Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis
- Conditions
- Atherosclerotic Cardiovascular DiseaseEnd Stage Kidney Disease
- Interventions
- Drug: CSL300Drug: Placebo
- Registration Number
- NCT05485961
- Lead Sponsor
- CSL Behring
- Brief Summary
This is a 2-part (phase 2b/3) prospective, interventional, multicenter, randomized, double blind, placebo controlled study. Part 1 (phase 2b) is a dose-finding study for CSL300 vs placebo. Part 2 (phase 3) aims to assess the efficacy of CSL300 on CV outcomes and safety in subjects with ASCVD or diabetes mellitus and evidence of systemic inflammation who are undergoing maintenance dialysis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 2310
- Male or female at least 18 years of age
- A diagnosis of ESKD undergoing maintenance dialysis for at least 12 weeks
- Serum hs-CRP ≥ 2.0 mg/L
- A diagnosis of diabetes mellitus OR ASCVD
- Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3)
- Concomitant use of systemic immunosuppressant drugs
- Abnormal LFTs
- Any life-threatening disease expected to result in death within 12 months
- A history of GI perforation, inflammatory bowel disease (except fully excised ulcerative colitis), or peptic ulcer disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CSL300 (low dose)(Phase 2b) CSL300 Intravenous (IV) administration CSL300 (medium dose)(Phase 2b) CSL300 IV administration CSL300 (high dose)(Phase 2b) CSL300 IV administration Placebo (Phase 2b) Placebo IV administration CSL300 (Phase 3) CSL300 IV administration Placebo (Phase 3) Placebo IV administration
- Primary Outcome Measures
Name Time Method Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b) Up to 12 weeks Time to first occurrence of CV death or MI (Phase 3) Approximately 5 years
- Secondary Outcome Measures
Name Time Method Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b) Up to 24 weeks Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b) Up to 24 weeks Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b) Up to 24 weeks Percent of subjects achieving hs-CRP < 2.0 mg/L (Phase 2b) Week 12 Change from baseline in log-transformed hs-CRP (Phase 2b) Up to 24 weeks Mean change from Baseline in SAA (Phase 2b) Up to 12 weeks Mean change from Baseline in sPLA2 (Phase 2b) Up to 12 weeks Mean change from Baseline in fibrinogen (Phase 2b) Up to 12 weeks Mean change from Baseline in PAI-1 (Phase 2b) Up to 12 weeks Mean change from Baseline in Lp (a) (Phase 2b) Up to 12 weeks Mean change from Baseline in Hepcidin (Phase 2b) Up to 12 weeks Mean change from Baseline in hemoglobin (Phase 2b) Up to 12 weeks Mean change from Baseline in ESA (Phase 2b) Up to 12 weeks Mean change from Baseline in ERI (Phase 2b) Up to 12 weeks Mean change from Baseline in iron (Phase 2b) Up to 12 weeks Mean change from Baseline in TIBC (Phase 2b) Up to 12 weeks Mean change from Baseline in TSAT (Phase 2b) Up to 12 weeks Mean change from Baseline in ferritin (Phase 2b) Up to 12 weeks Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b) Up to 24 weeks Percent of subjects with AE, SAE, including AESIs (Phase 2b) Up to 32 weeks Mean change from Baseline in WBC (Phase 2b) Up to 12 weeks Mean change from Baseline in neutrophils (Phase 2b) Up to 12 weeks Mean change from Baseline in platelets (Phase 2b) Up to 12 weeks Mean change from Baseline in AST (Phase 2b) Up to 12 weeks Mean change from Baseline in ALT (Phase 2b) Up to 12 weeks Mean change from Baseline in total bilirubin (Phase 2b) Up to 12 weeks Mean change from Baseline in lipid panel (Phase 2b) Up to 12 weeks Lipid panel consists of TC, LDL-C, HDL-C, triglyceride
