NCT04227938终止1 期
An Open-label Study of ALPN-101 in Steroid-resistant or Steroid-refractory Acute Graft Versus Host Disease (aGVHD)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 4
- 主要终点
- Adverse events
研究概览
简要总结
The Balance study will assess the safety, tolerability, and efficacy of an investigational drug called ALPN-101 in adults with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).
详细描述
AIS-A02 is a Phase 1b open-label study of ALPN-101 administered to adult subjects with steroid-resistant or steroid-refractory acute graft versus host disease (aGVHD).
It will be conducted at approximately 10 US sites. Up to 72 subjects will be enrolled in Part A (dose escalation) and up to 25 subjects will be enrolled in Part B (dose expansion).
In each Part, safety and efficacy assessments will be performed throughout the dosing and follow-up periods, and multiple PK and PD samples will be collected.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Status post first allogeneic stem cell transplantation (allo-SCT) from any donor source using any conditioning regimen.
- •Grade Ⅱ-Ⅳ acute GVHD per Mount Sinai Acute GVHD international Consortium (MAGIC) criteria.
- •Corticosteroid resistant or refractory as defined as any of the following:
- •Progression of aGVHD within 5 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent;
- •Failure to improve within 7 days following initiation of treatment with ≥ 2 mg/kg/day of prednisone or equivalent; or
- •Incomplete response (failure to achieve Complete Response) after 28 days of immunosuppressive treatment including steroids (treatment with ≥ 2 mg/kg/day of prednisone or equivalent).
- •Must agree to use appropriate contraception.
- •Female subjects must not be pregnant or breastfeeding.
- •In addition, the following criteria must be met prior to dosing with ALPN-101 on Day 1:
- •Karnofsky performance score ≥
- •No evidence of an active, uncontrolled bacterial, viral, or fungal infection.
排除标准
- •Current veno-occlusive disease, or current treatment with dialysis or mechanical ventilation associated with GVHD.
- •Prior donor lymphocyte infusion (DLI).
- •Receipt of any live vaccine within 4 weeks of ALPN-101 dosing.
- •Presence of any active malignant disease.
- •Corticosteroid therapy at doses > 1 mg/kg/day prednisone or equivalent for indications other than GVHD ≤ 7 days p ALPN-101 dosing.
- •Treatment with any of the following ≤ 2 weeks prior to ALPN-101 dosing: targeted inhibitors of the CD28/CD80/86 pathway (e.g. abatacept, belatacept), targeted inhibitors of the ICOS/ICOSL pathway
- •Initiation of treatment with salvage therapy < 2 days prior to ALPN-101 dosing. Concurrent salvage therapy that is intended to be continued must be at a stable dose for ≥ 2 days prior to ALPN-101 dosing.
- •Treatment for aGVHD with adoptive cell therapy, investigational agents, devices, or procedures ≤ 2 weeks or 5 half-lives-whichever is greater-prior to ALPN-101 dosing, unless approved by the medical monitor and sponsor; prior treatment with mesenchymal stem cells is permitted.
- •Known allergies, hypersensitivity, or intolerance to study drug, excipients, or similar compounds.
- •Any medical complications or conditions that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data.
研究组 & 干预措施
ALPN-101
Experimental
All subjects will receive a single dose of ALPN-101. In Part A, ascending dose levels of ALPN-101 will be evaluated. In Part B, a single dose level of ALPN-101-as identified in Part A-will be evaluated.
干预措施: ALPN-101 (Drug)
结局指标
主要结局
Adverse events
时间窗: From study Day 1 (dosing of ALPN-101) until Day 29
The incidence, severity, and seriousness of AEs, including dose-limiting toxicities, assessed by CTCAE
次要结局
- Malignancy relapse/progression (MR)(From study Day 1 (dosing of ALPN-101) until the date of relapse/progression of the primary malignancy, assessed up to 36 months)
- Non-relapse mortality (NRM)(From study Day 1 (dosing of ALPN-101) until progression or death due to any cause without prior progression, assessed up to 36 months)
- Objective Response Rate (ORR)(From study Day 1 (dosing of ALPN-101) until the date of best response, assessed up to 36 months)
- Duration of Response (DOR)(From the date of best response until disease progression, assessed up to 36 months)
- Failure-free survival (FFS)(From study Day 1 (dosing of ALPN-101) until relapse, initiation of new systemic therapy, or non-relapse mortality; assessed up to 36 months)
- Event-free survival (EFS)(From study Day 1 (dosing of ALPN-101) until disease (aGVHD)-related event or death due to any cause, assessed up to 36 months)
- Time to maximum observed concentration (tmax) of ALPN-101(From study Day 1 (dosing of ALPN-101) until Day 29)
- Overall survival (OS)(From study Day 1 (dosing of ALPN-101) until death due to any cause, assessed up to 36 months)
- Area under the concentration-time curve (AUC) of ALPN-101(From study Day 1 (dosing of ALPN-101) until Day 29)
- Maximum observed concentration (Cmax) of ALPN-101(From study Day 1 (dosing of ALPN-101) until Day 29)
研究者
研究点 (4)
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