A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of JSP191 for Hematopoietic Cell Transplantation Conditioning to Achieve Engraftment and Immune Reconstitution in Subjects With SCID
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 23
- 试验地点
- 9
- 主要终点
- Phase 1: Safety and tolerability of JSP191 as conditioning therapy in SCID patients undergoing HCT: adverse events
研究概览
简要总结
A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with Severe Combined Immune Deficiency undergoing blood stem cell transplantation
详细描述
A Phase 1/2 study to evaluate the safety, tolerability, and efficacy of an antibody conditioning regimen, known as JSP191, in patients with SCID undergoing blood stem cell transplantation. Blood Stem Cell transplantation offers the only potentially curative therapy for SCID.
The biological conditioning regimen, JSP191, is an antibody that binds to CD117. CD117 is the receptor for Stem Cell Factor on blood forming cells. CD117 binding to Stem Cell Factor is critical for survival and maintenance of blood forming stem cells. The binding of JSP191 to CD117 blocks CD117 from binding to Stem Cell Factor on blood forming stem cells. In the absence of CD117/Stem Cell Factor binding, hematopoietic stem cells that are currently occupying the bone marrow niches in SCID patients exit from the bone marrow.
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
- 3 Months 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Typical SCID as defined by Primary Immune Deficiency Treatment Consortia including but not limited to the following subtypes:
- •T-, B+, NK-: IL-2Rcγ deficient, JAK3-deficient (no longer enrolling)
- •T-, B-, NK+: RAG1/2 deficient, Artemis-deficient
- •T-, B+, NK+: IL7Rα deficient, CD3 subunit deficient, CD45 deficient (no longer enrolling) OR Variant SCID with absent or low T cell function, Omenn syndrome, Leaky SCID, Reticular dysgenesis, Adenosine deaminase deficiency, and Purine nucleoside phosphorylase deficiency may be included after consultation with the medical monitor.
- •Patients with human leukocyte antigen (HLA) matched related or unrelated donors
- •Adequate end organ function as defined in study protocol
- •Age ≤ 12 years
- •Prior donor of appropriate age (≥ 5 years old) available for re-collection of stem cells
- •Previous allogeneic Hematopoietic Cell Transplantation HCT (≥ 6 months post initial transplant) with poor graft function
排除标准
- •Patients with any acute or uncontrolled infections
- •Patients receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
- •Patients with active malignancies
- •Active GVHD within 6 months prior to enrollment, or on immunosuppressive therapy for GVHD
研究组 & 干预措施
Blood Stem Cell Transplant w/ anti-CD117 conditioning
The study will enroll two groups: Group A: previously transplanted SCID patients; Group B: newly diagnosed SCID. The study plans to assess JSP191 in different dose cohorts. Patients will receive a single dose of intravenous JSP191 antibody followed by monitoring for antibody clearance. Once the antibody has cleared below a certain level, patients will receive stem cell transplant and be monitored for hematopoietic recovery.
干预措施: Humanized anti-CD117 Monoclonal Antibody (JSP191) (Biological)
结局指标
主要结局
Phase 1: Safety and tolerability of JSP191 as conditioning therapy in SCID patients undergoing HCT: adverse events
时间窗: Up to 5 years post Donor Cell Transplant (28 days dose limiting toxicity period)
The number of subjects experiencing dose limiting toxicities including adverse events and serious adverse events will be assessed.
Phase 2: Efficacy of JSP191 as conditioning therapy in SCID patients
时间窗: Weeks 36-104 post Donor Cell Transplant
To enable immune reconstitution, as determined by the production of naive T cells
次要结局
未报告次要终点