A Phase 1/2, Open-Label Study to Evaluate the Safety and Efficacy of Dibotatug in Adults With Bone Marrow Failure Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 试验地点
- 10
- 主要终点
- Efficacy of dibotatug in participants with BMF syndromes
研究概览
简要总结
This is a multicenter, open-label, Phase 1/2 basket study to evaluate the safety and efficacy of Dibotatug (DR-01) in adults with Bone Marrow Failure syndromes.
详细描述
Study DR-01-HEM-001 is an open-label Phase 1/2 study evaluating the safety and efficacy of dibotatug in adult patients with BMF syndromes. Participants will be enrolled across three cohorts. Cohort A includes relapsed Severe Aplastic Anemia participants, Cohort B includes refractory Severe Aplastic Anemia participants, and Cohort C includes relapsed or refractory transfusion dependent Nonsevere Aplastic Anemia participants. Stage 1 will evaluate the safety and preliminary efficacy in up to 12 evaluable participants, and if deemed appropriate by a Safety Review Committee, the study will continue to enroll in Stage 2 for a total of up to 60 participants.
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 old
- •Women of childbearing potential and males must agree to use 2 methods of effective contraception, with at least 1 method being highly effective.
- •Inclusion Criteria for Severe Aplastic Anemia (SAA) (Cohorts A and B):
- •Participants with SAA must have a current or prior diagnosis of SAA or very SAA.
- •Inclusion Criteria for Refractory Severe Aplastic Anemia (Cohort A) Participants with refractory SAA must have:
- •Received one ≥ 3-month course of ATG and/or CSA-based IST.
- •Refractory SAA, defined as failure to achieve CR or PR ≥ 3 months after starting ATG and/or CSA-based IST.
- •Inclusion Criteria for Relapsed Severe Aplastic Anemia (Cohort B):
- •Relapsed SAA, defined as relapse following a CR or PR that was achieved ≥ 3 months after starting ATG- and/or cyclosporine A (CSA)-based IST.
- •Inclusion Criteria for Relapsed or Refractory Transfusion-Dependent Non-Severe Aplastic Anemia (Cohort C):
- •Current or prior diagnosis of NSAA
- •No current or prior diagnosis of SAA.
- •Received at least 1 prior course of IST such as ATG- or CSA, with or without a TPO-R agonist (lasting ≥ 3 months).
- •Meets criteria for transfusion dependence (either RBC or platelet):
- •RBC transfusion dependence: transfusion of ≥ 2 units of RBCs in the past 56 days
- •Platelet transfusion dependence: transfusion of ≥ 1 unit of apheresis platelets in the past 28 days
- •Participants entering the Extension Treatment Period must meet the following criteria:
- •Signed informed consent form (ICF) for the Extension Treatment Period.
- •CR or PR by Week 24 during the Main Treatment Period
排除标准
- •Diagnosis of Fanconi anemia, dyskeratosis congenita, or other congenital BMF syndrome.
- •Prior HCT.
- •Planning to receive HCT as treatment for AA.
- •Evidence of a clonal disorder with poor risk cytogenetics per Revised International Prognostic Scoring System (IPSS-R) for MDS.
- •Diagnosis of PNH or a clonal hematologic bone marrow disorder such as LGLL. Existence of PNH clones, LGLL cells, or clonal hematopoiesis of indeterminate potential (CHIP) clones without a clinical diagnosis is not exclusionary.
- •Use of a T-cell depleting agent (e.g., ATG, alemtuzumab, thymoglobulin) within 3 months prior to Day
- •Use of a B-cell depleting agent (e.g., rituximab, ocrelizumab, ofatumumab, ublituximab) within 28 days prior to Day
- •Use of any of the following within 14 days of Day 1, unless used as an established therapy at screening and there is evidence of either progressive cytopenia or lack of count improvement over the 3 months before screening:
- •Calcineurin inhibitor (e.g., cyclosporine), TPO-R agonist (e.g., eltrombopag), Androgen (e.g., danazol), Oral Janus kinase (JAK) inhibitor
- •Regardless of their use as an established therapy at screening, use of the above medications is prohibited for all participants from 3 months after Day
- •Current infection not adequately responding to appropriate therapy or requiring hospitalization.
- •Current uncontrolled or invasive infection with cytomegalovirus (CMV), Epstein Barr virus (EBV), varicella zoster virus (VZV), herpes simplex virus (HSV), or human T-lymphotropic virus-1 (HTLV-1), defined by polymerase chain reaction (PCR) at screening. Note that low level CMV, EBV, or VZV viremia is not exclusionary.
- •Human immunodeficiency virus (HIV) infection.
- •Current or prior infection with hepatitis B virus (HBV)
- •Current hepatitis C virus (HCV) infection
- •Latent tuberculosis (TB) infection as indicated by IFN-γ release assay without documentation of appropriate treatment (appropriate therapy as defined by the World Health Organization [WHO] and/or the United States Centers for Disease Control and Prevention).
- •Estimated glomerular filtration rate < 30 mL/min/1.73 m2 at screening (using the Chronic Kidney Disease Epidemiology Collaboration formula; Levey 2009).
- •Total bilirubin > 1.5 × upper limit of normal (ULN) (> 3 × ULN if known Gilbert's disease).
- •Aspartate aminotransferase or alanine aminotransferase > 2.5 × ULN (except in participants with known iron overload).
研究组 & 干预措施
Dibotatug (DR-01)
Subjects in this arm will receive 20 weeks of dosing with dibotatug. Subjects with a CR or PR by Week 24 have the option to continue dosing through Week 48; Dibotatug will be administered via IV infusion.
干预措施: Dibotatug (DR-01) (Drug)
结局指标
主要结局
Efficacy of dibotatug in participants with BMF syndromes
时间窗: By 6 months
Overall response rate (complete response \[CR\] + partial response \[PR\]), as defined in disease-specific hematologic criteria
Safety and tolerability of dibotatug in participants with BMF syndromes
时间窗: 52 weeks
Incidence, severity, and relationship of treatment-emergent adverse events (TEAEs), changes in clinical laboratory values, and vital signs
Overall Response Rate of Dibotatug (defined as proportion of subjects with a Complete Response or Partial Response) [Efficacy]
时间窗: By 6 months
Overall Response Rate (ORR), defined as the proportion of subjects with Complete Response (CR) or Partial Response (PR) based on disease-specific response criteria.
Incidence and severity of adverse events as assessed by CTCAE v6.0 [Safety and Tolerability]
时间窗: 52 weeks
Incidence and severity of adverse events as assessed by CTCAE v6.0.
次要结局
未报告次要终点