Phase 2 Randomised Controlled Trial of Bone-marrow Derived Mesenchymal Stromal Cells (MSC) for New Onset Chronic Lung Allograft Dysfunction (CLAD)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 5
- 主要终点
- Progression-free survival
研究概览
简要总结
This study is designed for lung transplant patients who have developed chronic lung allograft dysfunction (CLAD). Consented patients will receive 4 intravenous doses of allogeneic, bone-marrow-derived MSCs (2*10^6 cells/kg/dose) or matching placebo over a period of 2 weeks with a 12 month follow up.
详细描述
This is a phase 2, multi-center, randomized study (n=82, 1:1 MSC:placebo) where consented patients will receive 4 intravenous doses of IMP over a period of 2 weeks. Patients must provide written informed consent and meet the all Inclusion Criteria and none of the Exclusion Criteria to be eligible. Screening procedures include obtaining medical history, current medications, questionnaires, vital signs, Chest Xray, 6 Minute walk test and blood tests. Historical chest CT and full lung function from 12 weeks prior to screening may be used. Bronchoscopy with biopsy must have been performed no more than 6 months prior to screening. A bronchoscopy with bronchoalveolar lavage (BAL) is required, however will not need to be repeated if performed within 14 days prior to the baseline visit. Patients will then receive 4 infusions of MSC/placebo over a period of 2 weeks, with follow up at Week 3,6,10,14,28,41 and week 54.
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
- Triple (Participant, Care Provider, Investigator)
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
- •Bilateral lung transplant recipients aged ≥ 18 years and at least 6 months post-transplant. Patients with other organs transplanted (eg heart, liver, kidney) or those who have undergone lobar transplantation, or re-transplantation, are potentially eligible.
- •New-onset CLAD (defined as a persistent (3weeks apart) fall in FEV1 of at least 20% from the mean of the two best post-transplant values taken at least 3 weeks apart) in the 12 months prior to the screening visit. Other causes of a fall in FEV1 (acute cellular or humoral rejection, active infection, anastomotic stenosis etc.) must be excluded as per international guidelines.
- •Stable immunosuppression regimen, as assessed by the investigator, in the 8 weeks prior to the screening visit.
- •Available for all specified assessments at the study site through the completion of the study, including the protocol bronchoscopies.
- •Provision of written informed consent.
排除标准
- •Any condition that in the opinion of the Investigator may interfere with the safety of the patient, his / her completion of required follow-up visits or evaluation of the study objectives
- •Untreated cellular or humoral rejection
- •Clinically meaningful and untreated viral, bacterial or fungal infection
- •Use of azithromycin or another macrolide antibiotic, if commenced within 8 weeks of the screening visit
- •Intravenous pulsed methylprednisolone, within 4 weeks of the screening visit
- •Use of extracorporeal photopheresis, within 4 weeks of the screening visit
- •Use of total lymphoid irradiation, within 4 weeks of the screening visit
- •Poor functional status not expected to survive 6 months
- •Allergy to beef products
- •Women who are pregnant, breast-feeding or unwilling to use adequate contraception
- •Patients who are currently participating in another interventional clinical trial
研究组 & 干预措施
Bone-marrow derived MSCs
4 doses of Allogeneic bone-marrow derived MSCs (2x106 cells/kg) given intravenously twice weekly for 2 weeks
干预措施: Bone-marrow derived MSCs (Drug)
Placebo
Placebo product manufactured to look like MSCs
干预措施: Placebo (Drug)
结局指标
主要结局
Progression-free survival
时间窗: From baseline to week 54
Progression-free survival is a composite end-point of freedom from CLAD progression or death from any-cause. CLAD progression is defined as fall in FEV1 \> 10% from the baseline (screening visit) FEV1 to the 12 month (week 54) visit.
次要结局
- Time to fall in FEV1 > 10%(From the baseline (screening) visit)
- Freedom from Bronchiolitis Obliterans Syndrome (BOS) grade 3(Week 54)
- All cause mortality(Week 54)
- CLAD-specific mortality(Week 54)
- Freedom from acute rejection(From baseline to week 54)
- Freedom from the development of new donor specific anti-HLA antibodies(From baseline to week 14)
- Freedom from CLAD progression(From baseline to week 54)
- Rate of FEV1 decline(From baseline to week 54)
- Rate of FVC decline(From baseline to week 54)
- Change in 6-minute walk distance (6MWD)(From baseline to week 54)
- Change in St George's Respiratory Questionnaire (SGRQ) Score(From baseline to week 54)
- Inpatient bed-days(From baseline to week 54)
研究者
Daniel Chambers
A/Prof Daniel Chambers
The University of Queensland