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RE-THINc ESRD: 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

Sponsor
Bayer (Industry)
Overall Status
Completed
CT.gov ID
NCT04534114
Collaborator
(none)
307
Enrollment
71
Locations
4
Arms
20.2
Actual Duration (Months)
4.3
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
307 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 4, 2020
Actual Primary Completion Date :
Jan 24, 2022
Actual Study Completion Date :
May 12, 2022

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Pooled Placebo

Participants will be allocated at randomization to 1 of 3 dose cohorts 40 mg, 80 mg and 120 mg and within each cohort to receive subcutaneous treatment with either BAY2976217 or matching placebo.

Drug: Placebo
Matching placebo to BAY2976217 will be injected subcutaneously.
Experimental: 40 mg BAY2976217

Participants will be allocated at randomization to 1 of 3 dose cohorts 40 mg, 80 mg and 120 mg and within each cohort to receive subcutaneous treatment with either BAY2976217 or matching placebo.

Drug: BAY2976217
Study intervention will be injected subcutaneously.
Other Names:
  • Factor XI LICA

    		•
    Experimental: 80 mg BAY2976217

    Participants will be allocated at randomization to 1 of 3 dose cohorts 40 mg, 80 mg and 120 mg and within each cohort to receive subcutaneous treatment with either BAY2976217 or matching placebo.

    Drug: BAY2976217
    Study intervention will be injected subcutaneously.
    Other Names:
  • Factor XI LICA

    		•
    Experimental: 120 mg BAY2976217

    Participants will be allocated at randomization to 1 of 3 dose cohorts 40 mg, 80 mg and 120 mg and within each cohort to receive subcutaneous treatment with either BAY2976217 or matching placebo.

    Drug: BAY2976217
    Study intervention will be injected subcutaneously.
    Other Names:
  • Factor XI LICA

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of major bleeding and clinically-relevant non-major bleeding during the main treatment period and within the on-treatment time window [Up to 24 weeks]

      As assessed by blinded Central Independent Adjudication Committee (CIAC)

    Secondary Outcome Measures

    1. Incidence of composite of major bleeding and clinically-relevant non-major bleeding during the main and extended treatment periods and within the on-treatment time window [Up to 48 weeks]

      As assessed by blinded Central Independent Adjudication Committee (CIAC)

    2. Number of participants with treatment-emergent adverse events (TEAEs) during the main treatment period and within the on-treatment time window [Up to 24 weeks]

    3. Number of participants with TEAEs during the main and extended treatment periods and within the on-treatment time window [Up to 48 weeks]

    4. Number of participants with TEAEs during the main and extended treatment periods and until 20 weeks after the last study intervention dose [Up to 64 weeks]

    5. Number of participants with TEAEs categorized by severity during the main treatment period and within the on-treatment time window [Up to 24 weeks]

    6. Number of participants with TEAEs categorized by severity during the main and extended treatment periods and within the on-treatment time window [Up to 48 weeks]

    7. Number of participants with TEAEs categorized by severity during the main and extended treatment periods and until 20 weeks after the last study intervention dose [Up to 64 weeks]

    8. Trough concentrations (Ctrough) of three dose levels of BAY2976217 [At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)]

