Clinical trial NCT04534114: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: End Stage Renal Disease Requiring Hemodialysis
Keywords: End stage renal disease (ESRD)
Hemodialysis (HD)
Thrombotic Events
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-09-01
Enrollment: 307
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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)
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: 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
timeFrame: Up to 48 weeks
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Main Treatment Period and Within the On-treatment Time Window and Their Severity
timeFrame: Up to 24 weeks
measure: Number of Participants With TEAEs During the Main and Extended Treatment Periods and Within the On-treatment Time Window and Their Severity
timeFrame: Up to 48 weeks
measure: 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
timeFrame: Up to 48 weeks
measure: Trough Concentrations (Ctrough) of Three Dose Levels of Fesomersen
timeFrame: At visits V12 (Day 57), V14 (Day 85), V16 (Day 113), V18 (Day 141)
measure: Maximum Change in FXI (Coagulation Factor XI) Antigen Levels During the Main Treatment Period
timeFrame: Up to 24 weeks
measure: Maximum Change in FXI Activity Levels During the Main Treatment Period
timeFrame: 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)
Other outcomes:
Locations:
city: Clovis
country: United States
facility: Fresenius Kidney Care Clovis
state: California
city: Victorville
country: United States
facility: Desert Cities Dialysis-Amethyst & Desert Cities Dialysis
state: California
city: Fort Lauderdale
country: United States
facility: Davita East Ft. Lauderdale Dialysis Center
state: Florida
city: Saint Ann
country: United States
facility: Fresenius Kidney Care St. Louis Regional Dialysis
state: Missouri
city: Saint Louis
country: United States
facility: Chromalloy Dialysis Center
state: Missouri
city: Las Vegas
country: United States
facility: Fresenius Medical Care - Fire Mesa Dialysis Unit
state: Nevada
city: San Antonio
country: United States
facility: DaVita Northwest Medical Center Dialysis
state: Texas
city: San Antonio
country: United States
facility: San Antonio Kidney Disease Center Physicians Group, PLLC
state: Texas
city: Salem
country: United States
facility: Salem VA Medical Center
state: Virginia
city: Aalst
country: Belgium
facility: OL Vrouwziekenhuis - Campus Aalst
city: Bruxelles - Brussel
country: Belgium
facility: UZ Brussel
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Ieper
country: Belgium
facility: Regionaal ZH Jan Yperman Campus Mariaziekenhuis
city: Montana
country: Bulgaria
facility: First Dialysis Services Bulgaria Ead
city: Samokov
country: Bulgaria
facility: MHAT Samokov
city: Sofia
country: Bulgaria
facility: MHAT "Knyaginya Klementina - Sofia"EAD
city: Sofia
country: Bulgaria
facility: MHAT National Cardiology Hospital EAD
city: Etobicoke
country: Canada
facility: Etobicoke General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: St. Joseph's Healthcare - Hamilton
state: Ontario
city: Oshawa
country: Canada
facility: Lakeridge Health-Oshawa
state: Ontario
city: Toronto
country: Canada
facility: Unity Health Toronto: St. Michael's Hospital
state: Ontario
city: Montreal
country: Canada
facility: Centre de services ambulatoires de dialyse de Gaspé
state: Quebec
city: Quebec
country: Canada
facility: CHU de Québec-Université Laval
city: Frydek-Mistek
country: Czechia
facility: Nemocnice Frydek-Mistek
city: Klatovy
country: Czechia
facility: Klatovska nemocnice
city: Melnik
country: Czechia
facility: Fresenius Medical Care - DS, s.r.o.
city: Mlada Boleslav
country: Czechia
facility: Oblastni nemocnice Mlada Boleslav
city: Duesseldorf
country: Germany
facility: DaVita Clinical Research Deutschland GmbH
state: Nordrhein-Westfalen
city: Geilenkirchen
country: Germany
facility: DaVita Clinical Resarch Germany GmbH
state: Nordrhein-Westfalen
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein (UKSH)
state: Schleswig-Holstein
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Patra
country: Greece
facility: University General Hospital of Patra
city: Pilea Chortiatis
country: Greece
facility: PAPANIKOLAOU General Hospital Thessaloniki
city: Kalocsa
country: Hungary
facility: Bacs-Kiskun Megyei Korhaz
city: Szeged
country: Hungary
facility: SZTE ÁOK Szent Györgyi Albert Klinikai Kozpont
city: Hashima-gun
country: Japan
facility: Matsunami General Hospital
state: Gifu
city: Sapporo
country: Japan
facility: Sapporo Tokushukai Hospital
state: Hokkaido
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital
state: Ibaraki
city: Hakusan
country: Japan
facility: Public Central Hospital of Matto Ishikawa
state: Ishikawa
city: Fujisawa
country: Japan
facility: Shonan Fujisawa Tokushukai Hospital
state: Kanagawa
city: Hanyu
country: Japan
facility: Hanyu General Hospital
state: Saitama
city: Chiba
country: Japan
facility: Medical corporation association Shunshin-kai Inage hospital
city: Incheon
country: Korea, Republic of
facility: The Catholic University of Korea, Incheon St.Mary's Hospital
state: Incheon Gwang''yeogsi
city: Seoul
country: Korea, Republic of
facility: Yeouido St. Mary's Hospital
state: Seoul Teugbyeolsi
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Liepaja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital
city: Valmiera
country: Latvia
facility: Vidzemes Hospital
city: Moscow
country: Russian Federation
facility: High Technology Center Clinic 1
city: Novosibirsk
country: Russian Federation
facility: Limited Liability Company "Nefroline-Novosibirsk"
city: Penza
country: Russian Federation
facility: LLC Frezenius Nefrocare
city: Podolsk
country: Russian Federation
facility: LLC Dialysis center
city: Saint-Petersburg
country: Russian Federation
facility: Nikiforov All-Russian Center of Emergency and Radiation Med
city: St. Petersburg
country: Russian Federation
facility: Botkin clinical infectious diseases hospital
city: St. Petersburg
country: Russian Federation
facility: LLC B. Brown Avitum Russland Clinics
city: St. Petersburg
country: Russian Federation
facility: State Budgetary Healthcare Institution City Hospital #26
city: Alcalá de Henares
country: Spain
facility: Hospital Principe de Asturias
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge | Bellvitge Biomedical Research Institute - Cardiology - AF, Stroke Prevention
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves|Nefrologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politècnic La Fe | Nefrología
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Chernigiv
country: Ukraine
facility: Medical Center Fresenius Medical Care Ukraine, LLC
city: Kyiv
country: Ukraine
facility: Kyiv City Center of Nephrology and Dialysis
city: Kyiv
country: Ukraine
facility: Kyiv Regional Clinical Hospital
city: Odesa
country: Ukraine
facility: Regional Clinical Hospital - Odessa
city: Ternopil
country: Ukraine
facility: Ternopil Regional Clinical Hospital
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhia Municipal Clinical Hospital No.10
Study officials:
References: