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

Hinge Bio

Status and phase: Enrolling; Phase 1

Conditions: Extra-renal Lupus (ERL); Systemic Lupus Erthematosus (SLE); Lupus Nephritis (LN)

Treatments: Drug: HB2198

Study type: Interventional

Funder types: Industry

Identifiers

NCT07491900

HB2198-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

HB2198

Experimental group

Description:

Drug: HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains administered via IV infusion on Day 1 and Day 8. There are 8 Planned dose levels: 0.1 mg/kg → 16 mg/kg

Treatment:

Drug: HB2198