Phase 1/2a study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of SQY51 in Paediatric and Adult Patients with a Genetically Confirmed Diagnosis of Duchenne Muscular Dystrophy

Prior treatment

• Patient who participated in other investigational study within the last three months, including those with investigational drugs that aim at restoring dystrophin expression such as other antisense oligomers.
• Patient that received gene therapy.
• Patient for whom major orthopedic surgery is planned during the phase 1 of the study (little invasive procedures such as tenotomy are permissible during phase 2, any procedure is permissible during the extension phase).
• Tracheostomized patients and dependent on invasive mechanical ventilation. Non-invasive mechanical ventilation ≥ 16 h/day. Medical history with more than two respiratory decompensations requiring hospitalization during the previous year. No respiratory decompensation in the four months preceding enrolment.
• Patients on medications that can restore dystrophin expression, tamoxifen and other drugs without indication for DMD or pediatric population.

Other illness

• Patient with any serious medical/surgical or psychiatric condition/illness/history that in the opinion of the investigator would jeopardize patient’s safety or would interfere with the study assessments/results, including insufficient obligatory vaccination against infectious diseases as recommended by national guidelines, medical history of infection with Hepatitis B,C and HIV
• Patient with a history of significant allergic reactions and with any known allergies to products likely to be used in the study (e.g., antiseptics, anaesthetics), known hypersensitivity to any of the ingredients, or excipients of the study drug.

Lab values

• Abnormal laboratory values in the clinically significant range
• Patient with advanced cardiomyopathy and LVEF <40%. Patients with dysrhythmias and being treated for dysrhythmias. Patients with nontreated tachycardia.

Other

• Patient with intellectual disability or behavioral problem such that they cannot comply with the study procedure.

• Boys ≥6 years of age and ≥16 kg body weight.
• Concomitant regular treatment with corticosteroids (Prednisone or Deflazacort on daily, alternative or intermittent dosing) for at least three months prior enrolment. Corticosteroid treatment is expected to remain stable during the study, however, can be dose/drug adapted according to weight change of patients.
• If clinically indicated, approved concomitant treatment within standards of care guidelines for DMD, such as antihypertensive, vasodilators, lipid-lowering, thyroid replacement, vitamins, mineral substitution, gastric protectors, nutritional supplements. Patients on the therapies are eligible only if they are on a stable dose for at least one month prior to enrolment until completion of part 2. These treatments can be initiated or adapted as clinically indicated throughout the study.
• Non-invasive mechanical nocturnal ventilation is permissive if <16 h/day.
• For the extension phase : Patients must have completed Phase 2a of the study.
• Being affiliated with a Social Security.
• Informed consent form signed by the patient or, if minor, by the legal guardian(s).
• For phase 2a study: Must have completed Phase 1 of the study.
• Ambulatory or non-ambulatory status, described as Ambulatory stage: Able to rise from the floor and able to walk 10 m without assistance (inclusion of at least 4 patients). Early non-ambulatory stage: Unable to walk 10 m without assistance, including human assistance. Loss of ambulation (LoA) ≤ 5 years preceding enrolment (inclusion of maximal 8 patients). Late non-ambulatory stage: LoA > 5 years preceding enrolment (inclusion of maximal 3 patients).
• Patients and, if minor, their legal guardians who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Diagnosed with DMD, genotypically confirmed with DMD mutations amenable to exon-51 skipping.
• Stable hepatic and renal function: • GGT <1.5×ULN, AST <25×ULN, ALT <15×ULN • Total bilirubin <1.5×ULN. • Alkaline phosphatase ≤1.5×ULN. • Estimated glomerular filtration rate ≥90 mL/min/1.73m2. • Proteinuria and microalbuminuria ≤ULN.
• Echocardiography left ventricular ejection fraction (LVEF) at screening ≥40%.