Healthy Volunteer
Conditions
Brief summary
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.
Detailed 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.
Interventions
DRUGHB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains
Drug: HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains administered via IV infusion on Day 1.
DRUGPlacebo comparator: HB2198 Diluent
HB2198 Diluent: single IV infusion
Sponsors
Hinge Bio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
HB2198 and HB2198 Diluent (Placebo)
Eligibility
Sex/Gender
ALL
Age
No minimum to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 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) | Day 1 through Day 28 | DLT's as defined within the protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the pharmacokinetic (PK) profile of HB2198 | Day 1 to Month 2 | Area under the concentration versus time curve (AUC) |
| To characterize the pharmacokinetic (PK) profile of HB2198: | Day 1 to Month 2 | Area Under the Curve to last measurable concentration (AUClast) |
| To evaluate the development of anti-drug antibodies (ADAs) | Day 1 to Month 2 | ADA incidence |
| To evaluate B-cell depletion and other pharmacodynamic changes | Day 1 to Month 2 | B-cell depletion and subsets; duration; change in total immunoglobulins; cytokines/CRP and other biomarkers. |
Countries
Australia
Contacts
CONTACTJoshua Pelham
CONTACTKristen Quigley
Outcome results
None listed