Titer of confirmed antibodies specific to CSL300 (Phase 2b) Up to 12 weeks Time to first occurrence of all-cause death or MI (Phase 3) Approximately 5 years Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3) Approximately 5 years Time to first occurrence of CV death (Phase 3) Approximately 5 years Time to first occurrence of CV death, MI or major adverse limb event (Phase 3) Approximately 5 years Time to first occurrence of all-cause death (Phase 3) Approximately 5 years Time to first occurrence of CV death, MI, or hospitalization for heart failure (Phase 3) Approximately 5 years Total number of CV hospitalizations (Phase 3) Approximately 5 years Total number of HF hospitalizations and urgent visits (Phase 3) Approximately 5 years Total number of hospitalizations (Phase 3) Approximately 5 years
Trial Locations
- Locations (182)
84000228 - National Nephrology Alliance Research - Riverside
🇺🇸Riverside, California, United States
84000453 - Nephrology Physician's LLC
🇺🇸Mishawaka, Indiana, United States
84000436 - Hypertension & Nephrology Association
🇺🇸Eatontown, New Jersey, United States
84000196 - Southwest Houston Research
🇺🇸Houston, Texas, United States
03600023 - Royal North Shore Hospital (RNSH)
🇦🇺Saint Leonards, New South Wales, Australia
03600048 - Wollongong Renal Unit
🇦🇺Wollongong, Australia
20800010 - Herlev Hospital
🇩🇰Herlev, Denmark
27600039 - Westpfalz Klinikum GmbH
🇩🇪Kaiserslautern, Germany
30000002 - General Hospital of Ioannina G. Hatzikosta
🇬🇷Ioánnina, Greece
30000008 - University Hospital of Patras
🇬🇷Rio, Greece
30000006 - General Hospital of Thessaloniki, Agios Pavlos
🇬🇷Thessaloníki, Greece
30000016 - General Hospital of Arta
🇬🇷Árta, Greece
37600011 - Chaim Sheba Medical Center (Sheba Tel-Hashomer Medical Center )
🇮🇱Ramat Gan, Israel
38000074 - Ospedale Santa Maria Annunziata
🇮🇹Florence, Italy
38000019 - ICS Maugeri S.p.A. SB; Università di Pavia; Fondazione Salvatore Maugeri IRCCS
🇮🇹Pavia, Italy
38000067 - Rimini Hospital
🇮🇹Rimini, Italy
39200046 - Steel Memorial Yawata Hospital
🇯🇵Kitakyushu-shi, Fukuoka, Japan
39200027 - Tokyo Womens Med University
🇯🇵Shinjuku-Ku, Tokyo, Japan
39200021 - Kurume University Hospital
🇯🇵Kurume, Japan
39200051 - Bosei Kannai Clinic
🇯🇵Yokohama-shi, Japan
64200016 - Spitalul Clinic Judetean de Urgenta Sf. Apostol Andrei Constanta (Emergency Clinic Hospital Constanta)
🇷🇴Constanta, Romania
82600027 - Bradford Teaching Hospitals NHS Foundation Trust
🇬🇧Bradford, United Kingdom
84000149 - Nephrology Consultants, LLC
🇺🇸Huntsville, Alabama, United States
84000340 - DaVita Clinical Research Montgomery
🇺🇸Montgomery, Alabama, United States
84000552 - AKDHC Medical
🇺🇸Glendale, Arizona, United States
84000178 - Kidney Disease Medical Group
🇺🇸Glendale, Arizona, United States
84000231 - AKDHC Medical
🇺🇸Phoenix, Arizona, United States
84000286 - AKDHC Medical
🇺🇸Tucson, Arizona, United States
84000145 - National Institute of Clinical Research
🇺🇸Bakersfield, California, United States
84000151 - National Institute of Clinical Research
🇺🇸Bakersfield, California, United States
84000277 - Amicis Research Center
🇺🇸Beverly Hills, California, United States
84000241 - California Institute of Renal Research
🇺🇸Chula Vista, California, United States
84000462 - Davita Fullerton Dialysis Center
🇺🇸Fullerton, California, United States
84000574 - National Institute of Clinical Research, Inc.
🇺🇸Fullerton, California, United States
84000464 - St. Jude Medical Center
🇺🇸Garden Grove, California, United States
84000573 - National Institute of Clinical Research, Inc.
🇺🇸Garden Grove, California, United States
84000152 - National Institute of Clinical Research
🇺🇸Garden Grove, California, United States
84000531 - Sherman Medical Group, Inc
🇺🇸Glendale, California, United States
84000230 - Kidney Disease Medical Group
🇺🇸Glendale, California, United States
84000379 - Renal Consultants Medical Group
🇺🇸Granada Hills, California, United States
84000221 - California Institute of Renal Research
🇺🇸La Mesa, California, United States
84000235 - California Institute of Renal Research
🇺🇸La Mesa, California, United States
84000198 - Southern California Medical Research Center
🇺🇸La Palma, California, United States
84000467 - Southern California Medical Research Center
🇺🇸La Palma, California, United States
84000329 - Academic Medical Research Institute
🇺🇸Los Angeles, California, United States
84000439 - National Institute of Clinical Research, Inc.
