End Stage Kidney Disease
Conditions
Keywords
End Stage Kidney Disease (ESKD), Myocardial infarction (MI), Atherosclerotic cardiovascular disease (ASCVD), Coronary artery disease, Peripheral artery disease, Diabetes
Brief summary
This is a two-part, phase 2b and phase 3 combined 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 vs placebo 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.
Interventions
DRUGCSL300
IV administration
DRUGPlacebo
Matching the excipient content and concentration of the CSL300 product, minus the active ingredient.
Sponsors
CSL Behring
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* Subjects who participated in Part 1 (phase 2b) are not eligible to participate in Part 2 (phase 3). * Concomitant use of systemic immunosuppressant drugs. * Part 1 (Phase 2b) excludes subjects with a positive TB or a history of latent TB, whereas Part 2 (Phase 3) excludes active TB but allows inclusion of subjects with a latent TB and at least 4 weeks of prophylactic TB treatment. * 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b) | Baseline and up to Week 12 |
| Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3) | Approximately 5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 Week 24 | — |
| Mean change from Baseline in serum amyloid A (SAA) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in secretory phospholipase A2 (sPLA2) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in fibrinogen (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in plasminogen activator inhibitor -1 (PAI-1) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in lipoprotein (Lp) (a) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in albumin (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in Hepcidin (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in hemoglobin (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in erythropoiesis-stimulating agents (ESA) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in erythropoietin-resistance index (ERI) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in iron (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in total iron binding capacity (TIBC) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in transferrin saturation (TSAT) (Phase 2b) | Baseline and up to Week 12 | — |
| Mean change from Baseline in ferritin (Phase 2b) | Baseline and up to Week 12 | — |
| Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b) | Up to Week 24 | — |
| Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b) | Up to Week 24 | — |
| Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b) | Up to Week 24 | — |
| Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b) | Up to Week 24 | — |
| Percent of participants with adverse events (AE), serious AE (SAE), including adverse events of special interest (AESIs) (Phase 2b) | Up to Week 32 | — |
| Mean change from Baseline in white blood cell (WBC) (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in neutrophils (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in platelets (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in aspartate aminotransferase (AST) (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in alanine aminotransferase (ALT) (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in total bilirubin (Phase 2b) | Up to Week 12 | — |
| Mean change from Baseline in lipid panel (Phase 2b) | Up to Week 12 | 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 Week 12 | — |
| 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) | Up to 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 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Denmark, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Romania, Slovakia, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTTrial Registration Coordinator
STUDY_DIRECTORStudy Director
CSL Behring LLC
Outcome results
None listed