Factor XI LICA to Reduce Thrombotic Events in End-Stage Renal Disease Patients on Hemodialysis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of BAY 2976217
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 307
- 试验地点
- 69
- 主要终点
- Incidence of Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) During the Main Treatment Period and Within the On-treatment Time Window, as Assessed by Blinded Central Independent Adjudication Committee (CIAC)
研究概览
简要总结
Patients whose kidneys are no longer able to work as they should and require treatment to filter wastes from the blood (hemodialysis) are at high risk for blood clots that form in blood vessels (thrombosis) blocking blood flow that causes heart attacks, strokes, and other life-threatening conditions. BAY2976217 is under clinical development for prevention of thrombosis. The goal of the study is to learn more about the safety of BAY2976217, how it is tolerated and the way the body absorbs, distributes and gets rid of the study dug given as multiple doses in participants with renal impairment who require hemodialysis.
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
- •Participant must be at least 18 years of age at the time of signing the informed consent form (ICF)
- •Participants with ESRD on hemodialysis (HD) for ≥3 months at the time of signing of the ICF, receiving dialysis at least 9 hours a week and stable in the view of the investigator
- •Male 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)
- •Capable of giving signed ICF as described in the Protocol, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
排除标准
- •Participants receiving antiplatelet therapy except daily acetylsalicylic acid (ASA) ≤ 150 mg/day
- •Participants receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure
- •Known inherited bleeding disorder e.g. von-Willebrand disease or Hemophilia A, B or C
- •Recent (<6 months before screening) clinically significant bleeding, or at high risk of bleeding (in the judgement of the investigator)
- •Recent (<3 months before screening) thromboembolic event, e.g. acute coronary syndrome, stroke, or Venous thromboembolism (except dialysis access thrombosis)
- •Recent (<3 months before screening) major surgery or scheduled major surgery during participation in the study
- •Scheduled living donor renal transplant during study participation
- •Known Hepatitis B or C
- •Known HIV with recent documented detectable viral load (<3 months before screening)
- •Persistent heart failure as classified by the New York Heart Association classification of 3 or higher
- •Life expectancy less than 6 months
- •Sustained uncontrolled hypertension (persistent measurements of diastolic blood pressure ≥ 100 mmHg, and/or systolic blood pressure ≥ 180 mmHg)
- •Hepatic disease associated with either: coagulopathy leading to a clinically relevant bleeding risk, or ALT > 3x ULN, or total bilirubin >2x ULN with direct bilirubin > 20% of the total
- •Hb < 9.0 g/dL at screening
- •Platelet count < 120,000 mm^3 at screening
- •Known hypersensitivity to the investigational drug or to inactive constituents of the study intervention
- •Active malignancy requiring treatment during study participation (except non-melanoma skin cancer, or cervical carcinoma in situ)
- •Participation in a study with an investigational medicinal product within 30 days or within 5 half-lives of the previous administered drug, whichever is longer, prior to the screening/observational period (Note: Participants from previous BAY2306001/ISIS 416858 and BAY2976217/ ION 957943 studies are eligible)
- •Any other conditions, which, in the opinion of the investigator or Sponsor would make the subject unsuitable for inclusion
- •Confirmed pregnancy
研究组 & 干预措施
Pooled Placebo
Participants received subcutaneous treatment with matching placebo.
干预措施: Placebo (Drug)
40 mg BAY2976217
Participants received subcutaneous treatment with 40 mg BAY2976217.
干预措施: Fesomersen sodium (BAY2976217) (Drug)
80 mg BAY2976217
Participants received subcutaneous treatment with 80 mg BAY2976217.
干预措施: Fesomersen sodium (BAY2976217) (Drug)
120 mg BAY2976217
Participants received subcutaneous treatment with 120 mg BAY2976217.
干预措施: Fesomersen sodium (BAY2976217) (Drug)
结局指标
主要结局
Incidence of Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) During the Main Treatment Period and Within the On-treatment Time Window, as Assessed by Blinded Central Independent Adjudication Committee (CIAC)
时间窗: Up to 24 weeks
MB is defined as symptomatic bleeding and: 1) Fatal bleeding, and/or; 2) Bleeding in a critical area or organ, such as intracranial, intraspinal, intraocular, retroperitoneal, intraarticular or pericardial, or intramuscular with compartment syndrome, and/or; 3) Bleeding causing a fall in hemoglobin level of 20 g/L (2.0 g/dL) (1.24 mmol/L) or more, or leading to transfusion of two or more units of whole blood or red cells. CRNMB is defined as any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding but does meet at least one of the following criteria: 1) Requiring medical intervention by a healthcare professional; 2) Leading to hospitalization or increased level of care; 3) Prompting a face-to-face evaluation. n/100 person-years: number of subjects with incident events divided by the cumulative at-risk time in the reference population, where a subject is no longer at risk once an incident event occurred.
次要结局
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity(Up to 24 weeks)
- Maximum Change in FXI Activity Levels During the Main Treatment Period(Baseline, Days 1 (Pre-Dose and 5 hours post-dose), 2, 8, 15, 22, 29 (Pre-dose and 5 hours post-dose), 43, 57 (Pre-dose), 71, 85 (Pre-dose), 113 (Pre-dose), 141 (Pre-dose),148, 155, 162, and 169 (Pre-dose))
- Incidence of Composite of MB and CRNMB During the Main and Extended Treatment Periods and Within the On-treatment Time Window, as Assessed by Blinded CIAC(Up to 48 weeks)
- Number of Participants With TEAEs During the Main and Extended Treatment Periods and Until 20 Weeks After the Last Study Intervention Dose and Their Severity(Up to 48 weeks)
- Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity(Up to 48 weeks)
- Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen(At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141))
- Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period(Up to 24 weeks)