A Phase 1b Open-Label, Single Ascending Dose Study to Evaluate the 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
- 23
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The main objective is to assess the safety and tolerability of budoprutug in adults with SLE. Pharmacokinetics, pharmacodynamics, and preliminary clinical efficacy will also be assessed.
详细描述
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, open-label study will evaluate budoprutug administered as a single intravenous infusion 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 following a single infusion.
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 >=
- •Inadequate response to at least 2 therapeutic interventions, including at least one oral immunosuppressive or biologic standard-of care therapy.
排除标准
- •Active neuropsychiatric SLE.
- •History of inflammatory or autoimmune diseases including, but not limited to, rheumatoid arthritis, scleroderma, myositis, vasculitis, inflammatory bowel disease, or other conditions that require immune suppressive therapy. Subjects with stable concurrent Sjogren's, asthma, or autoimmune thyroid disease may be considered for participation.
- •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
干预措施: Budoprutug (Drug)
Cohort 2: Dose Level B
干预措施: Budoprutug (Drug)
Cohort 3: Dose Level C
干预措施: Budoprutug (Drug)
Cohort 4: Dose Level D
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 24
Number of participants experiencing TEAEs, graded per NCI CTCAE v5.0.
Incidence of Clinical Laboratory Abnormalities
时间窗: Up to Week 24
Number of participants with clinically significant laboratory abnormalities.
Change from Baseline in Systolic Blood Pressure
时间窗: Up to Week 24
Mean change from baseline in systolic blood pressure (mmHg).
Change from Baseline in Diastolic Blood Pressure
时间窗: Up to Week 24
Mean change from baseline in diastolic blood pressure (mmHg).
Change from Baseline in Heart Rate
时间窗: Up to Week 24
Mean change from baseline in heart rate (bpm).
Change from Baseline in Respiratory Rate
时间窗: Up to Week 24
Mean change from baseline in respiratory rate.
Change from Baseline in Body Temperature
时间窗: Up to Week 24
Mean change from baseline in body temperature (°C).
Change from Baseline in PR Interval
时间窗: Up to Week 24
Mean change from baseline in PR interval (ms).
Change from Baseline in QRS Duration
时间窗: Up to Week 24
Mean change from baseline in QRS duration (ms).
Change from Baseline in QT Interval
时间窗: Up to Week 24
Mean change from baseline in QT interval (ms).
Change from Baseline in QTc Interval
时间窗: Up to Week 24
Mean change from baseline in corrected QT interval (QTc).
次要结局
- Area Under the Curve (AUC) of Budoprutug(Up to Week 24)
- Maximum Observed Plasma Concentration (Cmax)(Up to Week 24)
- Time to Maximum Observed Concentration (Tmax)(Up to Week 24)
- Terminal Half-Life (T1/2)(Up to Week 24)
- Apparent Clearance (CL/F) of budoprutug(Up to Week 24)
- Volume of Distribution (Vd)(Up to Week 24)
- Change from Baseline in Circulating B Cell Count(Up to Week 24)
- Incidence of Anti-Drug Antibodies (ADAs)(Up to Week 24)
- ADA Titer Over Time(Up to Week 24)