Study to Investigate the Safety of a Drug Called Osocimab at Low and High Doses in Adult Patients With Kidney Failure Requiring Regular Hemodialysis (CONVERT)

A Randomized, Double-blind, Parallel Group, Placebo-controlled, Multi-center Study to Assess the Safety and Tolerability of Monthly Subcutaneous Administrations of a Low and High Dose Cohort of Osocimab to ESRD Patients on Regular Hemodialysis

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.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; End-stage Renal Disease; Hemodiafiltration; Prevention of Thromboembolic Events
• Intervention / Treatment: Drug: BAY1213790 (Osocimab); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 704
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Box Hill, Australia, 3128
    • Eastern Health Integrated Renal Service
  • New Lambton Heights, Australia, 2305
    • John Hunter Hospital
  • New South Wales
    • Wahroonga, New South Wales, Australia, 2076
      • Sydney Adventist Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
• Austria
  • Salzburg, Austria, 5026
    • Privatklinik Wehrle-Diakonissen
  • Wien, Austria, 1090
    • Universitätsklinikum AKH Wien
  • Wien, Austria, 1030
    • Klinik Landstraße - Krankenhaus Rudolfstiftung
  • Kärnten
    • Klagenfurt, Kärnten, Austria, 9020
      • Klinikum Klagenfurt am Wörthersee
• Belgium
  • Baudour, Belgium, 7331
    • EpiCURA
  • Bonheiden, Belgium, 2820
    • Imeldaziekenhuis - St-Elisabethkliniek
  • Gent, Belgium, 9000
    • AZ St-Lucas Campus St-Lucas
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liege, Belgium, 4000
    • CHU de Liege | CHR Citadel - Department of Nephrology
  • Sint-niklaas, Belgium, 9100
    • AZ Nikolaas Campus Sint-Niklaas
• Bulgaria
  • Dupnitsa, Bulgaria, 2600
    • MHAT Sveti Ivan Rilski 2003
  • Haskovo, Bulgaria, 6300
    • MHAT Haskovo
  • Ruse, Bulgaria, 7002
    • UMHAT Kanev AD
  • Shumen, Bulgaria, 9700
    • MHAT Shumen AD
  • Vratsa, Bulgaria, 3000
    • Multiprofile Hospital for Active Treatment Hristo Botev AD
• Czechia
  • Liberec, Czechia, 460 63
    • Krajska Nemocnice Liberec
  • Ostrava, Czechia, 708 52
    • Fakultni Nemocnice Ostrava
  • Plzen, Czechia, 323 33
    • Privamed s.r.o.
  • Sokolov, Czechia, 356 01
    • Fresenius Nephro Care s.r.o. - Sokolov
• Greece
  • Arta, Greece, 47100
    • General Hospital of Arta
  • Athens, Greece, 11527
    • General Hospital of Athens Laiko
  • Athens, Greece, 115 27
    • Hippokration General Hospital of Athens
  • Ioannina, Greece, 45500
    • Ioannina University General Hospital
  • Larissa, Greece, 41110
    • University General Hospital of Larissa
  • Thessaloniki, Greece, 54642
    • Hippokration General Hospital of Thessaloniki
  • Thessaloniki, Greece, 56403
    • General Hospital Of Thessaloniki Papageorgiou
• Hungary
  • Baja, Hungary, 6500
    • Bajai Szent Rokus Korhaz
  • Budapest, Hungary, 1083
    • Fresenius Medical Care Egeszsegugyi Kft.
  • Budapest, Hungary, 1134
    • Észak-Pesti Centrumkórház-Honvédkórház
  • Hodmezovasarhely, Hungary, 6800
    • Csongrad Megyei Egeszsegugyi Ellato Kozpont,Hodmezovasarhely
  • Keszthely, Hungary, 8360
    • Keszthelyi Korhaz
  • Miskolc, Hungary, 3526
    • Fresenius Medical Care Egeszsegugyi Kft.
  • Pecs, Hungary, 7624
    • Fresenius Medical Care Egeszsegugyi Kft.
• Israel
  • Ashkelon, Israel, 7830604
    • Barzilai Medical Center | Nephrology & Hypertension Dept.
