A Phase 1b/2a Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Budoprutug (TNT119) in Adult Subjects With Systemic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
Budoprutug is a humanized, immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to CD19 and is projected to deplete targeted cells through antibody-dependent cellular cytotoxicity. This Phase 1b/2a, open-label study will evaluate budoprutug in ascending dose cohorts of patients aged 18 years and above with active, seropositive SLE and inadequate response to standard therapy. The study will also assess the pharmacokinetics, pharmacodynamics and early indications of efficacy of budoprutug in SLE, where pharmacodynamics will be evaluated as the change in the number of B cells and immunoglobulins (antibodies) in the blood over time. Budoprutug will be administered as two (2) IV infusions 14 days apart in ascending dose cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 65 years at the time of consent.
- •Diagnosis of SLE according to the 2019 European League Against. Rheumatism and the American College of Rheumatology (ACR) classification criteria.
- •Active, seropositive disease, with SLEDAI 2K >=6 at screening
- •Inadequate response to at least one therapeutic intervention
排除标准
- •Active neuropsychiatric SLE.
- •Active lupus nephritis type III or IV that is expected to require induction therapy during the study or recently treated with induction therapy within 12 weeks.
- •Prior diagnosis of, or fulfills diagnostic criteria for, other autoimmune or inflammatory disease that may confound clinical assessments or increase subject risk in the study
- •Active systemic infection or history of chronic, recurrent, latent, or recent serious infections.
研究组 & 干预措施
Cohort 1: Dose Level A
Single IV dose at Day 1 and Day 15
干预措施: Budoprutug (Drug)
Cohort 3: Dose Level C
Single IV dose at Day 1 and Day 15
干预措施: Budoprutug (Drug)
Cohort 2: Dose Level B
Single IV dose at Day 1 and Day 15
干预措施: Budoprutug (Drug)
Dose Expansion Cohort
Single IV dose at Day 1 and Day 15
干预措施: Budoprutug (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to week 28
Number of participants experiencing TEAEs, graded per NCI CTCAE v6.0.
Incidence of Clinical Laboratory Abnormalities
时间窗: Up to week 28
Number of participants with clinically significant laboratory abnomalities.
Incidence of dose-limiting toxicities (DLTs)
时间窗: up to 28 weeks
Number of incidences of dose-limiting toxicities (DLTs)
Change from Baseline in Systolic Blood Pressure
时间窗: Up to week 28
Mean change from baseline in diastolic blood pressure (mmHg).
Change from Baseline in Diastolic Blood Pressure
时间窗: up to 28 weeks
Mean change from baseline in systolic blood pressure (mmHg).
Change from Baseline in Heart Rate
时间窗: up to 28 weeks
Mean change from baseline in heart rate (bpm).
Change from Baseline in Respiratory Rate
时间窗: up to 28 weeks
Mean change from baseline in respiratory rate
Change from Baseline in Body Temperature
时间窗: up to 28 weeks
Mean change from baseline in body temperature (°C)
Change from Baseline in PR Interval
时间窗: up to 28 weeks
Mean change from baseline in PR interval (ms)
Change from Baseline in QRS Duration
时间窗: up to 28 weeks
Mean change from baseline in QRS duration (ms)
Change from Baseline in QT Interval
时间窗: up to 28 weeks
Mean change from baseline in QT interval (ms)
Change from Baseline in QTc Interval
时间窗: up to 28 weeks
Mean change from baseline in corrected QT interval (QTc)
次要结局
- Area Under the Curve (AUC)(Up to week 28)
- Terminal Half-Life (T1/2)(Up to week 28)
- Incidence of Anti-Drug Antibodies (ADAs)(Up to week 28)
- ADA Titer Over Time(Up to week 28)
- Change from Baseline in CD20+ B-cell Count(Up to week 28)
- Change from Baseline in SLEDAI-2K Score(up to 28 weeks)
- Change from Baseline in Urine Protein Creatinine Ratio (UPCR)(up to 28 weeks)