🇺🇸Los Angeles, California, United States
84000158 - DaVita Carabello Dialysis Center
🇺🇸Los Angeles, California, United States
84000175 - Renal Medical Associates/NARI
🇺🇸Lynwood, California, United States
84000279 - Amicis Research Center
🇺🇸Northridge, California, United States
84000533 - FORMAT Medical Research
🇺🇸Oxnard, California, United States
84000331 - Van Buren Dialysis Center
🇺🇸Riverside, California, United States
84000238 - California Institute of Renal Research
🇺🇸San Diego, California, United States
84000143 - California Institute of Renal Research
🇺🇸San Diego, California, United States
84000330 - North America Research Institute
🇺🇸San Dimas, California, United States
84000341 - North America Research Institute
🇺🇸San Dimas, California, United States
84000281 - Satellite Healthcare
🇺🇸San Jose, California, United States
84000440 - Nephrology Educational Services
🇺🇸Tarzana, California, United States
84000278 - Amicis Research Center
🇺🇸Vacaville, California, United States
84000323 - National Institute of Clinical Research, Inc
🇺🇸Victorville, California, United States
84000174 - DaVita Vista Del Sol Dialysis
🇺🇸Victorville, California, United States
84000454 - Kidney Associates of Colorado, P.C.
🇺🇸Denver, Colorado, United States
84000223 - Colorado Kidney Care
🇺🇸Denver, Colorado, United States
84000176 - Greater Hartford Nephrology, LLC
🇺🇸Bloomfield, Connecticut, United States
84000173 - Nephrology and Hypertension Associates PC
🇺🇸Middlebury, Connecticut, United States
84000494 - Nephrology Associates (Delaware)
🇺🇸Newark, Delaware, United States
84000441 - Boca Raton Regional - Research Physicians Network Alliance
🇺🇸Boca Raton, Florida, United States
84000193 - Horizon Research Group LLC
🇺🇸Coral Gables, Florida, United States
84000443 - South Florida Nephrology Group, PA
🇺🇸Coral Springs, Florida, United States
84000406 - Elixia Pines
🇺🇸Hollywood, Florida, United States
84000140 -South Florida Research Institute
🇺🇸Lauderdale Lakes, Florida, United States
84000527 - Floridian Clinical Research
🇺🇸Miami Lakes, Florida, United States
84000495 - Total Research Group, LLC
🇺🇸Miami, Florida, United States
84000362 - Kidney and Hypertension Specialists of Miami
🇺🇸Miami, Florida, United States
84000182 - Nephrology Associates of South Miami
🇺🇸Miami, Florida, United States
84000400 - Elixia Central Florida
🇺🇸Orlando, Florida, United States
84000139 - Genesis Clinical Research
🇺🇸Tampa, Florida, United States
84000532 - Florida Kidney Specialists
🇺🇸Temple Terrace, Florida, United States
84000426 - Florida Premier Research Institute
🇺🇸Winter Park, Florida, United States
84000326 - Coastal Medical Research, LLC
🇺🇸Brunswick, Georgia, United States
84000157 - Renal Associates LLC
🇺🇸Columbus, Georgia, United States
84000327 - American Clinical Trials
🇺🇸Douglasville, Georgia, United States
84000194 - Atekha Nephrology Clinic LLC
🇺🇸Statesboro, Georgia, United States
84000534 - Dunes Clinical Research LLC
🇺🇸Sioux City, Iowa, United States
84000374 - Kansas Nephrology Physicians, PA
🇺🇸Wichita, Kansas, United States
84000554 - Nephrology Associates of Kentuckiana, PSC
🇺🇸Louisville, Kentucky, United States
84000550 - Renal Associates of Baton Rouge
🇺🇸Baton Rouge, Louisiana, United States
84000465 - Paragon Health, Inc
🇺🇸Kalamazoo, Michigan, United States
84000408 - Michigan Kidney Consultants, PC
🇺🇸Pontiac, Michigan, United States
84000171 - St. Clair Nephrology Research
🇺🇸Roseville, Michigan, United States
84000237 - Center for Advanced Kidney Research, PLC
🇺🇸Saint Clair Shores, Michigan, United States
84000146 - DCR Edina
🇺🇸Minneapolis, Minnesota, United States
84000338 - DCR Edina
🇺🇸Minneapolis, Minnesota, United States
84000225 - Southwest Mississippi Nephrology PLLC
🇺🇸Brookhaven, Mississippi, United States
84000153 - Nephrology Associates, PC
🇺🇸Columbus, Mississippi, United States
84000144 - Nephrology and Hypertension Associates Ltd
🇺🇸Tupelo, Mississippi, United States
84000147 - Clinical Research Consultants
🇺🇸Kansas City, Missouri, United States
84000328 - GSR Enterprises, Inc.
