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

A Phase 1, Open Label Dose Escalating Study of HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody With Dual Fc Domains, in Patients With Moderately to Severely Active Systemic Lupus Erythematosus

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.

Study Overview

• Status: Recruiting
• Conditions: Lupus Nephritis (LN); Systemic Lupus Erthematosus (SLE); Extra-renal Lupus (ERL)
• Intervention / Treatment: Drug: HB2198

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Joshua Pelham; Phone Number: 1-415-378-4738; Email: joshua.pelham@hingebio.com
• Study Contact Backup: Name: Kristen Quigley; Email: kristen.quigley@hingebio.com

Study Locations

• Australia
  • Brisbane, Australia
    • Recruiting
    • Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HB2198; 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	Drug: HB2198; HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	Day 1, Day 8, Day 14, Day 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To characterize the pharmacokinetic (PK) profile of HB2198	Concentration of HB2198 and PK parameters such as, area under the concentration versus time curve (AUC)	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)	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)	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	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)	Screening, Day 1, Day 8, Day 14, Day 29, Month 2, Month 3, Month 6, Month 9, Month 12/End of Study
To evaluate change from baseline in systemic lupus disease activity	• Change from baseline in SLEDAI 2K	Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study
To evaluate change from baseline in systemic lupus disease activity	• Achievement of Lupus Low Disease Activity State (LLDAS)	Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study
To evaluate change from baseline in systemic lupus disease activity	• Renal response: CRR/PRR	Day 29, Month 3, Month 6, Month 9, Month 12
To evaluate change from baseline in systemic lupus disease activity	• Change in LupusQoL	Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study
To evaluate change from baseline in systemic lupus disease activity	• Change in FACIT Fatigue scores	Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study
To evaluate change from baseline in systemic lupus disease activity	• Change in Physician Global Assessment (PGA)	Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study

Collaborators and Investigators

• Sponsor: Hinge Bio

Study record dates

Study Major Dates

• Study Start (Estimated): March 23, 2026
• Primary Completion (Estimated): October 24, 2027
• Study Completion (Estimated): October 24, 2028

Study Registration Dates

• First Submitted: February 18, 2026
• First Submitted That Met QC Criteria: March 18, 2026
• First Posted (Actual): March 25, 2026

Study Record Updates

• Last Update Posted (Actual): March 25, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Lupus Erythematosus, Systemic; Nephritis; Skin and Connective Tissue Diseases; Lupus Nephritis
• Other Study ID Numbers: HB2198-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: This is still being actively discussed. A decision will be made during the course of the study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No