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
- Conditions
- End Stage Renal Disease Requiring Hemodialysis
- Interventions
- Drug: Fesomersen sodium (BAY2976217)Drug: Placebo
- Registration Number
- NCT04534114
- Lead Sponsor
- Bayer
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 307
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 40 mg BAY2976217 Fesomersen sodium (BAY2976217) Participants received subcutaneous treatment with 40 mg BAY2976217. Pooled Placebo Placebo Participants received subcutaneous treatment with matching placebo. 80 mg BAY2976217 Fesomersen sodium (BAY2976217) Participants received subcutaneous treatment with 80 mg BAY2976217. 120 mg BAY2976217 Fesomersen sodium (BAY2976217) Participants received subcutaneous treatment with 120 mg BAY2976217.
- Primary Outcome Measures
Name Time Method 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) Up to 24 weeks 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.
- Secondary Outcome Measures
Name Time Method 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 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.
Maximum Change in FXI Activity Levels During the Main Treatment Period 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) 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.
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 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.
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 TEAEs occurring from first study intervention intake until 20 weeks after last study intervention intake.
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 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.
Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141) 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.
Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period Up to 24 weeks 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.
Trial Locations
- Locations (69)
Unity Health Toronto: St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Desert Cities Dialysis-Amethyst & Desert Cities Dialysis
🇺🇸Victorville, California, United States
Fresenius Kidney Care Clovis
🇺🇸Clovis, California, United States
Fresenius Kidney Care St. Louis Regional Dialysis
🇺🇸Saint Ann, Missouri, United States
Davita East Ft. Lauderdale Dialysis Center
🇺🇸Fort Lauderdale, Florida, United States
Chromalloy Dialysis Center
🇺🇸Saint Louis, Missouri, United States
Salem VA Medical Center
🇺🇸Salem, Virginia, United States
OL Vrouwziekenhuis - Campus Aalst
🇧🇪Aalst, Belgium
UZ Brussel
🇧🇪Bruxelles - Brussel, Belgium
First Dialysis Services Bulgaria Ead
🇧🇬Montana, Bulgaria
MHAT National Cardiology Hospital EAD
🇧🇬Sofia, Bulgaria
Etobicoke General Hospital
🇨🇦Etobicoke, Ontario, Canada
St. Joseph's Healthcare - Hamilton
🇨🇦Hamilton, Ontario, Canada
Lakeridge Health-Oshawa
🇨🇦Oshawa, Ontario, Canada
CHU de Québec-Université Laval
🇨🇦Quebec, Canada
Nemocnice Frydek-Mistek
🇨🇿Frydek-Mistek, Czechia
Fresenius Medical Care - Fire Mesa Dialysis Unit
🇺🇸Las Vegas, Nevada, United States
DaVita Northwest Medical Center Dialysis
🇺🇸San Antonio, Texas, United States
San Antonio Kidney Disease Center Physicians Group, PLLC
🇺🇸San Antonio, Texas, United States
Klatovska nemocnice
🇨🇿Klatovy, Czechia
Oblastni nemocnice Mlada Boleslav
🇨🇿Mlada Boleslav, Czechia
Universitätsklinikum Schleswig-Holstein (UKSH)
🇩🇪Kiel, Schleswig-Holstein, Germany
Fresenius Medical Care - DS, s.r.o.
🇨🇿Melnik, Czechia
DaVita Clinical Research Deutschland GmbH
🇩🇪Duesseldorf, Nordrhein-Westfalen, Germany
DaVita Clinical Resarch Germany GmbH
🇩🇪Geilenkirchen, Nordrhein-Westfalen, Germany
University General Hospital of Heraklion
🇬🇷Heraklion, Greece
University General Hospital of Patra
🇬🇷Patra, Greece
PAPANIKOLAOU General Hospital Thessaloniki
🇬🇷Pilea Chortiatis, Greece
Bacs-Kiskun Megyei Korhaz
🇭🇺Kalocsa, Hungary
Ibaraki Prefectural Central Hospital
🇯🇵Kasama, Ibaraki, Japan
Matsunami General Hospital
🇯🇵Hashima-gun, Gifu, Japan
SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
🇭🇺Szeged, Hungary
Sapporo Tokushukai Hospital
🇯🇵Sapporo, Hokkaido, Japan
Public Central Hospital of Matto Ishikawa
🇯🇵Hakusan, Ishikawa, Japan
The Catholic University of Korea, Incheon St.Mary's Hospital
🇰🇷Incheon, Incheon Gwang''yeogsi, Korea, Republic of
Yeouido St. Mary's Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
P. Stradins Clinical University Hospital
🇱🇻Riga, Latvia
Vidzemes Hospital
🇱🇻Valmiera, Latvia
High Technology Center Clinic 1
🇷🇺Moscow, Russian Federation
Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention
🇪🇸Barcelona, Spain
Hospital Principe de Asturias
🇪🇸Alcalá de Henares, Madrid, Spain
Hospital Clínic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Virgen de las Nieves|Nefrologia
🇪🇸Granada, Spain
Taipei Medical University Hospital
🇨🇳Taipei, Taiwan
Hospital Universitari i Politècnic La Fe | Nefrología
🇪🇸Valencia, Spain
Medical Center Fresenius Medical Care Ukraine, LLC
🇺🇦Chernigiv, Ukraine
Ternopil Regional Clinical Hospital
🇺🇦Ternopil, Ukraine
Kyiv City Center of Nephrology and Dialysis
🇺🇦Kyiv, Ukraine
Regional Clinical Hospital - Odessa
🇺🇦Odesa, Ukraine
MHAT "Knyaginya Klementina - Sofia"EAD
🇧🇬Sofia, Bulgaria
Daugavpils Regional Hospital
🇱🇻Daugavpils, Latvia
LLC B. Brown Avitum Russland Clinics
🇷🇺St. Petersburg, Russian Federation
Chi Mei Medical Center
🇨🇳Tainan, Taiwan
Medical corporation association Shunshin-kai Inage hospital
🇯🇵Chiba, Japan
Botkin clinical infectious diseases hospital
🇷🇺St. Petersburg, Russian Federation
State Budgetary Healthcare Institution City Hospital #26
🇷🇺St. Petersburg, Russian Federation
UZ Antwerpen
🇧🇪Edegem, Belgium
MHAT Samokov
🇧🇬Samokov, Bulgaria
Shonan Fujisawa Tokushukai Hospital
🇯🇵Fujisawa, Kanagawa, Japan
Hanyu General Hospital
🇯🇵Hanyu, Saitama, Japan
LLC Frezenius Nefrocare
🇷🇺Penza, Russian Federation
Nikiforov All-Russian Center of Emergency and Radiation Med
🇷🇺Saint-Petersburg, Russian Federation
Regionaal ZH Jan Yperman Campus Mariaziekenhuis
🇧🇪Ieper, Belgium
Liepaja Regional Hospital
🇱🇻Liepaja, Latvia
Limited Liability Company "Nefroline-Novosibirsk"
🇷🇺Novosibirsk, Russian Federation
Centre de services ambulatoires de dialyse de Gaspé
🇨🇦Montreal, Quebec, Canada
LLC Dialysis center
🇷🇺Podolsk, Russian Federation
Kyiv Regional Clinical Hospital
🇺🇦Kyiv, Ukraine
Zaporizhia Municipal Clinical Hospital No.10
🇺🇦Zaporizhzhya, Ukraine