  • Haifa, Israel, 3436212
    • Lady Davis Carmel Medical Center
  • Nahariya, Israel, 2210001
    • Health Corporation of Galilee Medical Center
  • Petach Tikva, Israel, 4937211
    • Rabin Medical Center, HaSharon (Golda) Campus
  • Petah Tikva, Israel, 4941492
    • Clalit Health Services Rabin Medical Center-Beilinson Campus
  • Tiberius, Israel, 1528001
    • Poriya Medical Center | Nephrology and Hypertension Dept.
  • Zerifin, Israel, 7030000
    • Shamir Medical Center (Assaf Harofeh)
• Italy
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O.U. di Bologna Policlinico S.Orsola Malpighi
    • Parma, Emilia-Romagna, Italy, 43126
      • A.O.U. di Parma
    • Reggio Emilia, Emilia-Romagna, Italy, 42123
      • AUSL-IRCCS di Reggio Emilia
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS Ospedale Policlinico San Martino
  • Lombardia
    • Pavia, Lombardia, Italy, 27100
      • IRCCS Istituti Clinici Scientifici Maugeri SpA SB
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • A.O.U. Careggi
• Japan
  • Kumamoto, Japan, 861-4112
    • Akebono Clinic
  • Kyoto, Japan, 600-8216
    • Kyoto Station Takeda Dialysis Clinic
  • Osaka, Japan, 543-0052
    • Akagaki Clinic
  • Yamagata, Japan, 990-0885
    • Yabuki Hospital
  • Ibaraki
    • Sashima-gun, Ibaraki, Japan, 306-0433
      • Ibaraki Seinan Medical Center Hospital
    • Tsuchiura, Ibaraki, Japan, 300-0835
      • Ohishi Naika Clinic
    • Tsuchiura, Ibaraki, Japan, 300-0062
      • Tsuchiura Beryl Clinic
    • Tsukuba, Ibaraki, Japan, 305-0861
      • Kikuchi Medical Clinic
  • Miyagi
    • Shiraishi, Miyagi, Japan, 989-0231
      • Katta General Hospital
  • Niigata
    • Nagaoka, Niigata, Japan, 940-2085
      • Nagaoka Red Cross Hospital
  • Saitama
    • Koshigaya, Saitama, Japan, 343-0823
      • Saiyu Clinic
  • Tochigi
    • Kanuma, Tochigi, Japan, 322-0029
      • Takemura Medical Nephro Clinic
  • Tokyo
    • Setagaya-ku, Tokyo, Japan, 158-0094
      • Futakotamagawaekimae clinic
  • Yamaguchi
    • Ube, Yamaguchi, Japan, 755-0155
      • Saint Hill Hospital
• Lithuania
  • Kaunas, Lithuania, LT-47116
    • LUHS Kauno Hospital (Josvainiu str.)
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum (AMC)
  • Apeldoorn, Netherlands, 7334 DZ
    • Gelre Ziekenhuizen
  • Deventer, Netherlands, 7416 SE
    • Deventer Ziekenhuis
  • Dordrecht, Netherlands, 3318 AT
    • Albert Schweitzer Ziekenhuis, Dordwijk
  • Eindhoven, Netherlands, 5623 EJ
    • Catharina Ziekenhuis
  • Rotterdam, Netherlands, 3079DZ
    • Maasstad Ziekenhuis | Neurology Department
• Poland
  • Kielce, Poland, 25-736
    • Wojewodzki Szpital Zespolony
  • Olkusz, Poland, 32-300
    • Stacja Dializ Olkusz
  • Swiecie, Poland, 86-100
    • NZOZ Nowy Szpital w Swieciu Sp. z o.o.
