A Multicentre, Randomised, Double-blind, Placebo-controlled and Open Label Extension Study to Assess the Efficacy, Safety, and Pharmacokinetic Profile of of ATL1102 in Non-ambulatory Participants with Duchenne Muscular Dystrophy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 48
- 试验地点
- 13
- 主要终点
- Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 49 (combined treatment period).
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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 ≥
- •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.
排除标准
- •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
- •Exposure to more than 3 investigational products within the 12 months prior to Day
- •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
- •Has an increased risk for opportunistic infections or systemic medical conditions resulting in significantly compromised immune system function
研究组 & 干预措施
ATL1102 25mg
ATL1102 25mg administered subcutaneously once weekly
干预措施: ATL1102 25mg (Drug)
ATL1102 50mg
ATL1102 50mg administered subcutaneously once weekly
干预措施: ATL1102 50mg (Drug)
Placebo
Placebo is administered subcutaneously once weekly
干预措施: Placebo (Drug)
结局指标
主要结局
Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 49 (combined treatment period).
时间窗: 49 weeks
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
Change in the Performance of Upper Limb (PUL) 2.0 score from baseline to Week 25 (blinded treatment period).
时间窗: 25 weeks
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
Change in the Performance of Upper Limb (PUL) 2.0 score from Week 25 to Week 49 (open label treatment period).
时间窗: 49 weeks
The PUL is an assessment used to evaluate the upper limb strength for individuals with DMD where a higher score indicates a better outcome with a minimum of 0 and a maximum score of 42
Safety measured by the incidence and frequency of adverse events, serious adverse events and suspected unexpected adverse events from baseline to Week 65
时间窗: 65 weeks
An Adverse Event is any untoward medical occurrence in a participant and does not necessarily have to have a causal relationship with the intervention.
次要结局
- Change in the grip strength of the hand from baseline to Week 49 using a handheld dynamometer tool (MyoGrip) (combined treatment period).(49 weeks)
- Change in the respiratory function assessed by peak expiratory flow (PEF) from baseline to Week 49 (combined treatment period).(49 weeks)
- Change in the respiratory function assessed by Forced Vital Capacity (FVC) from baseline to Week 25 (blinded treatment period).(25 weeks)
- Safety measured by the incidence and frequency of adverse events, serious adverse events and suspected unexpected adverse events from baseline to Week 25 (blinded treatment period).(25 weeks)
- Time to Cmax and Cmin for ATL1102 over multiple timepoints(65 weeks)
- The terminal half life for ATL1102(65 weeks)
- Change in the grip strength of the hand from baseline to Week 25 using a handheld dynamometer tool (MyoGrip) (blinded treatment period).(25 weeks)
- Change in the pinch strength of the fingers from Week 25 to Week 49 using handheld dynamometer tool (MyoPinch) (open label treatment period).(49 weeks)
- Change in the respiratory function assessed by peak expiratory flow (PEF) from Week 25 to Week 49 (open label treatment period).(49 weeks)
- Change in the Paediatric Quality of Life (PedsQL) questionnaire Duchenne Muscular Dystrophy (DMD) Module from Week 25 to Week 49 (open label treatment period).(49 weeks)
- Change in the pinch strength of the fingers from Baseline to Week 49 using handheld dynamometer tool (MyoPinch) (combined treatment period).(49 weeks)
- Change in the respiratory function assessed by Forced Vital Capacity (FVC) from Baseline to Week 49 (combined treatment period).(49 weeks)
- Change in the Paediatric Quality of Life (PedsQL) questionnaire Duchenne Muscular Dystrophy (DMD) Module from Baseline to Week 49 (combined treatment period).(49 weeks)
- Change in the pinch strength of the fingers from baseline to Week 25 using handheld dynamometer tool (MyoPinch) (blinded treatment period).(25 weeks)
- Change in the respiratory function assessed by peak expiratory flow (PEF) from baseline to Week 25 (blinded treatment period).(25 weeks)
- Change in the Paediatric Quality of Life (PedsQL™) questionnaire Duchenne Muscular Dystrophy (DMD) Module from baseline to Week 25 (blinded treatment period).(25 weeks)
- Area under the plasma concentration time curve (AUC) for ATL1102 over multiple timepoints(65 weeks)
- Maximum and minimum plasma concentration (Cmax and Cmin) for ATL1102 over multiple timepoints(65 weeks)
- Change in the grip strength of the hand from Week 25 to Week 49 using a handheld dynamometer tool (MyoGrip) (open label treatment period).(49 weeks)
- Change in the respiratory function assessed by Forced Vital Capacity (FVC) from Week 25 to Week 49 (open label treatment period).(49 weeks)