Study to Investigate the Safety of a Drug Called Osocimab at Low and High Doses in Adult Patients With Kidney Failure Requiring Regular Hemodialysis
- Conditions
- End-stage Renal DiseasePrevention of Thromboembolic EventsHemodiafiltrationHemodialysis
- Interventions
- Drug: PlaceboDrug: BAY1213790 (Osocimab)
- Registration Number
- NCT04523220
- Lead Sponsor
- Bayer
- Brief Summary
In this study researchers want to learn about the safety of drug Osocimab at lower-dose and higher-doses in adult participants with kidney disease undergoing regular dialysis (a procedure that uses a machine to get rid of toxins and extra fluids in the blood). Patients with kidney disease undergoing regular dialysis are at high risk for heart and blood vessels diseases. Osocimab is a human monoclonal antibody under development for the prevention of events caused by blood clots like heart attack, stroke and death due to heart or blood vessels diseases. It works by binding to and blocking the activated form of clotting factor XI which increases the formation and stability of clots. Researchers also want to find out how drug Osocimab works in human body and how the body absorbs, distributes and excretes the drug.
Participants in this study will receive monthly injection of either Osocimab at a lower-dose or higher-dose or placebo (a placebo looks like a treatment but does not have any medicine in it). Both Osocimab and placebo will be injected into the tissue under the skin of the belly. Observation for each participant will last up to 23 months. Blood samples will be collected from the participants to monitor the safety and measure the blood level of the study drug.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 704
- Participants must be at least 18 years of age
- Patients with end-stage renal disease on hemodialysis (including hemodiafiltration) for ≥3 months, receiving dialysis at least 9 hours a week and stable in the view of the investigator
- Body weight of at least 50 kg
- Male and/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.
- Recent (<6 months before screening) clinically significant bleeding
- Hemoglobin (Hb) < 9.0 g/dL at screening
- Platelet count < 100 x 10^9/L
- aPTT or PT > ULN (upper limit of normal)
- Hepatic disease associated with ALT > 3x ULN, or total bilirubin >2x ULN with direct bilirubin > 20% of the total
- Sustained uncontrolled hypertension (diastolic blood pressure ≥100 mmHg and/or systolic blood pressure ≥ 180 mmHg)
- Known intracranial neoplasm, arteriovenous malformation or aneurysm
- Known bleeding disorders e.g. von-Willebrand disease or Hemophilia A, B or C
- Recent (<3 months before screening) thromboembolic event, e.g. acute coronary syndrome, stroke or VTE (except dialysis access thrombosis)
- Recent (<3 months before screening) major surgery or scheduled major surgery during study participation
- Scheduled living donor renal transplant during study participation
- Persistent heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher
- Receiving antiplatelet therapy except daily ASA ≤ 150 mg/day
- Receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo high dose Placebo Placebo will be administered subcutaneously in the same manner as Osocimab. BAY1213790 high dose BAY1213790 (Osocimab) Participants will receive Osocimab (BAY1213790) 210 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 105 mg until the end of the extension treatment period. BAY1213790 low dose BAY1213790 (Osocimab) Participants will receive Osocimab (BAY1213790) 105 mg single loading dose as subcutaneous abdominal injection, followed by monthly maintenance doses of 52.5 mg until the end of the extension treatment period. Placebo low dose Placebo Placebo will be administered subcutaneously in the same manner as Osocimab.
- Primary Outcome Measures
Name Time Method Cumulative Incidence Risk of the First Composite of Major Bleeding (MB) and Clinically-relevant Non-major Bleeding (CRNMB) Events as Assessed by Blinded Central Independent Adjudication Committee (CIAC) From the first dose of study intervention up till 30 days after last study intervention in the main treatment period, up to 6 months Cumulative incidence risk of the first Composite of MB and CRNMB (ISTH) at month 6 is reported in the table.
Descriptive time to composite of MB and CRNMB Events is reported in statistical analysis.
Descriptive time to composite of treatment emergent major and CRNMB events \[in alignment with International Society on Thrombosis and Haemostatsis (ISTH) guidelines\] analyses were performed. The cumulative incidence function for the event-of-interest together with the corresponding confidence interval were estimated for each treatment arm using Aalen-Johansen estimators. Cumulative incidence of events up to the day, inclusive.Cumulative Incidence Risk of Composite of Moderate and Severe Adverse Events (AEs) and Serious Adverse Events (SAEs) From the first dose of study intervention up until 30 days after last study intervention in the main treatment period, up to 6 months Cumulative incidence risk of composite of moderate and severe AEs and SAEs at month 6 is reported in the table.
Descriptive time to the composite of Moderate and Severe AEs and SAEs is reported in statistical analysis.
