Inhaled Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) in Hereditary Pulmonary Alveolar Proteinosis (PAP)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Change in Time (Minutes) to Discontinuation of Exercise During a Standardized Treadmill Exercise Test
研究概览
简要总结
The purpose of this study is to evaluate the therapeutic efficacy of inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (PAP) due to partial dysfunction of the GM-CSF receptor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 8 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A diagnosis of PAP caused by bi-allelic mutations in CSF2RA or CSF2RB associated with impaired GM-CSF-R-alpha or GM-CSF-R-beta function, respectively, resulting in reduced but non-zero GM-CSF signaling
- •Able and willing to give written informed consent / assent as necessary
- •Clinically stable
排除标准
- •Confirmed diagnosis of a disorder of surfactant production caused by bi-allelic mutations in ABCA3, SFTPB, or SFTPC
- •Confirmed diagnosis of autoimmune PAP caused by a high level of GM-CSF autoantibody
- •Confirmed diagnosis of secondary PAP caused by an underlying clinical disorder known to be associated with the development of PAP, e.g., inhalation of silica or titanium; myelodysplasia and others
- •Treatment with any investigational agent in the 3 months prior to enrollment
- •History of severe allergic or anaphylactic reactions to GM-CSF or other yeast-derived products
- •History of asthma or other reactive airways disease
- •Known active, viral, fungal, mycobacterial, or other infection
- •A serious medical condition which, in the opinion of the investigator or data and safety monitoring committee, would make the patient unsuitable for the study
研究组 & 干预措施
Inhaled Leukine (rhGM-CSF)
Inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (hPAP) due to partial dysfunction of the GM-CSF receptor
干预措施: Leukine (Drug)
结局指标
主要结局
Change in Time (Minutes) to Discontinuation of Exercise During a Standardized Treadmill Exercise Test
时间窗: Baseline, 7 months
A modified Bruce protocol stress test was used to evaluate improvement in blood oxygen saturation (SpO2). A pulse-oximeter was placed on the participant's finger with the participant at rest while sitting in a chair. Leads for the electrocardiograph were placed on the chest wall. The treadmill was started at 1.7 miles per hour (mph) and a grade of 0%. At three minute intervals, the speed increased as follows: 1.7 mph, 1.7 mph, 1.7 mph, 2.5 mph, 3.4 mph, 4.2 mph, 5.0 mph, 5.5 mph, 6.0 mph, 6.5 mph, 7.0 mph, and 7.5 mph. The participant stopped the test due to intolerable dyspnea or if the SpO2 fell below 88%.
Change in Minimum Pulse Oximetry During a Standardized Treadmill Exercise Test
时间窗: Baseline, 7 months
A modified Bruce protocol stress test was used to evaluate improvement in blood oxygen saturation (SpO2). A pulse-oximeter was placed on the participant's finger with the participant at rest while sitting in a chair. Leads for the electrocardiograph were placed on the chest wall. The treadmill was started at 1.7 miles per hour (mph) and a grade of 0%. At three minute intervals, the speed increased as follows: 1.7 mph, 1.7 mph, 1.7 mph, 2.5 mph, 3.4 mph, 4.2 mph, 5.0 mph, 5.5 mph, 6.0 mph, 6.5 mph, 7.0 mph, and 7.5 mph. The participant stopped the test due to intolerable dyspnea or if the SpO2 fell below 88%.
次要结局
- Change in Diffusion Capacity for Carbon Monoxide(Baseline, 7 months)
- Change in Minimum Pulse Oximetry During a Standardized Exercise Protocol Oximetry(Baseline, 7 months)
- Change in Radiographic Evidence of PAP Lung Disease(Baseline, 7 months)
- Change in Quality of Life(Baseline, 7 months)
- Change in Dyspnea Symptom Score(Baseline, 7 months)
- Change in Serum Anti-GM-CSF Antibodies Levels(Baseline and monthly up to 7 months)
- Change in Serum Biomarkers - GM-CSF(Baseline and monthly up to 7 months)
- Change in Serum Biomarkers - Surfactant Protein D(Baseline and monthly up to 7 months)