A Phase 1 Study of HB2198 in Participants With Moderately to Severely Active Systemic Lupus Erythematosus (SLE)

Phase 1RecruitingNCT07491900

Hinge Bio30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Systemic Lupus Erthematosus (SLE)Lupus Nephritis (LN)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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) Exclusion Criteria: * Anti CD19 or anti CD20 therapy within 6 months * Active CNS lupus * Significant cardiovascular, pulmonary, hepatic, or uncontrolled systemic disease * Active infection or recent serious infection * Positive HBV DNA or HCV RNA; HIV infection * Major surgery within 4 weeks * Prior organ or stem cell transplant * Current pregnancy or breastfeeding * Recent IVIg or plasmapheresis (\<3 months) * Live vaccine within 30 days * Any condition judged unsuitable by Investigator

Outcomes

Primary Outcomes

Number of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)

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.

Time frame: Day 1, Day 8, Day 14, Day 29

Maximum tolerated dose (MTD)

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.

Time frame: Day 1, Day 8, Day 14, Day 29

Number of participants experiencing dose-limiting toxicities (DLTs)

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.

Time frame: Day 1, Day 8, Day 14, Day 29

Recommended Phase 2 Dose (RP2D)

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.

Time frame: Day 1, Day 8, Day 14, Day 29

Secondary Outcomes

To characterize the pharmacokinetic (PK) profile of HB2198

Concentration of HB2198 and PK parameters such as, area under the concentration versus time curve (AUC)

Time frame: 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

To characterize the pharmacokinetic (PK) profile of HB2198

Concentration of HB2198 and PK parameters such as maximum drug concentration (Cmax)

Time frame: 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

To characterize the pharmacokinetic (PK) profile of HB2198

Concentration of HB2198 and PK parameters such as time to maximum plasma concentration (tmax)

Time frame: 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

To evaluate the development of anti-drug antibodies (ADAs)

Proportion of participants developing ADAs

Time frame: 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

To evaluate B-cell depletion and other pharmacodynamic changes

B cell depletion dynamics (depth, duration, subsets)

Time frame: Screening, Day 1, Day 8, Day 14, Day 29, Month 2, Month 3, Month 6, Month 9, Month 12/End of Study