🇺🇸Lincoln, Nebraska, United States
84000222 - Great Plains Health - Nephrology
🇺🇸North Platte, Nebraska, United States
84000420 - DaVita Clinical Research - Henderson
🇺🇸Henderson, Nevada, United States
84000337 - Kidney Specialists of Southern Nevada
🇺🇸Las Vegas, Nevada, United States
84000148 - Sierra Nevada Specialty Care
🇺🇸Reno, Nevada, United States
84000141 - Seacoast Kidney and Hypertension Specialists
🇺🇸Portsmouth, New Hampshire, United States
84000452 - New Jersey Kidney Care
🇺🇸Jersey City, New Jersey, United States
84000155 - DaVita Clinic Research Bronx
🇺🇸Bronx, New York, United States
84000276 - Albert Einstein College of Medicine - Montefiore Medical Center
🇺🇸Bronx, New York, United States
84000184 - Mattoo & Bhat Medical Associates, P.C.
🇺🇸College Point, New York, United States
84000191 - Metrolina Nephrology Associates, PA
🇺🇸Charlotte, North Carolina, United States
84000150 - Durham Nephrology Associates, PA
🇺🇸Durham, North Carolina, United States
84000232 - East Carolina University
🇺🇸Greenville, North Carolina, United States
84000410 - North Carolina Nephrology, PA
🇺🇸Raleigh, North Carolina, United States
84000548 - HNC Dialysis, Ltd.
🇺🇸Columbus, Ohio, United States
84000234 - Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
84000192 - Columbia Nephrology
🇺🇸Columbia, South Carolina, United States
84000229 - DaVita Clinical Research
🇺🇸Spartanburg, South Carolina, United States
84000180 - Knoxville Kidney Center PLLC
🇺🇸Knoxville, Tennessee, United States
84000451 - Cussimanio Research Group LLC
🇺🇸Austin, Texas, United States
84000438 - Research Management, Inc.
🇺🇸Austin, Texas, United States
84000457 - US Renal Care
🇺🇸Dallas, Texas, United States
84000354 - Davita Clinical Research
🇺🇸El Paso, Texas, United States
84000421 - DaVita Clinical Research - Horizon
🇺🇸El Paso, Texas, United States
84000458 - Fort Worth Renal Group
🇺🇸Fort Worth, Texas, United States
84000350 - DaVita Clinical Research
🇺🇸Houston, Texas, United States
84000498 - DaVita Clinical Research
🇺🇸Houston, Texas, United States
84000450 - Houston Medical Research Institute, LLC
🇺🇸Houston, Texas, United States
84000360 - Clinical Research Strategies, Inc.
🇺🇸Houston, Texas, United States
84000373 - Gamma Medical Research, Inc.
🇺🇸McAllen, Texas, United States
84000324 - National Institute of Clinical Research, Inc.
