A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Ascending Doses of REGN7508, a Monoclonal Antibody Against Factor XI, in Healthy Adult Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Incidences of treatment-emergent adverse events (TEAE)
研究概览
简要总结
This study is researching an experimental drug called REGN7508 (called "study drug"). The aim of this study is to see how safe and tolerable the study drug is in healthy participants.
This study is looking at several other research questions, including:
- What side effects may happen from taking the study drug
- How much study drug is in the blood at different times
- Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Body mass index between 18.0 and 32.5 kg/m2 (inclusive) at the screening visit
- •Judged by the investigator to be in good health based on medical history, physical examination, vital sign measurements, and echocardiograms (ECGs) performed at screening and/or prior to administration of initial dose of study drug
- •Participant is in good health based on laboratory safety testing obtained at the screening visit and/or prior to administration of initial dose of study drug
- •Normal activated partial thromboplastin time (aPTT), normal prothrombin time (PT), and normal platelet counts at screening period and at the day -1 visit as defined by the local laboratory
- •Hemoglobin value ≥11.0 g/dL for females and ≥12.9 g/dL for males at the screening and day 1 visits
排除标准
- •History of any major surgical procedure or clinically significant physical trauma, in the opinion of the investigator, that may pose a risk to the participant by study participation
- •Whole blood donation within the previous 56 days or plasma donation within the previous 7 days prior to the screening visit
- •History of clinically significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, psychiatric, neurological, or dermatologic disease, as assessed by the investigator, that may confound the results of the study or poses an additional risk to the participant by study participation, as defined in the protocol
- •Estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m2 at screening
- •Current smoker or former smoker, including e-cigarettes, who stopped smoking within 12 months prior to the screening visit
- •Confirmed positive drug test result at the screening visit and/or prior to randomization or a history of drug abuse within a year prior to the screening visit
- •History of alcohol abuse within the last 2 years prior to the day 1 visit
- •Any malignancy, except for nonmelanoma skin cancer or cervical/anus in situ, that have been resected with no evidence of metastatic disease for 3 years prior to the screening visit
- •History of significant multiple and/or severe allergies (eg, latex gloves) or has had an anaphylactic reaction to prescription or nonprescription drugs or food
- •NOTE: Other Protocol Defined Inclusion / Exclusion Criteria Apply
研究组 & 干预措施
Optional: Cohort 8 Highest IV or SC Dose
Randomized 3:1
干预措施: Matching Placebo (SC) (Drug)
Cohort 1 Lowest IV Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Cohort 1 Lowest IV Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 2 Low IV Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Cohort 2 Low IV Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 3 Mid IV Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Cohort 3 Mid IV Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 4 High IV Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Cohort 4 High IV Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 5 Higher IV Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Cohort 5 Higher IV Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 6 High SC Dose
Randomized 3:1
干预措施: REGN7508 (SC) (Drug)
Cohort 6 High SC Dose
Randomized 3:1
干预措施: Matching Placebo (SC) (Drug)
Cohort 7 Higher SC Dose
Randomized 3:1
干预措施: REGN7508 (SC) (Drug)
Cohort 7 Higher SC Dose
Randomized 3:1
干预措施: Matching Placebo (SC) (Drug)
Optional: Cohort 8 Highest IV or SC Dose
Randomized 3:1
干预措施: REGN7508 (IV) (Drug)
Optional: Cohort 8 Highest IV or SC Dose
Randomized 3:1
干预措施: REGN7508 (SC) (Drug)
Optional: Cohort 8 Highest IV or SC Dose
Randomized 3:1
干预措施: Matching Placebo (IV) (Drug)
Cohort 9 High SC Dose
Randomized 3:1
干预措施: REGN7508 (SC) (Drug)
Cohort 9 High SC Dose
Randomized 3:1
干预措施: Matching Placebo (SC) (Drug)
Optional: Cohort 10 Highest SC Dose
Randomized 3:1
干预措施: REGN7508 (SC) (Drug)
Optional: Cohort 10 Highest SC Dose
Randomized 3:1
干预措施: Matching Placebo (SC) (Drug)
结局指标
主要结局
Incidences of treatment-emergent adverse events (TEAE)
时间窗: Up to 36 days
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period.
Severity of TEAE
时间窗: Up to 36 days
Treatment-emergent adverse events are defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period.
次要结局
- Change from baseline in activated partial thromboplastin time (aPTT)(Up to 36 days)
- Change from baseline in prothrombin time (PT)(Up to 36 days)
- Concentrations of total REGN7508 in serum(Up to 36 days)
- Concentrations of functional REGN7508 in plasma(Up to 36 days)
- Absolute concentration and change from baseline in total Factor XI (FXI) concentrations(Up to 36 days)
- Absolute concentration and change from baseline in free FXI concentrations(Up to 36 days)
- Incidence of antidrug antibodies (ADAs) to REGN7508 over time(Up to 36 days)