Overview
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.
Description
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.
Eligibility
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
