Factor XI LICA to Reduce Events Such as Heart Attack and Stroke in Patients Whose Kidneys Are no Longer Able to Work as They Should and Require Treatment to Filter Wastes From the Blood: Focus is on the Safety of BAY2976217 and the Way the Body Absorbs, Distributes and Removes the Study Drug (RE-THINc ESRD)

Bayer

Status and phase: Completed; Phase 2

Conditions: End Stage Renal Disease Requiring Hemodialysis

Treatments: Drug: Placebo; Drug: Fesomersen sodium (BAY2976217)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04534114

21170

2019-003927-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 307 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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307 participants in 4 patient groups, including a placebo group

Pooled Placebo

Placebo Comparator group

Description:

Participants received subcutaneous treatment with matching placebo.

Treatment:

Drug: Placebo

40 mg BAY2976217

Experimental group

Description:

Participants received subcutaneous treatment with 40 mg BAY2976217.

Treatment:

Drug: Fesomersen sodium (BAY2976217)

80 mg BAY2976217

Experimental group

Description:

Participants received subcutaneous treatment with 80 mg BAY2976217.

Treatment:

Drug: Fesomersen sodium (BAY2976217)

120 mg BAY2976217

Experimental group

Description:

Participants received subcutaneous treatment with 120 mg BAY2976217.

Treatment:

Drug: Fesomersen sodium (BAY2976217)