An AE was any untoward medical occurrence in a patient or clinical study participant, whether or not considered related to the study intervention.
- Secondary Outcome Measures
Name Time Method Ratio of Activated Partial Thromboplastin Time (aPTT) at 6 Months Trough Levels Versus Baseline. At 6 months (Visit 19 / Day 30 of the 6th month) The aPTT at trough levels after 6 months were analyzed as ratio to baseline by providing the Geometric Mean (Standard Deviation).
aPTT was measured via the kaolin-trigger method (clotting assay).Ratio of Factor XI (FXI) Activity at 6 Months Trough Levels Versus Baseline At 6 months (Visit 19 / Day 30 of the 6th month) The Factor XI (FXI) activity at trough levels after 6 months were analyzed as ratio to baseline by providing the Geometric Mean (Standard Deviation).
Factor XI activity was assessed with an aPTT-based coagulation test using FXI deficient plasma.
Trial Locations
- Locations (148)
East L.A. Dialysis Center
🇺🇸Los Angeles, California, United States
Wojewodzki Szpital Zespolony
🇵🇱Kielce, Poland
HIPPOKRATION General Hospital of Athens
🇬🇷Athens, Greece
Albert Schweitzer Ziekenhuis, Dordwijk
🇳🇱Dordrecht, Netherlands
Fresenius Kidney Care South Dialysis
🇺🇸Shreveport, Louisiana, United States
Fresenius Kidney Care Baton Rouge Mancuso Lane
🇺🇸Baton Rouge, Louisiana, United States
DaVita Greater Waterbury Dialysis
🇺🇸Waterbury, Connecticut, United States
Klinikum Klagenfurt am Wörthersee
🇦🇹Klagenfurt, Kärnten, Austria
General Hospital of Arta
🇬🇷Arta, Greece
General Hospital of Athens LAIKO
🇬🇷Athens, Greece
General Hospital of Thessaloniki Papageorgiou
🇬🇷Thessaloniki, Greece
Bajai Szent Rokus Korhaz
🇭🇺Baja, Hungary
Yabuki Hospital
🇯🇵Yamagata, Japan
Stacja Dializ Zyrardow
🇵🇱Zyrardow, Poland
Eszak-Pesti Centrumkorhaz-Honvedkorhaz
🇭🇺Budapest, Hungary
Privatklinik Wehrle-Diakonissen
🇦🇹Salzburg, Austria
Imeldaziekenhuis - St-Elisabethkliniek
🇧🇪Bonheiden, Belgium
Ioannina University General Hospital
🇬🇷Ioannina, Greece
Fresenius Medical Care Egeszsegugyi Kft.
🇭🇺Pecs, Hungary
Lady Davis Carmel Medical Center
🇮🇱Haifa, Israel
Poriya Medical Center | Nephrology and Hypertension Dept.
🇮🇱Tiberius, Israel
Kikuchi Medical Clinic
🇯🇵Tsukuba, Ibaraki, Japan
Saiyu Clinic
🇯🇵Koshigaya, Saitama, Japan
Akebono Clinic
🇯🇵Kumamoto, Japan
Stacja Dializ Olkusz
🇵🇱Olkusz, Poland
IRCCS Ospedale Policlinico San Martino
🇮🇹Genova, Liguria, Italy
Klinik Landstraße - Krankenhaus Rudolfstiftung
🇦🇹Wien, Austria
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
UMHAT Kanev AD
🇧🇬Ruse, Bulgaria
Csongrad Megyei Egeszsegugyi Ellato Kozpont,Hodmezovasarhely
🇭🇺Hodmezovasarhely, Hungary
Barzilai Medical Center | Nephrology & Hypertension Dept.
