Study to Investigate the Safety of a Drug Called Osocimab at Low and High Doses in Adult Patients With Kidney Failure Requiring Regular Hemodialysis

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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End-stage Renal Disease, Prevention of Thromboembolic Events, Hemodialysis, Hemodiafiltration

Intervention / Treatment
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* Drug: BAY1213790 (Osocimab)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BAY1213790 low dose<br>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. | Drug: BAY1213790 (Osocimab)<br>* Single loading dose as subcutaneous abdominal injection followed by monthly maintenance doses.<br>|
| Placebo Comparator: Placebo low dose<br>Placebo will be administered subcutaneously in the same manner as Osocimab. | Drug: Placebo<br>* Subcutaneous administration in the same manner as Osocimab.<br>|
| Experimental: BAY1213790 high dose<br>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. | Drug: BAY1213790 (Osocimab)<br>* Single loading dose as subcutaneous abdominal injection followed by monthly maintenance doses.<br>|
| Experimental: Placebo high dose<br>Placebo will be administered subcutaneously in the same manner as Osocimab. | Drug: Placebo<br>* Subcutaneous administration in the same manner as Osocimab.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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. | 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 Composite of Moderate and Severe Adverse Events (AEs) and Serious Adverse Events (SAEs) | 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. | From the first dose of study intervention up until 30 days after last study intervention in the main treatment period, up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Activated Partial Thromboplastin Time (aPTT) at 6 Months Trough Levels Versus Baseline. | The aPTT at trough levels after 6 months were analyzed as ratio to baseline by providing the Geometric Mean (Standard Deviation). aPTT was measured via the kaolin-trigger method (clotting assay). | At 6 months (Visit 19 / Day 30 of the 6th month) | 
| Ratio of Factor XI (FXI) Activity at 6 Months Trough Levels Versus Baseline | The Factor XI (FXI) activity at trough levels after 6 months were analyzed as ratio to baseline by providing the Geometric Mean (Standard Deviation). Factor XI activity was assessed with an aPTT-based coagulation test using FXI deficient plasma. | At 6 months (Visit 19 / Day 30 of the 6th month) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End-stage renal disease (ESRD), Hemodialysis