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

NCT04534114 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 211702019-003927-39
• Study Type: interventional
• Target: 307
• Locations: 15 countries
• Sites: 69

Brief Summary

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.

Conditions

End Stage Renal Disease Requiring Hemodialysis

Keywords

End stage renal disease (ESRD); Hemodialysis (HD); Thrombotic Events

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• 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 Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity

  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

  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

• Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen

  At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)

Study Arms (4)

Pooled Placebo

PLACEBO COMPARATOR

Participants received subcutaneous treatment with matching placebo.

Drug: Placebo

40 mg BAY2976217

EXPERIMENTAL

Participants received subcutaneous treatment with 40 mg BAY2976217.

Drug: Fesomersen sodium (BAY2976217)

80 mg BAY2976217

EXPERIMENTAL

Participants received subcutaneous treatment with 80 mg BAY2976217.

Drug: Fesomersen sodium (BAY2976217)

120 mg BAY2976217

EXPERIMENTAL

Participants received subcutaneous treatment with 120 mg BAY2976217.

Drug: Fesomersen sodium (BAY2976217)

Interventions

Fesomersen sodium (BAY2976217) DRUG

Study intervention will be injected subcutaneously.

Also known as: Factor XI LICA

120 mg BAY2976217; 40 mg BAY2976217; 80 mg BAY2976217

Placebo DRUG

Matching placebo to BAY2976217 will be injected subcutaneously.

Pooled Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (69)

Fresenius Kidney Care Clovis

Clovis, California, 93611, United States

Location

Desert Cities Dialysis-Amethyst & Desert Cities Dialysis

Victorville, California, 92392, United States

Location

Davita East Ft. Lauderdale Dialysis Center

Fort Lauderdale, Florida, 33316, United States

Location

Fresenius Kidney Care St. Louis Regional Dialysis

Saint Ann, Missouri, 63074, United States

Location

Chromalloy Dialysis Center

St Louis, Missouri, 63110, United States

Location

Fresenius Medical Care - Fire Mesa Dialysis Unit

Las Vegas, Nevada, 89128, United States

Location

DaVita Northwest Medical Center Dialysis

San Antonio, Texas, 78229, United States

Location

San Antonio Kidney Disease Center Physicians Group, PLLC

San Antonio, Texas, 78258, United States

Location

Salem VA Medical Center

Salem, Virginia, 24153, United States

Location

OL Vrouwziekenhuis - Campus Aalst

Aalst, 9300, Belgium

Location

UZ Brussel

Bruxelles - Brussel, 1090, Belgium

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

Regionaal ZH Jan Yperman Campus Mariaziekenhuis

Ieper, 8900, Belgium

Location

First Dialysis Services Bulgaria Ead

Montana, 3400, Bulgaria

Location

MHAT Samokov

Samokov, 2000, Bulgaria

Location

MHAT "Knyaginya Klementina - Sofia"EAD

Sofia, 1233, Bulgaria

Location

MHAT National Cardiology Hospital EAD

Sofia, 1309, Bulgaria

Location

Etobicoke General Hospital

Etobicoke, Ontario, M9V 1R8, Canada

Location

St. Joseph's Healthcare - Hamilton

Hamilton, Ontario, L8N 4A6, Canada

Location

Lakeridge Health-Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

Unity Health Toronto: St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Centre de services ambulatoires de dialyse de Gaspé

Montreal, Quebec, H2T 3B3, Canada

Location

CHU de Québec-Université Laval

Québec, G1J 1Z4, Canada

Location

Nemocnice Frydek-Mistek

Frýdek-Místek, 738 01, Czechia

Location

Klatovska nemocnice

Klatovy, 339 01, Czechia

Location

Fresenius Medical Care - DS, s.r.o.

Mělník, 276 01, Czechia

Location

Oblastni nemocnice Mlada Boleslav

Mladá Boleslav, 293 50, Czechia

Location

DaVita Clinical Research Deutschland GmbH

Düsseldorf, North Rhine-Westphalia, 40210, Germany

Location

DaVita Clinical Resarch Germany GmbH

Geilenkirchen, North Rhine-Westphalia, 52511, Germany

Location

Universitätsklinikum Schleswig-Holstein (UKSH)

