An Open-label Phase IIa Study to Evaluate the Safety and Preliminary Efficacy of HBMMSC Injection in the Treatment of APAP
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Alveolar-arterial difference in oxygen tension (A-aDO2)
研究概览
简要总结
The purpose of this open-label phase IIa clinical trial study is to evaluate the safety and preliminary efficacy of hBMMSC intravenous treatment in patients with aPAP.
详细描述
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare lung disease for which there is no specific drug treatment. Currently, the standard treatment strategy for PAP is whole-lung lavage (WLL), which is invasive and has limited therapeutic efficacy. The purpose of this study is to evaluate the safety and preliminary efficacy of hBMMSC intravenous treatment in patients with aPAP. The clinical trial intends to involve 10 participants. The trial is expected to last approximately 2 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 years or older
- •Patients diagnosed with aPAP by both CT and biopsy (TBLB, TBCB, or surgical lung biopsy) or bronchoalveolar perfusion (BAL) as well as GM-CSF autoantibodies in serum positive
- •No remission was demonstrated by CT, pulmonary function test results,or blood gas analysis at least 2 times (at least 3 months apart) before enrollment
- •At rest PaO2≤70 mmHg
- •Fertile participants must receive effective medical contraception (for both male and female participants, up to one year after the last study dosing)
- •Voluntary signed informed consent
排除标准
- •Diagnosed with hereditary PAP, secondary PAP, or another type of PAP
- •Received whole lung lavage（WLL） therapy within 6 months before enrollment
- •Received previous GM-CSF therapy within 6 months before enrollment
- •Received other clinical trial treatment within 3 months before enrollment
- •Participated in other stem cell studies within 1 year before enrollment
- •Inflammatory disease or autoimmune disorder requiring treatment associated with significant immunosuppression (e.g. more than 10 mg/day systemic prednisolone)
- •Active infection (viral, bacterial, fungal or mycobacterial), which may affect the assessment of efficacy in the trial
- •History of malignant tumors
- •Known allergic reactions to any of the ingredients in the study drug
- •Participants who, in the opinion of the investigator, would aggravate any other serious pre-existing medical condition are not suitable for this trial
- •Women who are known to be pregnant, breastfeeding, have a positive pregnancy test (which will be detected during the screening process), or plan to become pregnant during the trial
研究组 & 干预措施
Experimental: hBMMSC
1.0×10^6/kg hBMMSC (participant's body weight) single dose 2.0×10^6/kg hBMMSC (participant's body weight) single dose 2.0×10^6/kg hBMMSC (participant's body weight) administered twice
干预措施: human Bone Marrow Mesenchymal Stem Cell (hBMMSC) (Drug)
结局指标
主要结局
Alveolar-arterial difference in oxygen tension (A-aDO2)
时间窗: 24 weeks
The changes of alveolar-arterial difference in oxygen tension (A-aDO2) relative to baseline were assessed in the hBMMSC treated group after 24 weeks of treatment.
次要结局
- Imaging（Chest CT score ）(24 weeks, 48 weeks)
- Safety and tolerability(48 weeks)
- Difference in pulmonary function(4 weeks, 12 weeks, 24 weeks, 48 weeks)
- Alveolar-arterial oxygen difference (A-aDO2)(48 weeks)
- Difference in 6-minute walk distance (6MWD)(4 weeks, 12 weeks, 24 weeks, 48 weeks)
- Percutaneous arterial oxygen saturation (SpO2)(4 weeks, 12 weeks, 24 weeks, 48 weeks)
- Difference in modified Medical Research Council（mMRC）(4 weeks, 12 weeks, 24 weeks, 48 weeks)
- Difference in St. George's Respiratory Questionnaire（SGRQ）(4 weeks, 12 weeks, 24 weeks, 48 weeks)
- Difference in Disease severity score (DSS)(24 weeks, 48 weeks)
- Difference in arterial partial pressure of oxygen (PaO2)(24 weeks, 48 weeks)
- Difference in Krebs Von den Lungen-6（KL-6）(2 weeks，4 weeks, 12 weeks, 24 weeks)
- Difference in carcinoembryonic antigen（CEA）(2 weeks，4 weeks, 12 weeks, 24 weeks)
- Difference in lactate dehydrogenase (LDH)(2 weeks，4 weeks, 12 weeks, 24 weeks)
- Number of Rescue whole lung lavage (WLL) in 108 weeks(108 weeks)