A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multi-center Study to Assess the Safety and Tolerability of Monthly Subcutaneous Administrations of a Low and High Dose Cohort of Osocimab to ESRD Patients on Regular Hemodialysis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 704
- 试验地点
- 148
- 主要终点
- Cumulative Incidence Risk of the First Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) Events as Assessed by Blinded Central Independent Adjudication Committee (CIAC)
研究概览
简要总结
In this study researchers want to learn about the safety of drug Osocimab at lower-dose and higher-doses in adult participants with kidney disease undergoing regular dialysis (a procedure that uses a machine to get rid of toxins and extra fluids in the blood). Patients with kidney disease undergoing regular dialysis are at high risk for heart and blood vessels diseases. Osocimab is a human monoclonal antibody under development for the prevention of events caused by blood clots like heart attack, stroke and death due to heart or blood vessels diseases. It works by binding to and blocking the activated form of clotting factor XI which increases the formation and stability of clots. Researchers also want to find out how drug Osocimab works in human body and how the body absorbs, distributes and excretes the drug.
Participants in this study will receive monthly injection of either Osocimab at a lower-dose or higher-dose or placebo (a placebo looks like a treatment but does not have any medicine in it). Both Osocimab and placebo will be injected into the tissue under the skin of the belly. Observation for each participant will last up to 23 months. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
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
- Triple (Participant, 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
- •Participants must be at least 18 years of age
- •Patients with end-stage renal disease on hemodialysis (including hemodiafiltration) for ≥3 months, receiving dialysis at least 9 hours a week and stable in the view of the investigator
- •Body weight of at least 50 kg
- •Male and/or female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
排除标准
- •Recent (<6 months before screening) clinically significant bleeding
- •Hemoglobin (Hb) < 9.0 g/dL at screening
- •Platelet count < 100 x 10^9/L
- •aPTT or PT > ULN (upper limit of normal)
- •Hepatic disease associated with ALT > 3x ULN, or total bilirubin >2x ULN with direct bilirubin > 20% of the total
- •Sustained uncontrolled hypertension (diastolic blood pressure ≥100 mmHg and/or systolic blood pressure ≥ 180 mmHg)
- •Known intracranial neoplasm, arteriovenous malformation or aneurysm
- •Known bleeding disorders e.g. von-Willebrand disease or Hemophilia A, B or C
- •Recent (<3 months before screening) thromboembolic event, e.g. acute coronary syndrome, stroke or VTE (except dialysis access thrombosis)
- •Recent (<3 months before screening) major surgery or scheduled major surgery during study participation
- •Scheduled living donor renal transplant during study participation
- •Persistent heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher
- •Receiving antiplatelet therapy except daily ASA ≤ 150 mg/day
- •Receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure
研究组 & 干预措施
BAY1213790 low dose
Participants will receive Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg until the end of the extension treatment period.
干预措施: BAY1213790 (Osocimab) (Drug)
Placebo low dose
Placebo will be administered subcutaneously in the same manner as Osocimab.
干预措施: Placebo (Drug)
BAY1213790 high dose
Participants will receive Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg until the end of the extension treatment period.
干预措施: BAY1213790 (Osocimab) (Drug)
Placebo high dose
Placebo will be administered subcutaneously in the same manner as Osocimab.
干预措施: Placebo (Drug)
结局指标
主要结局
Cumulative Incidence Risk of the First Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) Events as Assessed by Blinded Central Independent Adjudication Committee (CIAC)
时间窗: From the first dose of study intervention up till 30 days after last study intervention in the main treatment period, up to 6 months
Cumulative incidence risk of the first Composite of MB and CRNMB (ISTH) at month 6 is reported in the table. Descriptive time to composite of MB and CRNMB Events is reported in statistical analysis. Descriptive time to composite of treatment emergent major and CRNMB events \[in alignment with International Society on Thrombosis and Haemostatsis (ISTH) guidelines\] analyses were performed. The cumulative incidence function for the event-of-interest together with the corresponding confidence interval were estimated for each treatment arm using Aalen-Johansen estimators. Cumulative incidence of events up to the day, inclusive.
Cumulative Incidence Risk of Composite of Moderate and Severe Adverse Events (AEs) and Serious Adverse Events (SAEs)
时间窗: From the first dose of study intervention up until 30 days after last study intervention in the main treatment period, up to 6 months
Cumulative incidence risk of composite of moderate and severe AEs and SAEs at month 6 is reported in the table. Descriptive time to the composite of Moderate and Severe AEs and SAEs is reported in statistical analysis. An AE was any untoward medical occurrence in a patient or clinical study participant, whether or not considered related to the study intervention.
次要结局
- Ratio of Activated Partial Thromboplastin Time (aPTT) at 6 Months Trough Levels Versus Baseline.(At 6 months (Visit 19 / Day 30 of the 6th month))
- Ratio of Factor XI (FXI) Activity at 6 Months Trough Levels Versus Baseline(At 6 months (Visit 19 / Day 30 of the 6th month))