Kiel, Schleswig-Holstein, 24105, Germany

Location

University General Hospital of Heraklion

Heraklion, 711 10, Greece

Location

University General Hospital of Patra

Pátrai, 26504, Greece

Location

PAPANIKOLAOU General Hospital Thessaloniki

Pilea Chortiatis, 57010, Greece

Location

Bacs-Kiskun Megyei Korhaz

Kalocsa, 6300, Hungary

Location

SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont

Szeged, 6720, Hungary

Location

Matsunami General Hospital

Hashima-gun, Gifu, 501-6062, Japan

Location

Sapporo Tokushukai Hospital

Sapporo, Hokkaido, 004-0041, Japan

Location

Ibaraki Prefectural Central Hospital

Kasama, Ibaraki, 309-1793, Japan

Location

Public Central Hospital of Matto Ishikawa

Hakusan, Ishikawa-ken, 924-8588, Japan

Location

Shonan Fujisawa Tokushukai Hospital

Fujisawa, Kanagawa, 251-0041, Japan

Location

Hanyu General Hospital

Hanyū, Saitama, 348-0045, Japan

Location

Medical corporation association Shunshin-kai Inage hospital

Chiba, 263-0043, Japan

Location

Daugavpils Regional Hospital

Daugavpils, LV-5417, Latvia

Location

Liepaja Regional Hospital

Liepāja, LV-3414, Latvia

Location

P. Stradins Clinical University Hospital

Riga, LV-1002, Latvia

Location

Vidzemes Hospital

Valmiera, LV-4201, Latvia

Location

High Technology Center Clinic 1

Moscow, 125466, Russia

Location

Limited Liability Company "Nefroline-Novosibirsk"

Novosibirsk, 630064, Russia

Location

LLC Frezenius Nefrocare

Penza, 440034, Russia

Location

LLC Dialysis center

Podolsk, 142110, Russia

Location

Botkin clinical infectious diseases hospital

Saint Petersburg, 195067, Russia

Location

LLC B. Brown Avitum Russland Clinics

Saint Petersburg, 196247, Russia

Location

State Budgetary Healthcare Institution City Hospital #26

Saint Petersburg, 196247, Russia

Location

Nikiforov All-Russian Center of Emergency and Radiation Med

Saint Petersburg, 197374, Russia

Location

The Catholic University of Korea, Incheon St.Mary's Hospital

Incheon, Incheon Gwang''yeogsi, 21431, South Korea

Location

Yeouido St. Mary's Hospital

Seoul, Seoul Teugbyeolsi, 150-713, South Korea

Location

Hospital Principe de Asturias

Alcalá de Henares, Madrid, 28805, Spain

Location

Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention

Barcelona, 08907, Spain

Location

Hospital Clínic i Provincial de Barcelona

Barcelona, 8036, Spain

Location

Hospital Universitario Virgen de las Nieves|Nefrologia

Granada, 18014, Spain

Location

Hospital Universitari i Politècnic La Fe | Nefrología

Valencia, 46026, Spain

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

Taipei Medical University Hospital

Taipei, 110, Taiwan

Location

Medical Center Fresenius Medical Care Ukraine, LLC

Chernihiv, 14034, Ukraine

Location

Kyiv City Center of Nephrology and Dialysis

Kyiv, 01023, Ukraine

Location

Kyiv Regional Clinical Hospital

Kyiv, 04107, Ukraine

Location

Regional Clinical Hospital - Odessa

Odesa, 65025, Ukraine

Location

Ternopil Regional Clinical Hospital

Ternopil, 46002, Ukraine

Location

Zaporizhia Municipal Clinical Hospital No.10

Zaporizhzhya, 69001, Ukraine

Location

Related Publications (2)

• Stamellou E, Noels H, Floege J. Factor XI inhibition in hemodialysis patients: the safer anticoagulation? Kidney Int. 2024 Jul;106(1):21-23. doi: 10.1016/j.kint.2024.03.029.

  PMID: 38906653 DERIVED

• Winkelmayer WC, Lensing AWA, Thadhani RI, Mahaffey KW, Walsh M, Pap AF, Willmann S, Thelen K, Hodge S, Solms A, Ingham SJM, Eikelboom J; RE-THINC investigators. A Phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis. Kidney Int. 2024 Jul;106(1):145-153. doi: 10.1016/j.kint.2024.02.024. Epub 2024 Mar 26.

  PMID: 38537676 DERIVED

Related 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.

MeSH Terms

Conditions

Kidney Failure, Chronic

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer AG

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2020
• First Posted: September 1, 2020
• Study Start: September 4, 2020
• Primary Completion: January 24, 2022
• Study Completion: May 12, 2022
• Last Updated: July 3, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); US (9); BE (4); CA (6); ES (5); HU (2); JP (7); CZ (4); GR (3); BU (4); RU (8); KR (2); TW (2); UA (6); LA (4)