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)

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

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.

Study Overview

• Status: Completed
• Conditions: End Stage Renal Disease Requiring Hemodialysis
• Intervention / Treatment: Drug: Placebo; Drug: Fesomersen sodium (BAY2976217)

• Study Type: Interventional
• Enrollment (Actual): 307
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium, 9300
    • OL Vrouwziekenhuis - Campus Aalst
  • Bruxelles - Brussel, Belgium, 1090
    • UZ Brussel
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Ieper, Belgium, 8900
    • Regionaal ZH Jan Yperman Campus Mariaziekenhuis
• Bulgaria
  • Montana, Bulgaria, 3400
    • First Dialysis Services Bulgaria Ead
  • Samokov, Bulgaria, 2000
    • MHAT Samokov
  • Sofia, Bulgaria, 1309
    • MHAT National Cardiology Hospital EAD
  • Sofia, Bulgaria, 1233
    • MHAT "Knyaginya Klementina - Sofia"EAD
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Quebec-Universite Laval
  • Ontario
    • Etobicoke, Ontario, Canada, M9V 1R8
      • Etobicoke General Hospital
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare - Hamilton
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health-Oshawa
    • Toronto, Ontario, Canada, M5B 1W8
      • Unity Health Toronto: St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2T 3B3
      • Centre de services ambulatoires de dialyse de Gaspé
• Czechia
  • Frydek-Mistek, Czechia, 738 01
    • Nemocnice Frydek-Mistek
  • Klatovy, Czechia, 339 01
    • Klatovska nemocnice
  • Melnik, Czechia, 276 01
    • Fresenius Medical Care - DS, s.r.o.
  • Mlada Boleslav, Czechia, 293 50
    • Oblastni nemocnice Mlada Boleslav
• Germany
  • Nordrhein-Westfalen
    • Duesseldorf, Nordrhein-Westfalen, Germany, 40210
      • DaVita Clinical Research Deutschland GmbH
    • Geilenkirchen, Nordrhein-Westfalen, Germany, 52511
      • DaVita Clinical Resarch Germany GmbH
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105
      • Universitatsklinikum Schleswig-Holstein (UKSH)
• Greece
  • Heraklion, Greece, 711 10
    • University General Hospital of Heraklion
  • Patra, Greece, 26504
    • University General Hospital of Patra
  • Pilea Chortiatis, Greece, 57010
    • PAPANIKOLAOU General Hospital Thessaloniki
• Hungary
  • Kalocsa, Hungary, 6300
    • Bacs-kiskun Megyei Korhaz
  • Szeged, Hungary, 6720
    • SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
• Japan
  • Chiba, Japan, 263-0043
    • Medical corporation association Shunshin-kai Inage hospital
  • Gifu
    • Hashima-gun, Gifu, Japan, 501-6062
      • Matsunami General Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 004-0041
      • Sapporo Tokushukai Hospital
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital
  • Ishikawa
    • Hakusan, Ishikawa, Japan, 924-8588
      • Public Central Hospital of Matto Ishikawa
  • Kanagawa
    • Fujisawa, Kanagawa, Japan, 251-0041
      • Shonan Fujisawa Tokushukai Hospital
  • Saitama
    • Hanyu, Saitama, Japan, 348-0045
      • Hanyu General Hospital
• Korea, Republic of
  • Incheon Gwang''yeogsi
    • Incheon, Incheon Gwang''yeogsi, Korea, Republic of, 21431
      • The Catholic University of Korea, Incheon St.Mary's Hospital
  • Seoul Teugbyeolsi
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 150-713
      • Yeouido St. Mary's Hospital
• Latvia
  • Daugavpils, Latvia, LV-5417
    • Daugavpils Regional Hospital
  • Liepaja, Latvia, LV-3414
    • Liepaja Regional Hospital
  • Riga, Latvia, LV-1002
    • P. Stradins Clinical University Hospital
  • Valmiera, Latvia, LV-4201
    • Vidzemes Hospital
• Russian Federation
  • Moscow, Russian Federation, 125466
    • High Technology Center Clinic 1
  • Novosibirsk, Russian Federation, 630064
    • Limited Liability Company "Nefroline-Novosibirsk"
  • Penza, Russian Federation, 440034
    • LLC Frezenius Nefrocare
  • Podolsk, Russian Federation, 142110
    • LLC Dialysis center
  • Saint-Petersburg, Russian Federation, 197374
    • Nikiforov All-Russian Center of Emergency and Radiation Med
  • St. Petersburg, Russian Federation, 195067
    • Botkin clinical infectious diseases hospital
  • St. Petersburg, Russian Federation, 196247
    • LLC B. Brown Avitum Russland Clinics
  • St. Petersburg, Russian Federation, 196247
    • State Budgetary Healthcare Institution City Hospital #26
• Spain
  • Barcelona, Spain, 8036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves|Nefrologia
  • Valencia, Spain, 46026
    • Hospital Universitari i Politècnic La Fe | Nefrología
  • Madrid
    • Alcalá de Henares, Madrid, Spain, 28805
      • Hospital Principe de Asturias
• Taiwan
  • Tainan, Taiwan, 710
    • Chi Mei Medical Center
  • Taipei, Taiwan, 110
    • Taipei Medical University Hospital
• Ukraine
  • Chernigiv, Ukraine, 14034
    • Medical Center Fresenius Medical Care Ukraine, LLC
