A Phase 1/2 Study of REGN7257 (Anti-Interleukin 2 Receptor Subunit Gamma [IL2RG] Monoclonal Antibody) in Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 15
- 主要终点
- Incidence of serious adverse events (SAEs)
研究概览
简要总结
This study is researching an experimental drug called REGN7257 (called "study drug"). The study is focused on patients who have severe aplastic anemia (SAA), a disease of the bone marrow resulting in an impairment of the production of blood cells.
The main purpose of this two-part study (Part A and Part B) is to test how safe and tolerable REGN7257 is in patients with SAA in which other Immunosuppressive therapies (ISTs) have not worked well.
The study is looking at several other research questions to better understand the following properties of REGN7257:
- Side effects that may be experienced by participants taking REGN7257
- How REGN7257 works in the body
- How much REGN7257 is present in blood after dosing
- If REGN7257 works to raise levels of certain blood counts after treatment
- How quickly REGN7257 works to raise levels of certain blood counts
- In patients for whom REGN7257 works to raise levels of certain blood counts after treatment, how many continue to show such a response throughout the study
- If REGN7257 works to lower the number of platelet and red blood cell transfusions needed
- How REGN7257 changes immune cell counts and composition
- How the body reacts to REGN7257 and if it produces proteins that bind to REGN7257 (this would be called the formation of anti-drug antibodies [ADA])
详细描述
The trial was intended to be a Phase 1/2 trial, but no participants were enrolled in Phase 2
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Part A: SAA that is IST-refractory or IST-relapsed, as defined in the protocol
- •Part B: SAA that is IST-relapsed, as defined in the protocol
- •Hematopoietic stem cell transplantation (HSCT) is not available or suitable as a treatment option or has been refused by the patient
- •Adequate hepatic and renal function as defined in the protocol
排除标准
- •Diagnosis of Fanconi anemia or other congenital bone marrow failure syndrome as defined in the protocol
- •Evidence of myelodysplastic syndrome as defined in the protocol
- •Paroxysmal nocturnal hemoglobinuria (PNH) with evidence of clinically significant hemolysis (eg, treatment indicated) or history of PNH-associated thrombosis
- •Treatment with a T cell-depleting agent (eg, ATG or alemtuzumab) within 6 months prior to dosing
- •Treatment with a calcineurin inhibitor (eg, cyclosporine) within 4 weeks prior to dosing for patients enrolled in Part A
- •Treatment with eltrombopag or investigational thrombopoietin receptor agonist, Granulocyte Colony-Stimulating Factor (G-CSF), or an androgen (eg, danazol), within 2 weeks prior to dosing
- •HIV, hepatitis B or hepatitis C positive by serological testing at the screening visit as defined in the protocol
- •Active tuberculosis, latent tuberculosis infection (LTBI) or history incompletely-treated tuberculosis or LTBI
- •Active infection as defined in the protocol
- •Note: Other protocol-defined inclusion/ exclusion criteria apply
研究组 & 干预措施
Part A
Part A: Single ascending dose (SAD) escalation cohorts
干预措施: REGN7257 (Drug)
Part B
Part B: Multiple REGN7257 dosages.
干预措施: REGN7257 (Drug)
结局指标
主要结局
Incidence of serious adverse events (SAEs)
时间窗: Through the end of study visit, approximately 78 weeks
Part B
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: Through the end of study visit, approximately 78 weeks
Part B
Overall response rate (ORR)
时间窗: At 6 months, approximately 26 weeks
Part B
Incidence of adverse events (AEs)
时间窗: 12 months post-treatment, approximately 52 weeks
Part A
Incidence of serious adverse events (SAEs)
时间窗: 12 months post-treatment, approximately 52 weeks
Part A
Incidence and severity of treatment-emergent adverse events (TEAEs)
时间窗: 12 months post-treatment, approximately 52 weeks
Part A
次要结局
- Time to best response(Up to 18 months)
- Any clinical response(Until the end of study, approximately week 78)
- Changes in platelet cell counts(Up to 18 months)
- Incidence of treatment-emergent anti-drug antibody (ADA) over time(Up to 12 months)
- ORR(At 3 months, approximately 12 weeks)
- Platelet transfusions per month over time(Up to 18 months)
- Changes in the whole blood immune cell subsets (T cells)(Up to 18 months)
- Changes in the whole blood immune cell subsets (B cells)(Up to 18 months)
- Changes in the whole blood immune cell subsets (NK cells)(Up to 18 months)
- Partial response (PR)(At 3 months, approximately 12 weeks)
- Time to first response(Up to 18 months)
- Red blood cell transfusions per month over time(Up to 18 months)
- Changes in reticulocyte cell counts(Up to 18 months)
- Changes in the whole blood immune cell subsets [Natural killer (NK) cells](Up to 12 months)
- Complete response (CR)(At 3 months, approximately 12 weeks)
- Changes in neutrophil cell counts(Up to 18 months)
- Changes in hemoglobin cell counts(Up to 18 months)
- Changes in lymphocyte cell counts(Up to 18 months)
- Drug concentrations in serum over time(Up to 18 months)
- Incidence of treatment-emergent ADA over time(Up to 18 months)
- Time to first response(Up to 12 months)
- Time to best response(Up to 12 months)
- Changes in lymphocyte cell counts(Up to 12 months)
- Any clinical response(Until the end of study, approximately week 52)
- Platelet transfusions per month over time(Up to 12 months)
- Red blood cell transfusions per month over time(Up to 12 months)
- Changes in neutrophil cell counts(Up to 12 months)
- Changes in hemoglobin cell counts(Up to 12 months)
- Changes in reticulocyte cell counts(Up to 12 months)
- Changes in platelet cell counts(Up to 12 months)
- Changes in the whole blood immune cell subsets (T cells)(Up to 12 months)
- Changes in the whole blood immune cell subsets (B cells)(Up to 12 months)
- Drug concentrations in serum over time(Up to 12 months)