a study of atl1102 or placebo in participants with non-ambulatory duchenne muscular dystrophy

Conditions: Duchenne Muscular Dystrophy

Summary: this phase iib study is a two part, multicenter study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of atl1102 in non-ambulant boys with duchenne muscular dystrophy aged 10 to \<18 years old. the study includes a randomised, double-blind, placebo-controlled treatment period (part a), followed by an open labelled treatment period (part b).

this phase iib study is a two part, multicenter study to evaluate the efficacy, safety, pharmacokinetics and pharmacodynamics of atl1102 and will enroll 45 non-ambulant boys with duchenne muscular dystrophy (dmd) aged 10 to \<18 years old. during the 24 week randomised, double-blind, placebo-controlled treatment period (part a) participants will be enrolled and randomised to receive either atl1102 25mg, atl1102 50mg or matched placebo in a 1:1:1 ratio given as a weekly subcutaneous injection. participants will then continue to the 24 week open labelled treatment period (part b) and continue to receive atl1102 25mg or atl1102 50mg for a further 24 weeks. participants on placebo in part a will transition to atl1102. the study will consist of a 4 week screening period, 24 week randomised, double-blind, placebo-controlled treatment period (part a), 24 week open label treatment period (part b) and 16 week follow up period.

Eligibility criteria:
key inclusion criteria: * has a clinical diagnosis of dmd confirmed by validated genetic testing * 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. * 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 * 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%. * 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) * participant and their parent/guardian/carer are willing and able to comply with scheduled visits, study medication administration and study procedures. key exclusion criteria: * 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. * exposure to more than 3 investigational products within the 12 months prior to day 1. * history of clinically significant bleeding or coagulation abnormalities or clinically significant abnormal coagulation parameters. * currently receiving antiplatelet or anticoagulant therapy or has taken medication with an antiplatelet or anticoagulant effect within 4 weeks prior day 1 * 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). * 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. * received a live vaccine (including intranasal influenza vaccine) within 4 weeks prior to day 1 or planned live vaccination during the study period. * 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. * requires day-time assisted mechanical or non-invasive ventilation (niv) (night time niv is permitted). * 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). * 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. * has an increased risk for opportunistic infections or systemic medical conditions resulting in significantly compromised immune system function

Keywords: non-ambulatory dmd