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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат HB2198
  HB2198, a Tetravalent Bispecific Anti-CD19/CD20 Antibody with Dual Fc Domains

Первичные конечные точки

• Number of participants experiencing treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) [Срок оценки: Day 1, Day 8, Day 14, Day 29]
• Maximum tolerated dose (MTD) [Срок оценки: Day 1, Day 8, Day 14, Day 29]
• Number of participants experiencing dose-limiting toxicities (DLTs) [Срок оценки: Day 1, Day 8, Day 14, Day 29]
• Recommended Phase 2 Dose (RP2D) [Срок оценки: Day 1, Day 8, Day 14, Day 29]

Вторичные конечные точки (11)

• To characterize the pharmacokinetic (PK) profile of HB2198 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Day 29, Month 3, Month 6, Month 9, Month 12]
• To evaluate change from baseline in systemic lupus disease activity [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Screening, Day 1, Day 14, Day 29, Month 2, Month 3, Month 4, Month 6, Month 9, Month 12/End of Study]

Критерии участия

Критерии включения

• • 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

Критерии исключения

• (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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Австралия · 1 центр

• Investigational site — Brisbane

Идентификаторы

NCT: NCT07491900 · HB2198-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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