NCT03805789终止2 期
A Phase 2/3, Multicenter, randOmized, Double-blind, Placebo-controlled, stUdy to evaLuate the Safety and Efficacy of Alpha-1 AntiTrypsin for the prEvention of Graft-versus-host Disease in Patients Receiving Hematopoietic Cell Transplant (MODULAATE Study)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- CSL Behring
- 入组人数
- 222
- 试验地点
- 68
- 主要终点
- The time to Grade II-IV aGVHD or death
研究概览
简要总结
This study is a phase 2 / 3 prospective, double-blind, randomized, multicenter, placebo-controlled study for prevention of acute GVHD (aGVHD) in participants undergoing an unrelated (matched or single allele mismatched) or matched related allogeneic hematopoietic cell transplantation (HCT). This study consisted of two parts. In Part 1, the dose of Alpha1-Proteinase Inhibitor (AAT) to be used in Part 2 was identified based on safety and pharmacokinetic data. The selected dose was subsequently evaluated in Part 2, where the primary objective was to assess its efficacy in preventing aGVHD following HCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •• Male or female participants, >=12 years of age (>= 18 years of age for participants at German sites only), undergoing HCT for hematological malignancies, including leukemia, lymphoma, multiple myeloma, myelodysplastic syndrome, and myeloproliferative neoplasms.
- •• Planned myeloablative conditioning regimen.
- •• Participants must have a related or unrelated donor as follows:
- •- Related donor must be a 6 / 6 match for human leukocyte antigen (HLA)-A, -B, at intermediate (or higher) resolution, and -DR beta 1 (DRB1) at high resolution using deoxyribonucleic acid (DNA)-based typing.
- •- Unrelated donor must be 7 / 8 or 8 / 8 match for HLA-A, -B, and -C at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing.
排除标准
- •• Prior autologous or allogeneic HCT.
- •• T cell depleted transplant or planned use of anti-T cell antibody therapy either ex vivo or in vivo (ie, anti thymocyte globulin [ATG], alemtuzumab) for GVHD prophylaxis.
- •• Planned umbilical cord blood transplant.
- •• Planned use of cyclophosphamide after HCT for GVHD prophylaxis.
- •• Planned haploidentical donor.
研究组 & 干预措施
AAT (low dose)
Experimental
Open label. AAT is a lyophilized product for intravenous (IV) administration
干预措施: AAT (Biological)
Placebo
Placebo Comparator
Albumin solution administered intravenously
干预措施: Placebo (Biological)
AAT (high dose)
Experimental
Open label. AAT is a lyophilized product for IV administration
干预措施: AAT (Biological)
AAT (selected dose from open-label)
Experimental
Double-blind. AAT is a lyophilized product for IV administration
干预措施: AAT (Biological)
AAT (medium dose)
Experimental
Open label. AAT is a lyophilized product for IV administration
干预措施: AAT (Biological)
结局指标
主要结局
The time to Grade II-IV aGVHD or death
时间窗: Through 180 days after HCT
Acute GVHD will be assessed using the Harris scoring system.
次要结局
- Proportion of participants with lower gastrointestinal (GI) aGVHD or Grade III-IV aGVHD in any organ(Through 180 days after HCT)
- Proportion of participants with severe infections defined by National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) greater than or equal to (>=) Grade 3(Through Day 60 after HCT)
- Proportion of participants with Grade II-IV aGVHD or death(Through 100 days and 180 days after HCT)
- Proportion of participants with lower GI aGVHD(Through Days 60, 100 and 180 after HCT)
- Proportion of participants with severe infections defined by NCI-CTCAE >= Grade 3(Through 100 and 180 days after HCT)
- Number of deaths (relapse and nonrelapse-related)(Within 180, 365, and 730 days after HCT)
- Proportion of participants with Grade III-IV aGVHD or death(Through Days 60, 100, and 180 days after HCT)
- Proportion of participants with moderate to severe chronic GVHD(Within 180, 365, 545, and 730 days after HCT)
- Proportion of participants who have discontinued immune suppression therapies including standard of care GVHD prophylaxis and steroid treatment(Within 180 and 365 days after HCT)
- Time to GVHD relapse-free survival(Within 365 and 730 days after HCT)
- Proportion of participants with relapse of primary malignancies(Through 180, 365, and 730 days after HCT)
- Time to neutrophil engraftment(Through 365 days after HCT)
- Proportion of participants with Grade II-IV aGVHD with an overall (complete + partial) response, complete response and partial response(Approximately 4 weeks after the initiation of systemic steroids during 8-week Treatment Period)
- Percent of participants with study drug related adverse events(Up to 365 days after HCT)
- Maximum concentration (Cmax) of AAT(Before and up to 72 after infusion of AAT)
- Area under the concentration curve (AUC) for AAT(Before and up to 72 after infusion of AAT)
- Ctrough of AAT(Before and up to 72 after infusion of AAT)
- Clearance (CL) of AAT(Before and up to 72 after infusion of AAT)
- Volume of distribution (V) for AAT(Before and up to 72 after infusion of AAT)
研究者
研究点 (68)
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