A Phase 1, Randomized, Double Blinded, Placebo Controlled Dose Escalating Single Ascending Dose Study of HB2198, a Tetravalent Bispecific Anti CD19/CD20 Antibody With Dual Fc Domains, in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
Phase 1, single center, randomized, double blind, placebo controlled SAD study assessing safety, tolerability, PK, PD, and immunogenicity of HB2198 after a single IV infusion in healthy adults. Four dose levels will be explored with sentinel participants per cohort. Approximately 32 participants (6 HB2198:2 placebo per cohort) will be followed for ~2 months, with extended follow up if B-cell counts remain suppressed.
详细描述
HB2198 is a tetravalent bispecific antiCD19/CD20 antibody engineered with dual Fc domains (S239D/I332E) to enhance FcγR engagement. Cohorts (n=8 each) receive a single IV dose of HB2198 or placebo under double blind conditions; 2 sentinels (1 active, 1 placebo) are dosed ≥48 h before the remaining 6 participants. Safety/PK/PD and immunogenicity are characterized through Day 28 and to Month 2, including B-cell depletion kinetics, lymphocyte phenotyping, cytokines, quantitative immunoglobulins, and ADAs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- — 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18-55 years; Healthy Adults
- •IgG ≥ 600 mg/dL
- •Peripheral B cell count within lab normal range
- •Negative pregnancy test (WOCBP) and protocol specified contraception
- •Confinement from Day -1 through ≥24 h after Day 1 dosing
- •Informed consent
排除标准
- •Clinically significant disease that could affect safety or data
- •Hypogammaglobulinemia; active/recent significant infection
- •Chronic antivirals/antimicrobials
- •Recent major surgery; live vaccine <30 days (inactivated ≥14 days before Day 1 recommended)
- •Positive TB screen without treatment
- •HBV DNA+ or HCV RNA+; HIV+
- •Pregnancy/breastfeeding
- •Planned conception or gamete donation within 6 months post dose
研究组 & 干预措施
HB2198 Diluent (IV)
HB2198 Diluent administered via IV infusion on Day 1
干预措施: HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains (Drug)
HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains
HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains administered via IV infusion on Day 1. There are 4 planned dose levels: 0.001 mg/kg → 0.1 mg/kg.
干预措施: Placebo comparator: HB2198 Diluent (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: Time Frame: Day 1 to Day 28; may extend to Month 2
Incidence/severity of AEs and SAEs (CTCAE v5.0)
Dose Limiting Toxicities (DLTs)
时间窗: Day 1 through Day 28
DLT's as defined within the protocol.
次要结局
- To characterize the pharmacokinetic (PK) profile of HB2198(Day 1 to Month 2)
- To characterize the pharmacokinetic (PK) profile of HB2198:(Day 1 to Month 2)
- To evaluate the development of anti-drug antibodies (ADAs)(Day 1 to Month 2)
- To evaluate B-cell depletion and other pharmacodynamic changes(Day 1 to Month 2)