🇮🇱Ashkelon, Israel
Clalit Health Services Rabin Medical Center-Beilinson Campus
🇮🇱Petah Tikva, Israel
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Lazio, Italy
Nagaoka Red Cross Hospital
🇯🇵Nagaoka, Niigata, Japan
Takemura Medical Nephro Clinic
🇯🇵Kanuma, Tochigi, Japan
Akagaki Clinic
🇯🇵Osaka, Japan
SPD - Amadora (Diaverum Amadora)
🇵🇹Amadora, Lisboa, Portugal
CHLO - Hospital Santa Cruz
🇵🇹Carnaxide, Lisboa, Portugal
Kupchinsky center for outpatient dialysis
🇷🇺St. Petersburg, Russian Federation
Medical center LLC " Fresenius medical care Ukraine"
🇺🇦Cherkasy, Ukraine
Futakotamagawaekimae clinic
🇯🇵Setagaya-ku, Tokyo, Japan
Caledial - Centro de Hemodialise de Gaia
🇵🇹Canelas, Porto, Portugal
Universitätsklinikum AKH Wien
🇦🇹Wien, Austria
Centro Hospitalar do Medio Tejo | Unidade de Torres Novas - Nephrology Department
🇵🇹Torres Novas, Santarém, Portugal
CHU de Liege | CHR Citadel - Department of Nephrology
🇧🇪Liege, Belgium
Multiprofile Hospital for Active Treatment Hristo Botev AD
🇧🇬Vratsa, Bulgaria
University General Hospital of Larissa
🇬🇷Larissa, Greece
Health Corporation of Galilee Medical Center
🇮🇱Nahariya, Israel
Rabin Medical Center, HaSharon (Golda) Campus
🇮🇱Petach Tikva, Israel
Ohishi Naika Clinic
🇯🇵Tsuchiura, Ibaraki, Japan
Gelre Ziekenhuizen
🇳🇱Apeldoorn, Netherlands
Catharina Ziekenhuis
🇳🇱Eindhoven, Netherlands
Eurodial Obidos (DaVita)
🇵🇹Gaeiras - Obidos, Leiria, Portugal
Diaverum Aveiro
🇵🇹Aveiro, Portugal
Keszthelyi Korhaz
🇭🇺Keszthely, Hungary
Tsuchiura Beryl Clinic
🇯🇵Tsuchiura, Ibaraki, Japan
NZOZ Nowy Szpital w Swieciu Sp. z o.o.
🇵🇱Swiecie, Poland
Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi
🇺🇦Poltava, Ukraine
Pluribus Dialise - Cascais (DaVita)
🇵🇹Cascais, Lisboa, Portugal
Eurodial Leiria (DaVita)
🇵🇹Leiria, Portugal
Pluribus Dialise - Sacavem (DaVita)
🇵🇹Sacavem, Lisboa, Portugal
Kyiv City Center of Nephrology and Dialysis
🇺🇦Kyiv, Ukraine
City Clinical Hospital #1 Orenburg
🇷🇺Orenburg, Russian Federation
Sverdlovsk Regional Clinical Hospital #1
🇷🇺Yekaterinburg, Russian Federation
Lutsk city clinical hospital
🇺🇦Lutsk, Ukraine
Vinnitsa Regional Clinical Hospital im. N.I. Pirogov
🇺🇦Vinnytsia, Ukraine
LLC Yaroslavl dialysis center
🇷🇺Yaroslavl, Russian Federation
Brovarskaya multidisciplinary clinical hospital
🇺🇦Brovary, Ukraine
Hospital Clínico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruña, Spain
Regional Clinical Hospital - Ivano-Frankivsk
🇺🇦Ivano-Frankivsk, Ukraine
State Institution "Institute of Nephrology" NAMS of Ukraine
🇺🇦Kyiv, Ukraine
Mykolaiv Regional Clinical Hospital
🇺🇦Mykolaiv, Ukraine
Kharkiv regional Clinical Centre of urology and nephrology
🇺🇦Kharkiv, Ukraine
Zaporizhzhia Regional Clinical Hospital
🇺🇦Zaporizhzhya, Ukraine
Transcarpatian Regional Clinical Hospital
🇺🇦Uzhgorod, Ukraine
North America Research Institute - Azusa
🇺🇸Azusa, California, United States
Fresenius Kidney Care - Brawley
🇺🇸Brawley, California, United States
DaVita South Valley Dialysis
🇺🇸Encino, California, United States
Fresenius Kidney Care - La Mesa
🇺🇸La Mesa, California, United States
Van Buren Dialysis Center
🇺🇸Riverside, California, United States
Fresenius Kidney Care Kearny Mesa
🇺🇸San Diego, California, United States
FMC San Ysidro
🇺🇸San Diego, California, United States
Queen's Dialysis Unit
🇺🇸West Covina, California, United States
Liberty Dialysis- Caldwell
🇺🇸Caldwell, Idaho, United States
Fresenius Kidney Care Evergreen Park
🇺🇸Evergreen Park, Illinois, United States
ARA Plantation Dialysis, LLC
🇺🇸Ellenton, Florida, United States
ARA Augusta
🇺🇸Augusta, Georgia, United States
Renal Medicine Associates
🇺🇸Albuquerque, New Mexico, United States
ARA Holyoke Dialysis Center
🇺🇸Holyoke, Massachusetts, United States
Durham Nephrology Associates, Pa
🇺🇸Durham, North Carolina, United States
Davita Hospital Hill Dialysis
🇺🇸Kansas City, Missouri, United States
Fresenius North Austin Dialysis Center
🇺🇸Austin, Texas, United States
Fresenius Kidney Care Sugar Land
🇺🇸Sugar Land, Texas, United States
Liberty Dialysis St. George
🇺🇸Saint George, Utah, United States
Fresenius Kidney Care - Mission Bend (FMCNA #3971)
🇺🇸Houston, Texas, United States
DaVita Butler Farm Dialysis
🇺🇸Hampton, Virginia, United States
Sydney Adventist Hospital
🇦🇺Wahroonga, New South Wales, Australia
John Hunter Hospital
🇦🇺New Lambton Heights, Australia
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Eastern Health Integrated Renal Service
🇦🇺Box Hill, Australia
Epicura
🇧🇪Baudour, Belgium
AZ St-Lucas Campus St-Lucas
🇧🇪Gent, Belgium
AZ Nikolaas Campus Sint-Niklaas
🇧🇪Sint-niklaas, Belgium
MHAT Haskovo
🇧🇬Haskovo, Bulgaria
MHAT Sveti Ivan Rilski 2003
🇧🇬Dupnitsa, Bulgaria
MHAT Shumen AD
🇧🇬Shumen, Bulgaria
Krajska Nemocnice Liberec
🇨🇿Liberec, Czechia
Privamed s.r.o.