  • Warszawa, Poland, 02-758
    • Stacja Dializ W-wa Mangalia
  • Zyrardow, Poland, 96-300
    • Stacja Dializ Zyrardow
• Portugal
  • Aveiro, Portugal, 3800-266
    • Diaverum Aveiro
  • Leiria, Portugal, 2400-441
    • Eurodial Leiria (DaVita)
  • Lisboa, Portugal, 1250-191
    • NephroCare APDP
  • Leiria
    • Gaeiras - Obidos, Leiria, Portugal, 2510-702
      • Eurodial Obidos (DaVita)
  • Lisboa
    • Amadora, Lisboa, Portugal, 2700-001
      • SPD - Amadora (Diaverum Amadora)
    • Carnaxide, Lisboa, Portugal, 2795-53
      • CHLO - Hospital Santa Cruz
    • Cascais, Lisboa, Portugal, 2750-663
      • Pluribus Dialise - Cascais (DaVita)
    • Sacavem, Lisboa, Portugal, 2685-005
      • Pluribus Dialise - Sacavem (DaVita)
  • Porto
    • Canelas, Porto, Portugal, 4410-313
      • Caledial - Centro de Hemodiálise de Gaia
  • Santarém
    • Torres Novas, Santarém, Portugal, 2350-754
      • Centro Hospitalar do Medio Tejo | Unidade de Torres Novas - Nephrology Department
• Russian Federation
  • Chelyabinsk, Russian Federation, 454076
    • Chelyabinsk Regional Clinical Hospital
  • Kolomna, Russian Federation, 140402
    • LLC Dialysis center
  • Krasnodar, Russian Federation, 350029
    • LLC Fresenius medical care Kuban
  • Mytishchi, Russian Federation, 141007
    • LLC Dialysis center
  • Orenburg, Russian Federation, 460040
    • City Clinical Hospital #1 Orenburg
  • Petrozavodsk, Russian Federation, 185019
    • Republican Hospital n.a. V.A. Baranov
  • St. Petersburg, Russian Federation, 192102
    • Kupchinsky center for outpatient dialysis
  • St. Petersburg, Russian Federation, 193318
    • LLC B. Brown Avitum Russland Clinics
  • St. Petersburg, Russian Federation, 197110
    • City Hospital #31
  • Yaroslavl, Russian Federation, 150062
    • LLC Yaroslavl dialysis center
  • Yekaterinburg, Russian Federation, 620102
    • Sverdlovsk Regional Clinical Hospital #1
• Spain
  • Madrid, Spain, 28040
    • Hospital Clinico Universitario San Carlos | Nefrologia
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clinico Universitario de Santiago de Compostela
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Manresa, Barcelona, Spain, 08243
      • Hospital Althaia, Xarxa Assistencial de Manresa
    • Sabadell, Barcelona, Spain, 08208
      • Corporacio Sanitaria Parc Tauli
• Turkey
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi Tip Fakultesi
  • Aydin, Turkey, 09100
    • Adnan Menderes Universitesi Tip fakultesi
  • Istanbul, Turkey, 34180
    • Turk Bobrek Vakfi Memorial Hizmet Hastanesi
  • Istanbul, Turkey, 34418
    • Sisli Hamidiye Etfal Egitim ve Arastirma Hastanesi
  • Kayseri, Turkey, 38039
    • Erciyes Universitesi Tip Fakultesi
  • Kocaeli, Turkey, 41380
    • Kocaeli Universitesi Tip Fakultesi
  • Malatya, Turkey, 44280
    • Inonu Universitesi Tip Fakultesi
• Ukraine
  • Brovary, Ukraine, 07400
    • Brovarskaya multidisciplinary clinical hospital
  • Cherkasy, Ukraine, 18009
    • Medical center LLC " Fresenius medical care Ukraine"
  • Dnipro, Ukraine, 49005
    • Dnepropetrovsk regional hospital n.a. I. I. Mechnikov
  • Ivano-Frankivsk, Ukraine, 76000
    • Regional Clinical Hospital - Ivano-Frankivsk
  • Kharkiv, Ukraine, 61037
    • Kharkiv regional Clinical Centre of urology and nephrology
  • Kyiv, Ukraine, 02660
    • Kyiv City Center of Nephrology and Dialysis
  • Kyiv, Ukraine, 04050
    • State Institution "Institute of Nephrology" NAMS of Ukraine
  • Lutsk, Ukraine, 43024
    • Lutsk City Clinical Hospital
  • Mykolaiv, Ukraine, 54058
    • Mykolaiv Regional Clinical Hospital
  • Poltava, Ukraine, 36011
    • Poltava Regional Clinical Hospital n.a. M.V. Skliphosovskyi
  • Uzhgorod, Ukraine, 88018
    • Transcarpatian Regional Clinical Hospital
  • Vinnytsia, Ukraine, 21018
    • Vinnitsa Regional Clinical Hospital im. N.I. Pirogov
  • Zaporizhzhya, Ukraine, 69600
    • Zaporizhzhia Regional Clinical Hospital
• United States
  • California
    • Azusa, California, United States, 91702
      • North America Research Institute - Azusa
    • Brawley, California, United States, 92227
      • Fresenius Kidney Care - Brawley
    • Encino, California, United States, 91316
      • DaVita South Valley Dialysis
    • La Mesa, California, United States, 91942
