A Phase 2 Double-Blinded, Randomized, Placebo-Controlled Study to Assess the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Intravenous Administration of ARGX-119 in Pediatric Participants Aged 5 to Less Than 18 Years With Spinal Muscular Atrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- argenx
- 入组人数
- 60
- 试验地点
- 29
- 主要终点
- Incidence of AEs
研究概览
简要总结
This study aims to find the correct dose of ARGX-119 for children with SMA. The study will also look at how safe the study drug is, how well it works, how it moves through the body, and how the immune system responds to it. The study consists of a double-blinded treatment period (DBTP) where participants will either receive ARGX-119 IV or placebo IV, in addition to disease-modifying therapy (DMT) for 24 weeks. Participants who complete the DBTP will enter the open-label active-treatment extension period (ATEP) during which all participants will receive ARGX-119 IV up to 100 weeks (approximately 2 years).
详细描述
This phase 2 study aims to establish proof of concept with the age-appropriate dose of ARGX-119 in ambulant pediatric patients with spinal muscular atrophy (SMA). Despite available treatments, there remains an unmet medical need for patients with SMA. Neuromuscular junction (NMJ) dysfunction contributes to the pathophysiology of SMA, including muscle weakness and fatigability. Activation of muscle-specific kinase (MuSK) by ARGX-119 may stabilize and improve NMJ function in patients with SMA, reducing muscle weakness and fatigability, and improving quality of life.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is aged ≥5 to <18 years when completing the informed consent process, defined as providing informed assent according to local regulations and having a parent or guardian sign the ICF, and can comply with protocol
- •requirements.
- •Has documented historical genetic diagnosis of 5q-SMA.
- •Currently receiving a stable SMA treatment regimen (nusinersen or risdiplam) and/or have a history of onasemnogene abeparvovec treatment
- •Must be able to walk at least 50 meters without walking aids in the 6MWT at screening
排除标准
- •Known medical condition that would interfere with an accurate assessment of SMA, confound the results of the study, or put the participant at undue risk, as assessed by the investigator
- •Recent major surgery, except spinal fusion, within 3 months of screening or intends to have major surgery during the study
- •Current or previous administration of antimyostatin therapies in the past 6 months
- •Severe scoliosis (defined as curvature >40°) and/or contractures at screening. o History of spinal fusion within 6 months before screening or planned during the study
- •Respiratory insufficiency, defined by the medical necessity for invasive or noninvasive ventilation for daytime treatment while awake. Ventilation used overnight or during daytime naps is acceptable.
研究组 & 干预措施
ATEP - ARGX-119 IV
Participants receive ARGX-119 IV during the ATEP. Participants from ARGX-119 IV arm in the DBTP will receive placebo once to maintain the DBTP blinding
干预措施: ARGX-119 IV (Biological)
ATEP - ARGX-119 IV
Participants receive ARGX-119 IV during the ATEP. Participants from ARGX-119 IV arm in the DBTP will receive placebo once to maintain the DBTP blinding
干预措施: Placebo IV (Other)
DBTP - ARGX-119 IV
Participants receive ARGX-119 IV during the DBTP
干预措施: ARGX-119 IV (Biological)
DBTP - Placebo IV
Participants receive placebo IV during the DBTP
干预措施: Placebo IV (Other)
结局指标
主要结局
Incidence of AEs
时间窗: Up to 124 weeks
Adverse Events
Incidence of SAEs
时间窗: Up to 124 weeks
Serious Adverse Events
Change in RHS total score from baseline to week 24 of the double blinded treatment period (DBTP)
时间窗: Up to 24 weeks
The RHS (Revised Hammersmith Scale) is a validated 36-item scale developed to evaluate the spectrum of gross motor function. Maximum total score; 69 (optimal motor function)
次要结局
- Change from baseline over time for the 6MWT - distance and fatigue index(Up to 124 weeks)
- ARGX-119 serum concentrations over time(Up to 124 weeks)
- Incidence of antidrug antibodies (ADA) against ARGX-119(Up to 124 weeks)