🇨🇿Plzen, Czechia
Fresenius Nephro Care s.r.o. - Sokolov
🇨🇿Sokolov, Czechia
Fakultni nemocnice Ostrava
🇨🇿Ostrava, Czechia
Hippokration General Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
A.O.U. di Parma
🇮🇹Parma, Emilia-Romagna, Italy
Shamir Medical Center (Assaf Harofeh)
🇮🇱Zerifin, Israel
A.O.U. di Bologna Policlinico S.Orsola Malpighi
🇮🇹Bologna, Emilia-Romagna, Italy
AUSL-IRCCS di Reggio Emilia
🇮🇹Reggio Emilia, Emilia-Romagna, Italy
Ibaraki Seinan Medical Center Hospital
🇯🇵Sashima-gun, Ibaraki, Japan
IRCCS Istituti Clinici Scientifici Maugeri SpA SB
🇮🇹Pavia, Lombardia, Italy
A.O.U. Careggi
🇮🇹Firenze, Toscana, Italy
Katta General Hospital
🇯🇵Shiraishi, Miyagi, Japan
Kyoto Station Takeda Dialysis Clinic
🇯🇵Kyoto, Japan
Saint Hill Hospital
🇯🇵Ube, Yamaguchi, Japan
LUHS Kauno Hospital (Josvainiu str.)
🇱🇹Kaunas, Lithuania
Academisch Medisch Centrum (AMC)
🇳🇱Amsterdam, Netherlands
Deventer Ziekenhuis
🇳🇱Deventer, Netherlands
Maasstad Ziekenhuis | Neurology Department
🇳🇱Rotterdam, Netherlands
Stacja Dializ W-wa Mangalia
🇵🇱Warszawa, Poland
NephroCare APDP
🇵🇹Lisboa, Portugal
Chelyabinsk Regional Clinical Hospital
🇷🇺Chelyabinsk, Russian Federation
LLC Dialysis center
🇷🇺Mytishchi, Russian Federation
LLC Fresenius medical care Kuban
🇷🇺Krasnodar, Russian Federation
City Hospital #31
🇷🇺St. Petersburg, Russian Federation
Republican Hospital n.a. V.A. Baranov
🇷🇺Petrozavodsk, Russian Federation
LLC B. Brown Avitum Russland Clinics
🇷🇺St. Petersburg, Russian Federation
Hospital Clinico Universitario San Carlos | Nefrologia
🇪🇸Madrid, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Hospital Althaia, Xarxa Assistencial de Manresa
🇪🇸Manresa, Barcelona, Spain
Corporació Sanitària Parc Taulí
🇪🇸Sabadell, Barcelona, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Dr. Peset
🇪🇸Valencia, Spain
Hacettepe Universitesi Tip Fakultesi
🇹🇷Ankara, Turkey
Adnan Menderes Universitesi Tip fakultesi
🇹🇷Aydin, Turkey
Turk Bobrek Vakfi Memorial Hizmet Hastanesi
🇹🇷Istanbul, Turkey
Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi
🇹🇷Istanbul, Turkey
Kocaeli Universitesi Tip Fakultesi
🇹🇷Kocaeli, Turkey
Erciyes Universitesi Tip Fakultesi
🇹🇷Kayseri, Turkey
Inonu Universitesi Tip Fakultesi
🇹🇷Malatya, Turkey
Dnepropetrovsk regional hospital n.a. I. I. Mechnikov
🇺🇦Dnipro, Ukraine
Waterloo Dialysis
🇺🇸Austin, Texas, United States