Extra-renal Lupus (ERL), Lupus Nephritis (LN), Systemic Lupus Erthematosus (SLE)
Conditions
Brief summary
This Phase 1, open label, dose escalation study evaluates the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of HB2198, a tetravalent bispecific anti CD19/CD20 antibody, in adults with moderately to severely active systemic lupus erythematosus (SLE), including lupus nephritis and extra renal lupus. Approximately 30 participants will receive two intravenous doses of HB2198 and be followed for 12 months to assess safety, B cell depletion, disease activity, immunologic biomarkers, and renal outcomes.
Detailed description
HB2198 is a novel tetravalent bispecific antibody engineered for enhanced B-cell depletion through dual CD19/CD20 targeting and optimized Fc mediated effector function. The study uses a modified 3+3 dose escalation design, enrolling sequential cohorts to receive HB2198 IV on Day 1 and Day 8. Safety, dose limiting toxicities, pharmacokinetics, pharmacodynamics, and immunogenicity will be assessed. Participants will undergo comprehensive disease activity assessments using SLEDAI 2K, PGA, LupusQoL, FACIT Fatigue, and renal response metrics. Total participation is about 13 months.
Interventions
DRUGHB2198
HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains
Sponsors
Hinge Bio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* • Meet 2019 ACR / 2023 EULAR SLE classification criteria * Moderate or high disease activity (SLEDAI 2K ≥6; PGA ≥1) * LN participants: biopsy confirmed active Class III/IV ± V or Class V LN; proteinuria ≥0.8 g/g; eGFR ≥30 mL/min/1.73 m² * ERL participants: inadequate response/intolerance to ≥1 standard SLE therapy * Positive ANA (≥1:80) or SLE associated autoantibodies * Required minimum lab values (lymphocytes ≥500/µL, B cells ≥25/µL, ANC ≥1000/mm³, IgG ≥600 mg/dL, etc.) * Women of childbearing potential: negative pregnancy test; contraception required * Voluntary informed consent
Exclusion criteria
* (Key) Inclusion Criteria: * Meet 2019 ACR / 2023 EULAR SLE classification criteria * Moderate or high disease activity (SLEDAI 2K ≥6; PGA ≥1) * LN participants: biopsy confirmed active Class III/IV ± V or Class V LN; proteinuria ≥0.8 g/g; eGFR ≥30 mL/min/1.73 m² * ERL participants: inadequate response/intolerance to ≥1 standard SLE therapy * Positive ANA (≥1:80) or SLE associated autoantibodies * Required minimum lab values (lymphocytes ≥500/µL, B cells ≥25/µL, ANC ≥1000/mm³, IgG ≥600 mg/dL, etc.) * Women of childbearing potential: negative pregnancy test; contraception required * Voluntary informed consent (Key)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | Day 1, Day 8, Day 14, Day 29 | Safety and tolerability will be assessed primarily by the incidence of TEAEs and SAEs. Supporting safety data (e.g., clinical laboratory values, vital signs, ECG results, physical examinations, and renal function assessments) will be reviewed descriptively to aid interpretation of tolerability but will not be reported as separate outcome measures. |
| Maximum tolerated dose (MTD) | Day 1, Day 8, Day 14, Day 29 | MTD will be determined based on the incidence of dose-limiting toxicities (DLTs) according to protocol-defined criteria. Laboratory results, vital signs, ECGs, physical examinations, and renal assessments will be used to evaluate DLTs but will not be individually reported as outcome measures. |
| Number of participants experiencing dose-limiting toxicities (DLTs) | Day 1, Day 8, Day 14, Day 29 | DLTs will be evaluated based on protocol-defined criteria. Supporting safety data (e.g., labs, vitals, ECGs, physical exams, renal assessments) will be used to determine DLT classification but will not be reported as separate outcome measures. |
| Recommended Phase 2 Dose (RP2D) | Day 1, Day 8, Day 14, Day 29 | The RP2D will be selected using an integrated assessment of DLTs, TEAEs, and overall tolerability, based on protocol-defined safety criteria. Clinical laboratory results, vital signs, ECGs, physical examinations, and renal assessments will be used to inform dose selection but will not be individually reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To characterize the pharmacokinetic (PK) profile of HB2198 | Multiple timepoints collected before and after infusion on dosing days (Day 1, Day 8), and during the follow-up period on Day 14, Day 29, Month 3, Month 12 | Concentration of HB2198 and PK parameters such as, area under the concentration versus time curve (AUC) |
| To evaluate the development of anti-drug antibodies (ADAs) | Multiple timepoints collected before and after infusion on dosing days (Day 1, Day 8), and during the follow-up period on Day 14, Day 29, Month 3, Month 12 | Proportion of participants developing ADAs |
| To evaluate B-cell depletion and other pharmacodynamic changes | Screening, Day 1, Day 8, Day 14, Day 29, Month 2, Month 3, Month 6, Month 9, Month 12/End of Study | B cell depletion dynamics (depth, duration, subsets) |
| To evaluate change from baseline in systemic lupus disease activity | Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study | • Change from baseline in SLEDAI 2K |
Countries
Australia
Contacts
CONTACTJoshua Pelham
CONTACTKristen Quigley
Outcome results
None listed