Phase 1/2 Study of the Effect of Adalimumab on Physical Function and Musculoskeletal Disease in Mucopolysaccharidosis Types I, II, and VI
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Pain - 16 weeks
研究概览
简要总结
Randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI.
详细描述
This study is a randomized, double-blind, placebo-controlled, parallel-group, single-center study followed by open-label phase, to evaluate the effects of adalimumab compared to placebo on the change from baseline in joint and skeletal disease in children and adults with mucopolysaccharidosis (MPS) I, II or VI. Children and adults diagnosed with MPS I, II or VI, with significant joint restrictions and pain will be randomized to adalimumab treatment or placebo treatment for the first 16 weeks. This will be followed by a 32-week open label adalimumab treatment phase.
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
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥5 years of age;
- •Diagnosis of MPS I, II or VI;
- •Treatment with ERT for ≥1 year or no treatment with ERT for ≥1 year;
- •Weight ≥15 kg;
- •Significant bodily pain reported by the CHQ-PF50 or SF-36 (> 1 SD more severe [below] than the general population mean);
- •≥ 3 joints with limitations in motion; and Patient or parent/legal guardian is able and willing to provide informed consent. For patients 7 to 17 years of age, assent must also be provided.
排除标准
- •History of HCT less than 2 years prior to enrollment;
- •Immune suppression therapy less than 1 year prior to enrollment;
- •Active graft versus host disease;
- •Current diagnosis or history of lymphoma or other malignancy;
- •Current active infection;
- •History of serious opportunistic infection (e.g., bacterial [Legionella and Listeria]; tuberculosis [TB]; invasive fungal infections; or viral, parasitic, and other opportunistic infections);
- •Positive TB skin test, positive Quantiferon-TB Gold TB test, positive chest X-ray, or a recent exposure to TB
- •Congestive heart failure defined by an ejection fracture <50% measured by ECHO;
- •Demyelinating disorders (e.g., central nervous system [CNS] disorders including multiple sclerosis and optic neuritis and peripheral nervous system disorders including Guillain-Barre syndrome);
- •Hematologic abnormalities (e.g., pancytopenia, aplastic anemia);
- •Hepatitis B infection (active or chronic carrier);
- •Latex sensitivity;
- •Pregnancy or breastfeeding;
- •Known or suspected allergy to adalimumab or related products;
- •Participation in simultaneous therapeutic study that involves an investigational study drug or agent within 4 weeks of study enrollment;
- •Requirement for live vaccine exposure that would be expected to occur during the time frame of the study; or
- •Any other social or medical condition that the Investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated or be detrimental to the study.
研究组 & 干预措施
Adalimumab
20 mg subQ every other week (weight 15to <30 kg) 40 mg subQ every other week (weight ≥30 kg). Non-responders will be escalated to weekly dosing.
干预措施: Adalimumab Injection [Humira] (Drug)
Placebo
Saline placebo comparator
干预措施: Saline Solution for Injection (Drug)
Open-label adalimumab
Open-label extension of adalimumab dose
干预措施: Adalimumab Injection [Humira] (Drug)
结局指标
主要结局
Pain - 16 weeks
时间窗: 16 weeks
Mean difference in bodily pain measured by the Children's Health Questionnaire - Parent Form 50 (CHQ-PF50) or the Medical Outcomes Study - Short Form 36 (SF-36) in treatment versus placebo at 16 weeks
Adalimumab trough
时间窗: 32 weeks
Percentage of subjects who achieve a goal trough concentration of adalimumab with every other week dosing
次要结局
- Pain - 52 weeks(52 weeks)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability(52 weeks)
- Joint range-of-motion - 16 weeks(16 weeks)
- Joint range-of-motion - 52 weeks(52 weeks)
研究者
Lynda E Polgreen
Principal Investigator
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center