    9. Maximum change in FXI antigen levels during the main treatment period [Up to 24 weeks]

    10. Maximum change in FXI activity levels during the main treatment period [Up to 24 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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 mm3 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 BAY 2306001/ISIS 416858 and BAY 2976217/ 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Fresenius Kidney Care Clovis Clovis California United States 93611
    2 Desert Cities Dialysis-Amethyst & Desert Cities Dialysis Victorville California United States 92392
    3 Davita East Ft. Lauderdale Dialysis Center Fort Lauderdale Florida United States 33316
    4 Fresenius Kidney Care St. Louis Regional Dialysis Saint Ann Missouri United States 63074
    5 Chromalloy Dialysis Center Saint Louis Missouri United States 63110
    6 Fresenius Medical Care - Fire Mesa Dialysis Unit Las Vegas Nevada United States 89128
    7 DaVita Northwest Medical Center Dialysis San Antonio Texas United States 78229
    8 San Antonio Kidney Disease Center Physicians Group, PLLC San Antonio Texas United States 78258
    9 Salem VA Medical Center Salem Virginia United States 24153
    10 OL Vrouwziekenhuis - Campus Aalst Aalst Belgium 9300
    11 UZ Brussel Bruxelles - Brussel Belgium 1090
    12 UZ Antwerpen Edegem Belgium 2650
    13 Regionaal ZH Jan Yperman Campus Mariaziekenhuis Ieper Belgium 8900
    14 First Dialysis Services Bulgaria Ead Montana Bulgaria 3400
    15 MHAT Samokov Samokov Bulgaria 2000
    16 MHAT "Knyaginya Klementina - Sofia"EAD Sofia Bulgaria 1233
    17 MHAT National Cardiology Hospital EAD Sofia Bulgaria 1309
    18 Etobicoke General Hospital Etobicoke Ontario Canada M9V 1R8
    19 St. Joseph's Healthcare - Hamilton Hamilton Ontario Canada L8N 4A6
    20 Lakeridge Health-Oshawa Oshawa Ontario Canada L1G 2B9
    21 St. Michael's Hospital Toronto Ontario Canada M5B 1W8
    22 Centre de services ambulatoires de dialyse de Gaspé Montreal Quebec Canada H2T 3B3
    23 CHU de Québec-Université Laval Quebec Canada G1R 2J6
    24 Nemocnice Frydek-Mistek Frydek-Mistek Czechia 738 01
    25 Klatovska nemocnice Klatovy Czechia 339 01
    26 Fresenius Medical Care - DS, s.r.o. Melnik Czechia 276 01
    27 Oblastni nemocnice Mlada Boleslav Mlada Boleslav Czechia 293 50
    28 Robert-Bosch-Krankenhaus Stuttgart Baden-Württemberg Germany 70376
    29 DaVita Clinical Research Deutschland GmbH Düsseldorf Nordrhein-Westfalen Germany 40210
    30 DaVita Clinical Resarch Germany GmbH Geilenkirchen Nordrhein-Westfalen Germany 52511
    31 Nephrologisches Zentrum Hoyerswerda Hoyerswerda Sachsen Germany 02977
    32 Universitätsklinikum Schleswig-Holstein (UKSH) Kiel Schleswig-Holstein Germany 24105
    33 University General Hospital of Heraklion Heraklion Greece 711 10
    34 University General Hospital of Patra Patra Greece 26504
    35 PAPANIKOLAOU General Hospital Thessaloniki Pilea Chortiatis Greece 57010
    36 Bacs-Kiskun Megyei Korhaz Kalocsa Hungary 6300
    37 SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont Szeged Hungary 6720
    38 Matsunami General Hospital Hashima-gun Gifu Japan 501-6062
    39 Sapporo Tokushukai Hospital Sapporo Hokkaido Japan 004-0041
    40 Ibaraki Prefectural Central Hospital Kasama Ibaraki Japan 309-1793
    41 Public Central Hospital of Matto Ishikawa Hakusan Ishikawa Japan 924-8588
    42 Shonan Fujisawa Tokushukai Hospital Fujisawa Kanagawa Japan 251-0041
    43 Hanyu General Hospital Hanyu Saitama Japan 348-0045
    44 Medical corporation association Shunshin-kai Inage hospital Chiba Japan 263-0043
    45 The Catholic University of Korea, Incheon St.Mary's Hospital Incheon Incheon Gwang''yeogsi Korea, Republic of 21431
    46 Yeouido St. Mary's Hospital Seoul Seoul Teugbyeolsi Korea, Republic of 150-713
    47 Daugavpils Regional Hospital Daugavpils Latvia LV-5417
    48 Liepaja Regional Hospital Liepaja Latvia LV-3414
    49 P. Stradins Clinical University Hospital Riga Latvia LV-1002
    50 Vidzemes Hospital Valmiera Latvia LV-4201
    51 High Technology Center Clinic 1 Moscow Russian Federation 125466
    52 Limited Liability Company "Nefroline-Novosibirsk" Novosibirsk Russian Federation 630064
    53 LLC Frezenius Nefrocare Penza Russian Federation 440034
    54 LLC Dialysis center Podolsk Russian Federation 142110
    55 Nikiforov All-Russian Center of Emergency and Radiation Med Saint-Petersburg Russian Federation 197374
    56 Botkin clinical infectious diseases hospital St. Petersburg Russian Federation 195067
    57 LLC B. Brown Avitum Russland Clinics St. Petersburg Russian Federation 196247
    58 State Budgetary Healthcare Institution City Hospital #26 St. Petersburg Russian Federation 196247
    59 Ciutat Sanitària i Universitària de Bellvitge L'Hospitalet de Llobregat Barcelona Spain 08907
    60 Hospital Principe de Asturias Alcalá de Henares Madrid Spain 28805
    61 Hospital Clínic i Provincial de Barcelona Barcelona Spain 08036
    62 Hospital Universitario Virgen de las Nieves|Nefrologia Granada Spain 18014
    63 Hospital Universitari i Politècnic La Fe Valencia Spain 46026
    64 Chi Mei Medical Center Tainan Taiwan 710
    65 Taipei Medical University Hospital Taipei Taiwan 110
    66 Medical Center Fresenius Medical Care Ukraine, LLC Chernigiv Ukraine 14034
    67 Kyiv City Center of Nephrology and Dialysis Kyiv Ukraine 01023
    68 Kyiv Regional Clinical Hospital Kyiv Ukraine 04107
    69 Regional Clinical Hospital - Odessa Odesa Ukraine 65025
    70 Ternopil University Hospital Ternopil Ukraine 46002
    71 Zaporizhia Municipal Clinical Hospital No.10 Zaporizhzhya Ukraine 69001

    Sponsors and Collaborators

    • Bayer

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bayer
    ClinicalTrials.gov Identifier:
    NCT04534114
    Other Study ID Numbers:
    • 21170
    • 2019-003927-39
    First Posted:
    Sep 1, 2020
    Last Update Posted:
    Jun 14, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Bayer
    End stage renal disease (ESRD)
    Hemodialysis (HD)
    Thrombotic Events
    Additional relevant MeSH terms:
    Kidney Diseases
    Kidney Failure, Chronic

    Study Results

    No Results Posted as of Jun 14, 2022