A Phase 1b, Double-Blind, Multiple Ascending Dose Study to Assess Safety, Tolerability and Pharmacokinetics of DX-2930 in Hereditary Angioedema Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 38
- 试验地点
- 14
- 主要终点
- Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) profile of multiple subcutaneous administrations of DX-2930 across a range of doses in HAE participants.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •At least 18 years of age at the time of screening
- •Documented diagnosis of HAE (Type I or II)
- •Experiencing ≥2 HAE attacks per year, with at least 1 attack in the past 6 months reported by the participant
- •Willing and able to read, understand, and sign an informed consent form
- •Females of childbearing potential must agree to be abstinent or else use acceptable forms of contraception throughout study
- •Males with female partners of childbearing potential must agree to be abstinent or use a medically acceptable form of contraception throughout study
排除标准
- •Exposure to an investigational drug or device within 90 days prior to study
- •History of exposure within the past 5 years to a monoclonal antibody or recombinant protein bearing an Fc domain
- •Concomitant diagnosis of another form of chronic angioedema
- •Use of long-term prophylaxis for HAE within 90 days prior to study
- •Use of C1-INH that exceeds a total of 30 days within the past 90 days prior to study; any use of C1-INH within 7 days prior to study
- •Exposure to angiotensin-converting enzyme (ACE) inhibitors or any estrogen-containing medications with systemic absorption within 90 days prior to study
- •Exposure to androgens within 90 days prior to study
- •Presence of an indwelling catheter
- •Diagnosis of HIV
- •Active liver disease or liver function test abnormalities
- •History of substance abuse or dependence
- •Pregnancy or breastfeeding
- •Any condition that, in the opinion of the Investigator, may compromise their safety or compliance, preclude successful conduct of the study, or interfere with interpretation of the results
研究组 & 干预措施
DX-2930, Cohort 1
Participants will receive 30 milligram (mg) dose of DX-2930 subcutaneous (SC) injection once and followed by the second dose after 2 week into the upper arm.
干预措施: DX-2930 (Drug)
DX-2930, Cohort 2
Participants will receive 100 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
干预措施: DX-2930 (Drug)
DX-2930, Cohort 3
Participants will receive 300 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
干预措施: DX-2930 (Drug)
DX-2930, Cohort 4
Participants will receive 400 mg dose of DX-2930 subcutaneous (SC) injection once and followed by the second dose after 2 week into the upper arm.
干预措施: DX-2930 (Drug)
Placebo
Participants will receive placebo matched to 30, 100, 300 and 400 mg dose of DX-2930 SC injection once and followed by the second dose after 2 week into the upper arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Serious Adverse Events (SAE) and Treatment-Emergent Adverse Events (TEAE)
时间窗: From Day 1 up to final follow-up (Day 123)
A SAE was any adverse experience occurring at any dose that resulted in any of the following outcomes: Death, Life-threatening experience, required inpatient hospitalization or prolongation of existing hospitalization. Resulted in persistent or significant disability or incapacity. Was a congenital anomaly or birth defect. Was considered to be an important medical event. An AE was considered treatment-emergent if the onset time was after administration of study drug through the Day 120 post-dose final follow-up visit or, in the event that onset time preceded study drug administration, the AE increased in severity during the 120-day post-dose follow-up period.
次要结局
- Apparent Clearance (CL/F)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)
- Terminal Elimination Half-Life (t1/2)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)
- Time to Maximum Plasma Concentration (Tmax)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)
- Area Under the Plasma Concentration-Time Curve (AUC)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)
- Apparent Volume of Distribution (Vd/F)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)
- Maximum Plasma Concentration (Cmax)(Days 1, 2, 4, 8, 15, 16, 18, 22, 29, 36, 50, 64, 92, and 120)