressure therapy is allowed)
• • 10. Episode of respiratory failure within the 8 weeks prior to screening
• • 11. Symptomatic cardiomyopathy or heart failure and/or left ventricular ejection fraction \<45%
• • 12. 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)
• • 13. Major surgical procedure (including scoliosis surgery) planned within 1 year of the start of study treatment
• • 14. 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
• • 15. 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)
• • 16. 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)
• • 17. 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
• • 18. 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)
• • 19. Positive test for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus at screening
• • 20. Hypersensitivity to any component of study medication
• • 21. Sorbitol intolerance or malabsorption, or have the hereditary form of fructose intolerance
• • 22. Diagnosis of other uncontrolled neurological diseases or presence of relevant uncontrolled somatic disorders that are not related to DMD, based on Investigator judgement
• • 23. 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
• • 24. Have contraindications to MRI scan (eg, claustrophobia, metal implants, or uncontrolled seizure disorder), based on Investigator's judgement.