Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis
- Conditions
- Atherosclerotic Cardiovascular DiseaseEnd Stage Kidney DiseaseAtherosclerotic Cardiovascular Disease in Patients With ESKD
- Interventions
- Drug: 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 cardiovascular (CV) outcomes and safety in subjects with systemic inflammation and either atherosclerotic cardiovascular disease (ASCVD) or diabetes with end stage kidney disease (ESKD) 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
- Clinically significant active infection or history of opportunistic or invasive fungal infection
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo (Phase 2b) Placebo IV administration Placebo (Phase 3) Placebo IV administration CSL300 (high dose)(Phase 2b) CSL300 IV administration CSL300 (Phase 3) CSL300 IV administration CSL300 (low dose)(Phase 2b) CSL300 Intravenous (IV) administration CSL300 (medium dose)(Phase 2b) CSL300 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) Baseline and up to 12 weeks Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3) Approximately 5 years
- Secondary Outcome Measures
Name Time Method Percent of participants achieving hs-CRP less than (<) 2.0 milligram per Liter (mg/L) (Phase 2b) Week 12 Change from baseline in log-transformed hs-CRP (Phase 2b) Baseline and up to 24 weeks Mean change from Baseline in serum amyloid A (SAA) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in secretory phospholipase A2 (sPLA2) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in fibrinogen (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in plasminogen activator inhibitor -1 (PAI-1) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in lipoprotein (Lp) (a) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in albumin (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in Hepcidin (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in hemoglobin (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in erythropoietin-resistance index (ERI) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in iron (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in total iron binding capacity (TIBC) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in transferrin saturation (TSAT) (Phase 2b) Baseline and up to 12 weeks Mean change from Baseline in ferritin (Phase 2b) Baseline and up to 12 weeks Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b) Up to 24 weeks Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b) Up to 24 weeks Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b) Up to 24 weeks Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b) Up to 24 weeks Percent of participants with adverse events (AE), serious AE (SAE), including adverse events of special interest (AESIs) (Phase 2b) Up to 32 weeks Mean change from Baseline in white blood cell (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 aspartate aminotransferase (AST) (Phase 2b) Up to 12 weeks Mean change from Baseline in alanine aminotransferase (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 total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (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 (HF) (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 Mean change from Baseline in erythropoiesis-stimulating agents (ESA) (Phase 2b) Baseline and up to 12 weeks
Trial Locations
- Locations (355)
84000622 - Southern Arizona VA Health Care System
🇺🇸Tucson, Arizona, United States
84000880 - Laguna Clinical Research Associates, LLC
🇺🇸Laredo, Texas, United States
03600060 - Austin Hospital
🇦🇺Heidelberg, Australia
03600041 - Royal Melbourne Hospital
🇦🇺Parkville, Australia
03600058 - Sydney Adventist Hospital
🇦🇺Wahroonga, Australia
04000006 - Wiener Gesundheitsverbund - Klinik Hietzing
🇦🇹Vienna, Austria
10000004 - Multiprofile Hospital For Active Treatment Dr Tota Venkova
🇧🇬Gabrovo, Bulgaria
10000011 - Multiprofile Hospital for Active Treatment Dr. Ivan Seliminski - Sliven AD
🇧🇬Sliven, Bulgaria
15600053 - People's Hospital of Deyang
🇨🇳Deyang Shi, China
25000032 - Fondation Charles Mion AIDER Santé
🇫🇷Grabels, France
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