A Phase 1, Double-blind, Single- and Multiple-ascending Dose Escalation Study of TNB-738, a Biparatopic Antibody Targeting CD38 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Safety and tolerability of TNB-738 by the incidence of treatment emergent adverse events in Multiple Ascending group. Adverse Events will be graded according to the NCI-CTCAE, version 5.0
研究概览
简要总结
This is a Phase 1, Double blind, Single ascending and Multiple ascending dose (SAD and MAD) escalation study in Healthy Volunteers.
详细描述
TNB-738 is a fully human bispecific antibody used to inhibit human CD38 enzyme.
The study will consist of 2 arms (A and B). The SAD arm (Arm A) of the study consists of sequential single dose escalation cohorts, whereas the MAD portion (Arm B) of the study consists of sequential dose escalation cohorts receiving study drug once every 4 weeks for 3 doses. In both Arm A and Arm B, subjects will be randomized to receive either TNB-738 or matching placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female
- •Age 18 - 75
- •Body mass index (BMI) ranging between 18 and 35 kg/m2, inclusive
- •Female subjects of child-bearing potential must agree to use one of the study-approved effective contraceptive methods for the duration of the study
- •Male subjects must practice true abstinence or agree to use a condom while participating in the study through End of study (EOS)
- •If female, a negative serum pregnancy test at Screening and urinary pregnancy test at Day -1 is required
- •Able to read, understand, and provide signed informed consent
- •Able to communicate adequately with the investigator and to comply with the requirements for the entire study.
排除标准
- •Subject has any significant medical condition that would prevent the subject from participating in the study.
- •Subject is pregnant or breastfeeding.
- •Subject is currently receiving treatment with a biologic agent.
- •Subject has a history of anaphylactic reactions to biologic agents.
- •Subject has been dosed with another investigational drug study within 60 days prior to study drug administration.
- •Subject has current or recent (within 4 weeks prior to screening) signs or symptoms of infection that require antibiotic administration.
- •Subject has evidence of COVID-19 infection and/or subject is deemed at risk for the coronavirus disease in the opinion of the investigator or the subject has participated in another clinical study involving treatment(s), which may increase such risk.
- •Subject has used any prescription (excluding hormonal birth control) drugs within 14 days or illicit drugs within 30 days, or 5 half-lives (whichever is longer), prior to study drug administration.
- •Subject has a positive urine drug test or alcohol breath test at screening.
- •Subject has donated or lost more than 1 unit of blood (500 mL) within 60 days or more than 1 unit of serum within 7 days before the study drug administration.
- •Subject is HIV, HBV, or HCV positive.
- •Subject has received a live virus vaccine within 4 weeks of dosing
研究组 & 干预措施
Single Ascending Dose (SAD -Arm A)
Up to 5 cohorts of subjects receiving sequentially ascending dose of TNB-738 or placebo are planned until maximum tolerated dose is reached or recommended phase 2 dose is identified
干预措施: TNB-738 (Drug)
Multiple Ascending Dose (MAD- Arm B)
An expansion cohort (upto 4 cohorts) will be enrolled after maximum tolerated dose or recommended phase 2 dose is established.
干预措施: TNB-738 (Drug)
结局指标
主要结局
Safety and tolerability of TNB-738 by the incidence of treatment emergent adverse events in Multiple Ascending group. Adverse Events will be graded according to the NCI-CTCAE, version 5.0
时间窗: 21 weeks
To investigate the Cmax (maximum Serum concentration) of TNB-738 following Single Ascending Dose.
时间窗: 13 weeks
To investigate the Cmax (Maximum Serum concentration) of TNB-738 following Multiple Ascending Dose
时间窗: 21 weeks
Tmax (time for maximum serum concentration) for Single Ascending Dose
时间窗: 13 weeks
Safety and tolerability of TNB-738 by the incidence of treatment emergent adverse events in Single Ascending group. Adverse Events will be graded according to the NCI-CTCAE, version 5.0
时间窗: 13 weeks
Tmax (time for maximum serum concentration) for Multiple Ascending Dose
时间窗: 21 weeks
Terminal elimination half-life (t1/2) for Single Ascending Dose
时间窗: 13 weeks
Terminal elimination half-life (t1/2) for Multiple Ascending Dose
时间窗: 21 weeks
次要结局
- To determine CD38 enzyme activity following Single Ascending Dose(13 weeks)
- Anti drug antibodies (ADA) as a measurement of immunogenicity following Multiple Ascending Dose of TNB-738(21 weeks)
- Anti drug antibodies (ADA) as a measurement of immunogenicity following Single Ascending Dose of TNB-738(13 weeks)
- To determine CD38 enzyme activity following Multiple Ascending Dose(21 weeks)