  • Kyiv, Ukraine, 04107
    • Kyiv Regional Clinical Hospital
  • Kyiv, Ukraine, 01023
    • Kyiv City Center of Nephrology and Dialysis
  • Odesa, Ukraine, 65025
    • Regional Clinical Hospital - Odessa
  • Ternopil, Ukraine, 46002
    • Ternopil Regional Clinical Hospital
  • Zaporizhzhya, Ukraine, 69001
    • Zaporizhia Municipal Clinical Hospital No.10
• United States
  • California
    • Clovis, California, United States, 93611
      • Fresenius Kidney Care Clovis
    • Victorville, California, United States, 92392
      • Desert Cities Dialysis-Amethyst & Desert Cities Dialysis
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Davita East Ft. Lauderdale Dialysis Center
  • Missouri
    • Saint Ann, Missouri, United States, 63074
      • Fresenius Kidney Care St. Louis Regional Dialysis
    • Saint Louis, Missouri, United States, 63110
      • Chromalloy Dialysis Center
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Fresenius Medical Care - Fire Mesa Dialysis Unit
  • Texas
    • San Antonio, Texas, United States, 78229
      • DaVita Northwest Medical Center Dialysis
    • San Antonio, Texas, United States, 78258
      • San Antonio Kidney Disease Center Physicians Group, PLLC
  • Virginia
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Pooled Placebo; Participants received subcutaneous treatment with matching placebo.	Drug: Placebo; Matching placebo to BAY2976217 will be injected subcutaneously.
Experimental: 40 mg BAY2976217; Participants received subcutaneous treatment with 40 mg BAY2976217.	Drug: Fesomersen sodium (BAY2976217); Study intervention will be injected subcutaneously.; Other Names: Factor XI LICA
Experimental: 80 mg BAY2976217; Participants received subcutaneous treatment with 80 mg BAY2976217.	Drug: Fesomersen sodium (BAY2976217); Study intervention will be injected subcutaneously.; Other Names: Factor XI LICA
Experimental: 120 mg BAY2976217; Participants received subcutaneous treatment with 120 mg BAY2976217.	Drug: Fesomersen sodium (BAY2976217); Study intervention will be injected subcutaneously.; Other Names: Factor XI LICA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	Up to 48 weeks
Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity	TEAEs were analyzed during the on-treatment time window within the main treatment period in the safety analysis set (SAF). Data observed from the randomization date until the end of the main treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration.	Up to 24 weeks
Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity	TEAEs were analyzed during during main and extended treatment periods in the safety analysis set (SAF). Data observed from the randomization date until the end of the extension treatment period. TEAEs were defined as events occurring after first study intervention administration and up to 20 weeks after last study intervention administration.	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	TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake.	Up to 48 weeks
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen	Trough (pre-dose) fesomersen-equivalent plasma concentrations (Ctrough) for 3 dose levels of fesomersen were summarized descriptively by dose level and visit: Visit 12, Visit 14, Visit 16, Visit 18 (main treatment period). Ctrough was not measured for the placebo group.	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	The secondary endpoint of change in FXI antigen levels during the main treatment period was an optional secondary endpoint only as mentioned in the integrated clinical protocol amendment version 3.0 and was not analyzed in this study as the FXI activity assay is sufficient to describe the effect on FXI level in plasma.	Up to 24 weeks
Maximum Change in FXI Activity Levels During the Main Treatment Period	The FXIa activity was measured by a fluorogenic activated FXIa activity (AXIA) assay. Absolute change from baseline at each visit until Visit 22 (Day 169) are reported.	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)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
• Click here to find information about studies related to Bayer AG products conducted in Europe.

Study record dates

Study Major Dates

• Study Start (Actual): September 4, 2020
• Primary Completion (Actual): January 24, 2022
• Study Completion (Actual): May 12, 2022

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 30, 2020
• First Posted (Actual): September 1, 2020

Study Record Updates

• Last Update Posted (Actual): July 3, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Hemodialysis (HD); End stage renal disease (ESRD); Thrombotic Events
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic
• Other Study ID Numbers: 21170; 2019-003927-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no current plans to share data. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No