BeCoMe-9: A Phase 1/2 Dose Escalation and Expansion Study of BE-101 for the Treatment of Adults With Moderately Severe or Severe Hemophilia B
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- Adverse events (AEs) and Serious Adverse Events (SAEs)
研究概览
简要总结
The BeCoMe-9 Study (BE-101-01) is a Phase 1/2, first in human, multi-center, open-label, dose-escalation study to evaluate the safety and clinical activity of a single intravenous (IV) dose of BE-101 in adults with moderately severe or severe Hemophilia B. Once infused, BE-101 is designed to engraft and continuously secrete FIX into the circulation to restore clinically meaningful levels of active FIX. BE-101 is an autologous (person's own cells) B Cell Medicine (BCM) which uses CRISPR/Cas9 gene editing to precisely insert human FIX gene into those cells.
详细描述
The study includes 2 distinct parts: Part 1 and Part 2. In Part 1, an ascending-dose design will be utilized to enable evaluation of increasing doses in a stepwise manner. The objective for this dose escalation is to identify the dose of BE-101 required to achieve desired FIX activity 28 days after infusion. Upon identification of a safe and efficacious dose in Part 1, an expansion phase (Part 2) will initiate. The initial cohort in the Part 2 expansion (Part 2a) phase will include up to 6 adult participants to further characterize the safety and activity of BE-101 at the selected dose. Additional cohorts for adolescents and redosing for participants in Part 1 of the study will occur following data availability of Part 1.
Up to 24 participants will be enrolled across Part 1 (up to 18) and Part 2a (up to 6). Consented participants will complete a screening period to assess eligibility and upon enrollment will undergo leukapheresis collection to support BE-101 manufacturing. Following administration, participants will be monitored for safety and clinical activity. The total duration of study participation is approximately 52 weeks post IV administration of BE-101.
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Adult Males (≥18) with moderately severe to severe Hemophilia B (FIX deficiency)
- •Received ≥50 exposure days to Factor IX products preceding enrollment.
- •Currently receiving prophylaxis treatment
- •Adequate organ function and clinical labs
- •Able to tolerate study procedures including leukapheresis.
排除标准
- •Pre-existing or history of specific diseases
- •B-Cell malignancy, EBV lymphoproliferative disease
- •Primary immunodeficiency disease or disorder (PIDD) or systemic immuno-suppression
- •Arterial and/or venous thromboembolic events within 2 years prior to dosing
- •History of anaphylaxis or nephrotic syndrome
- •Active infection (HIV, Hep B or C)
- •History of inhibitor to FIX or inhibitor
- •History of an allergic reaction or anaphylaxis to FIX products
- •Planned surgical procedure within 6 months from BE-101 administration
- •Previously dosed with gene therapy
- •Participated in an interventional study and/or received an interventional study drug within 30 days or five-half-lives (whichever is longer) of consent into BeCoMe-9 and for the duration of the study
- •Planned participation in clinical trial within one year after BE-101
- •Administration of an investigational agent or vaccine within 28 days of leukapheresis and dosing of BE-101
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Part 1 - Dose Escalation, Dose Level 1
干预措施: BE-101 (Drug)
Part 1 - Dose Escalation, Dose Level 2
干预措施: BE-101 (Drug)
Part 1 - Dose Escalation, Dose Level 3
干预措施: BE-101 (Drug)
Part 2 - Dose Expansion, Cohort 2a Adult Expansion, Optimal Dose Selected in Part 1 Dose Escalation
干预措施: BE-101 (Drug)
结局指标
主要结局
Adverse events (AEs) and Serious Adverse Events (SAEs)
时间窗: 1 year post dose
Incidence of AEs and SAEs
次要结局
- FIX Activity(Baseline to 1 year post dose)
- FIX Inhibitor(1 year post dose)
- Annualized Bleed Rate (ABR)(1 year post dose)
- Bleeding Episodes(1 year post dose)
- Target Joints(1 year post dose)
- FIX Antigen Concentration(Baseline to 1 year post dose)
- Exogenous FIX Concentrate(1 year post dose)
- FIX Replacement Therapy(1 year post dose)