A multicentre, randomised, double-blind, placebo-controlled and open label extension study to assess the efficacy, safety, and pharmacokinetic profile of two dose levels of ATL1102 administered by subcutaneous injection in nonambulatory participants with Duchenne Muscular Dystrophy

Prior treatment

• A participant who meets any of the following criteria will be excluded from participating in the study: 1.Participation in another clinical trial (non-interventional) or administration of any investigational product or experimental product within 12 weeks or 5 half-lives (whichever is longer) preceding Day 1.
• Received a live vaccine (including intranasal influenza vaccine) within 4 weeks prior to Day 1 or planned live vaccination during the study period.
• Planned or expected surgery during the study period (as judged by the Investigator).
• Chronic use (daily intake >14 days), within one month of Day 1, of beta-2 agonists or any use of other bronchodilating medication (e.g., inhaled steroids, sympathomimetics, anticholinergics).
• Exposure to more than 3 investigational products within the 12 months prior to Day 1.
• Currently receiving antiplatelet or anticoagulant therapy or has taken medication with an antiplatelet or anticoagulant effect within 4 weeks prior Day 1 (e.g., aspirin).

Other illness

• Known history of or a positive test for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibodies, human immunodeficiency virus (HIV) antibodies at Screening.
• Evidence of renal impairment and/or cystatin C >1.4 mg/L.
• Asthma (if requiring regular medication), bronchitis/chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, pneumonia or the presence of any non-DMD respiratory illness that affects PEF and FVC or other respiratory measures.
• Has an increased risk for opportunistic infections or systemic medical conditions resulting in significantly compromised immune system function (e.g., HIV, organ transplant, active malignancy).
• History of clinically significant bleeding or coagulation abnormalities.
• History of hypersensitivity to ATL1102 or to any of the excipients in the ATL1102 drug product formulation.

Lab values

• Used carnitine, creatine, glutamine, oxatomide, idebenone or other forms of coenzyme Q10 or vitamin E or any other nutritional or antioxidant supplements or herbal medicines or anabolic steroids other than standard corticosteroids or puberty testosterone supplementation within 4 weeks of Day 1. NOTE: daily multivitamin, Vitamin D or calcium supplements are permitted. Used ataluren, eteplirsen, casimersen, golodirsen (or other exon skipping antisense oligonucleotide drugs), and vamorolone within 6 months prior to Day 1. Used systemic immunosuppressants treatment (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, TNFɑ inhibitors) within the 3 months prior to Day 1. Used intravenous immunoglobulin (IVIg) within 6 months prior to Day 1. Refer Section 7.6.2 Prohibited Medication.
• Other than the condition under study, has a history of or current active medical condition including allergic, skin, cardiovascular, psychiatric disease, drug or alcohol abuse, severe behavioural or cognitive deficits, or laboratory finding, that in the opinion of the Investigator precludes participation in the study, or may interfere with the study objectives/results.
• Has the following abnormal haematology values during the Screening period: a.Lymphocytes <1.2 x 109/L b.Neutrophils <1.8 x 109/L c.Platelets <150 x 109/L.
• Has the following liver function test values during the Screening period: a.Gamma glutamyl transpeptidase (GGT) levels >2.0 x the upper limit of normal (ULN) or b.Total bilirubin concentrations greater than 1.5 x ULN or c. Glutamate dehydrogenase (GLDH) levels greater than 2.0 x ULN.
• Any evidence of clinically significant structural or functional heart abnormality (cardiomyopathy that is managed by ACEi or beta blockers is acceptable provided the LVEF inclusion criterion is met).

Other

• Requires day-time assisted mechanical or non-invasive ventilation (NIV) (night-time NIV is permitted).
• Unable to form a mouth seal to allow precise respiratory flow measurements and mouth pressure.
• An employee of the Sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, sibling, or child, whether biological or legally adopted.
• Clinically significant abnormal coagulation parameters.

• Has a parent/guardian who is capable of understanding the purposes and risks of the study and is able to provide voluntary written informed consent for the participant to participate in the study and assent will be documented.
• Has adequate cardiac function defined as left ventricular ejection fraction (LVEF) ≥45% by echocardiogram and if receiving cardiac medication, must be currently on a stable regimen and doses of cardiac therapy (at least 3 months prior to baseline Day 1) including angiotensin converting enzyme inhibitors (ACEi), angiotensin 2 receptor antagonists (A2RA), aldosterone receptor antagonists (ARA) or beta blockers (BB).
• Participant who is post pubertal and sexually active must agree to use approved methods of contraception (condoms or abstinence) for the duration of the study and until 4 months after administration of the last dose of the study medication. Female sexual partner must also agree to use a medically acceptable form of contraception.
• Participant and their parent/guardian are willing and able to comply with scheduled visits, study medication administration and study procedures.
• Where required by law or if the Investigator determines the potential participant is of sufficient maturity and has the ability to understand the nature and consequence of the study, participant consent will be obtained. Otherwise, assent will be documented.
• Has a clinical diagnosis of DMD confirmed by validated genetic testing (i.e., documented deletion, duplication or point mutation in the dystrophin gene).
• Is considered to be non-ambulatory, defined as unable to walk 10 meters without assistance or help at Screening
• Male aged 10 to less than 18 years, at the time of screening and informed consent for participation in the study.
• Body weight of at least 25 kg at Screening.
• If receiving corticosteroid therapy, therapy was initiated at least six months prior to the baseline visit and a stable daily dose for at least 3 months prior to baseline and, there is currently no clinical intent to alter the dose during the study period, except for adaption for body weight.
• On study entry (Screening and Baseline), the participant has a Performance of Upper Limb Module for DMD 2.0 (PUL 2.0) Entry Item A score ≥2.
• Able to perform spirometry and has sufficient Respiratory function defined as reproducible percent predicted FVC ≥50%. Ability to provide reliable and reproducible repeat FVC with the best of three attempts assessed at Baseline being within 20% of the best of three attempts assessed at Screening.