🇺🇸San Antonio, Texas, United States
84000351 - DaVita Clinical Research
🇺🇸San Antonio, Texas, United States
84000419 - Davita Clinical Research
🇺🇸San Antonio, Texas, United States
84000553 - DCR-San Antonio Stone Oak
🇺🇸San Antonio, Texas, United States
84000339 - DaVita Clinical Research North Houston
🇺🇸Shenandoah, Texas, United States
84000535 - DCR-Norfolk Great Bridge
🇺🇸Chesapeake, Virginia, United States
84000424 - Nephrology Associates of Northern Virginia Inc
🇺🇸Fairfax, Virginia, United States
84000138 - Peninsula Kidney Associates
🇺🇸Hampton, Virginia, United States
84000156 - Tidewater Kidney Specialists
🇺🇸Norfolk, Virginia, United States
84000336 - Nephrology and Hypertension Associates
🇺🇸Bluefield, West Virginia, United States
03600017 - Concord Repatriation General Hospital
🇦🇺Sydney, New South Wales, Australia
03600021 - Sunshine Coast University Private Hospital
🇦🇺Nambour, Queensland, Australia
03600014 - Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
03600013 - Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
03600011 - Sunshine Hospital
🇦🇺St Albans, Victoria, Australia
05600011 - Onze-Lieve-Vrouwziekenhuis VZW
🇧🇪Aalst, Belgium
05600005 - Imelda Ziekenhuis
🇧🇪Bonheiden, Belgium
05600004 - AZ Sint-Lucas
🇧🇪Gent, Belgium
05600012 - Universitair Ziekenhuis Leuven
🇧🇪Leuven, Belgium
05600003 - CHR de la Citadelle
🇧🇪Liège, Belgium
12400008 - University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
12400021 - Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
12400009 - Kingston Health Sciences Centre
🇨🇦Kingston, Ontario, Canada
27600022 - UKSH - Universitatsklinik Schleswig-Holstein
🇩🇪Kiel, Germany
27600020 - Nephrologisches Zentrum Villingen-Schwenningen
🇩🇪Villingen-Schwenningen, Germany
30000004 - University General Hospital of Ioannina
🇬🇷Ioánnina, Greece
30000005 - Aristotle University, Hippokration
🇬🇷Thessaloniki, Greece
30000009 - Papageorgiou General Hospital of Thessaloniki
🇬🇷Thessaloníki, Greece
30000011 - Nephrology Department G. Papanikolaou General Hospital
🇬🇷Thessaloníki, Greece
38000031 - Azienda Ospedaliera Sant'Anna e San Sebastiano di Caserta
🇮🇹Caserta, Italy
38000027 - A. O. -Universitaria Ospedali Riuniti di Foggia Farmacia Osp
🇮🇹Foggia, Italy
39200053 - Daiyukai Daiichi Hospital
🇯🇵Ichinomiya-shi, Aichi, Japan
39200044 - Juntendo University Urayasu Hospital
🇯🇵Urayasu-shi, Chiba-ken, Japan
39200048 - Maebashi Hirosegawa Clinic
🇯🇵Maebashi-shi, Gunma, Japan
39200049 - Joumou Ohashi Clinic
🇯🇵Maebashi-shi, Gunma, Japan
39200045 - Teine Urological Clinic
🇯🇵Sapporo-shi, Hokkaido, Japan
39200054 - Omi freai Hospital
🇯🇵Kusatsu-shi, Shiga, Japan
39200042 - Matsunami General Hospital
🇯🇵Hashima-gun, Japan
39200041 - Ishikiriseiki Hospital
🇯🇵Higashiosaka-shi, Japan
39200033 - Tokyo Medical University Ibaraki Medical Center
🇯🇵Inashiki-gun, Japan
39200043 - Ueyama Hospital
🇯🇵Kagoshima-shi, Japan
39200038 - St. Mary's Hospital
🇯🇵Kurume-shi, Japan
39200028 - Rakuwakai Otowa Kinen Hospital
🇯🇵Kyoto-Shi, Japan
39200037 - Nagaoka Red-Cross Hospital
🇯🇵Nagaoka-Shi, Japan
39200035 - Daido Hospital
🇯🇵Nagoya-shi, Japan
39200020 - Chubu Rosai Hospital
🇯🇵Nagoya, Japan
39200026 - Omihachiman Community Medical Center - Kidney Center
🇯🇵Omihachiman, Japan
39200032 - Oguranaika Jin Cinic
🇯🇵Oyama-shi, Japan
39200029 - Ibaraki Seinan Medical Center Hospital
🇯🇵Sakaimachi, Japan
39200031 - Kurosawa Hospital
🇯🇵Takasaki-Shi, Japan
39200034 - Kikuchi Medical Clinic
🇯🇵Tsukuba-shi, Japan
39200030 - St.Hill Hospital
🇯🇵Ube-shi, Japan
39200036 - Sanin Rosai Hospital
🇯🇵Yonago-shi, Japan
62000011 - Unidade Local de Saúde de Braga, E. P. E.
🇵🇹Braga, Portugal
62000009 - Unidade Local de Saúde de São José, E. P. E.
🇵🇹Oeiras, Portugal
75200001 - Uppsala Universitet - Akademiska Sjukhuset
🇸🇪Uppsala, Sweden