      • Fresenius Kidney Care - La Mesa
    • Los Angeles, California, United States, 90022
      • East L.A. Dialysis Center
    • Riverside, California, United States, 92503
      • Van Buren Dialysis Center
    • San Diego, California, United States, 92111
      • Fresenius Kidney Care Kearny Mesa
    • San Diego, California, United States, 92154
      • FMC San Ysidro
    • West Covina, California, United States, 91790
      • Queen's Dialysis Unit
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • DaVita Greater Waterbury Dialysis
  • Florida
    • Ellenton, Florida, United States, 34222
      • ARA Plantation Dialysis, LLC
  • Georgia
    • Augusta, Georgia, United States, 30901
      • ARA Augusta
  • Idaho
    • Caldwell, Idaho, United States, 83605
      • Liberty Dialysis- Caldwell
  • Illinois
    • Evergreen Park, Illinois, United States, 60805
      • Fresenius Kidney Care Evergreen Park
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Fresenius Kidney Care Baton Rouge Mancuso Lane
    • Shreveport, Louisiana, United States, 71106
      • Fresenius Kidney Care South Dialysis
  • Massachusetts
    • Holyoke, Massachusetts, United States, 01040
      • ARA Holyoke Dialysis Center
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Davita Hospital Hill Dialysis
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Renal Medicine Associates
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Durham Nephrology Associates, PA
  • Texas
    • Austin, Texas, United States, 78756
      • Waterloo Dialysis
    • Austin, Texas, United States, 78758
      • Fresenius North Austin Dialysis Center
    • Houston, Texas, United States, 77083
      • Fresenius Kidney Care - Mission Bend (FMCNA #3971)
    • Sugar Land, Texas, United States, 77479
      • Fresenius Kidney Care Sugar Land
  • Utah
    • Saint George, Utah, United States, 84790
      • Liberty Dialysis St. George
  • Virginia
    • Hampton, Virginia, United States, 23666
      • DaVita Butler Farm Dialysis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY1213790 low dose; 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.	Drug: BAY1213790 (Osocimab); Single loading dose as subcutaneous abdominal injection followed by monthly maintenance doses.
Placebo Comparator: Placebo low dose; Placebo will be administered subcutaneously in the same manner as Osocimab.	Drug: Placebo; Subcutaneous administration in the same manner as Osocimab.
Experimental: BAY1213790 high dose; 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.	Drug: BAY1213790 (Osocimab); Single loading dose as subcutaneous abdominal injection followed by monthly maintenance doses.
Experimental: Placebo high dose; Placebo will be administered subcutaneously in the same manner as Osocimab.	Drug: Placebo; Subcutaneous administration in the same manner as Osocimab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	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 Composite of Moderate and Severe Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	From the first dose of study intervention up until 30 days after last study intervention in the main treatment period, up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of Activated Partial Thromboplastin Time (aPTT) at 6 Months Trough Levels Versus Baseline.	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).	At 6 months (Visit 19 / Day 30 of the 6th month)
Ratio of Factor XI (FXI) Activity at 6 Months Trough Levels Versus Baseline	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.	At 6 months (Visit 19 / Day 30 of the 6th month)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful 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 Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Actual): December 28, 2021
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): July 21, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Hemodialysis; End-stage renal disease (ESRD)
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Embolism and Thrombosis; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Kidney Failure, Chronic; Thromboembolism
• Other Study ID Numbers: 20115; 2019-003957-27 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There are no current plans to share data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No