A Phase 1b/2a, Open-Label, Sequential-Cohort, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Effectiveness of Budoprutug (TNT119) in Subjects With Immune Thrombocytopenia (ITP)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 24
- 试验地点
- 26
- 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 ITP. 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/2a, open-label, sequential-cohort, dose escalation and expansion study will evaluate the safety, tolerability, PK, PD, and preliminary clinical effectiveness of budoprutug in subjects with ITP. Budoprutug will be administered as two (2) IV infusions 14 days apart in ascending dose cohorts of patients aged 18 years and above with a platelet count < 30,000/µL despite an adequate trial of at least one prior therapeutic attempt.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 years at the time of consent.
- •Platelet count < 30,000/µL despite an adequate trial of at least one prior therapeutic attempt. Platelet counts of < 30,000/µL must be confirmed on 2 occasions at least 5 days apart, but no more than 14 days apart.
- •Partial thromboplastin time < 1.5 x upper limit of normal (ULN), prothrombin time < 1.5 x ULN, total bilirubin < 1.5 x ULN unless due to Gilbert's syndrome, or an international normalized ratio < 1.5 at screening.
排除标准
- •CD19+ B cell count < 80 cells/µL at Screening, or < 40 cells/µL if B-cell depleting therapy was received within 24 weeks to 2 years prior.
- •Diagnosis of paroxysmal nocturnal hemoglobinuria, Evan's Syndrome, or other bleeding disorders affecting safety or data integrity.
- •Prior B-cell depleting therapy (e.g., rituximab) within 24 weeks before first dose or planned during the study.
- •Chronic use of anticoagulants or antiplatelet agents (e.g., aspirin, NSAIDs, thienopyridines) within 14 days before dosing through follow-up. Intermittent NSAID use is allowed.
- •Immunosuppressants (excluding corticosteroids) within 30 days or 5× half-life before Screening; alkylating agents within 180 days.
- •IVIg treatment within 90 days prior to Screening.
- •Active ITP treatment (other than steroids or TPO agonists) within 30 days or 5× half-life before first dose, unless approved by Medical Monitor.
- •Active, chronic, or latent infections including hepatitis B/C or HIV.
- •Active TB or high TB risk.
研究组 & 干预措施
Cohort 2: Dose Level B
Single IV dose of study product on Day 1 and on Day 15
干预措施: Budoprutug (Drug)
Cohort 3: Dose Level C
Single IV dose of study product on Day 1 and on Day 15
干预措施: Budoprutug (Drug)
Dose Expansion Cohort
Single IV dose of study product on Day 1 and Day 15
干预措施: Budoprutug (Drug)
Cohort 1: Dose Level A
Single IV dose of study product on Day 1 and on 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 48
Number of participants experiencing TEAEs, graded per NCI CTCAE v5.0.
次要结局
- Apparent Clearance (CL/F)(Up to week 48)
- Area Under the Curve (AUC)(Up to week 48)
- Maximum Observed Plasma Concentration (Cmax)(Up to week 48)
- Time to Maximum Observed Concentration (Tmax)(Up to week 48)
- Terminal Half-Life (T1/2)(Up to week 48)
- Change from Baseline in CD20+ B-cell Count(Up to week 48)
- Change in Platelet Count(Up to week 48)
- Proportion of Participants with stable, partial or complete platelet response(Up to week 48)
- Incidence of Anti-Drug Antibodies (ADAs)(Up to week 48)
- Steroid Discontinuation Rate(Up to week 48)