NCT05485961
Recruiting
Phase 2
A Phase 2b / 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Combined Dose-Finding and Cardiovascular Outcome Study to Investigate the Efficacy and Safety of CSL300 (Clazakizumab) in Subjects With End Stage Kidney Disease Undergoing Dialysis
Overview
- Phase
- Phase 2
- Intervention
- CSL300
- Conditions
- Not specified
- Sponsor
- CSL Behring
- Enrollment
- 2310
- Locations
- 945
- Primary Endpoint
- Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
- Status
- Recruiting
- Last Updated
- 23 days ago
Overview
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.
Investigators
Eligibility Criteria
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
- •\- 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
Arms & Interventions
CSL300 (Phase 3)
IV administration
Intervention: CSL300
Placebo (Phase 2b)
IV administration
Intervention: Placebo
Placebo (Phase 3)
IV administration
Intervention: Placebo
CSL300 (medium dose)(Phase 2b)
IV administration
Intervention: CSL300
CSL300 (low dose)(Phase 2b)
Intravenous (IV) administration
Intervention: CSL300
CSL300 (high dose)(Phase 2b)
IV administration
Intervention: CSL300
Outcomes
Primary Outcomes
Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
Time Frame: Baseline and up to 12 weeks
Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3)
Time Frame: Approximately 5 years
Secondary Outcomes
- 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 erythropoiesis-stimulating agents (ESA) (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)
- 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)
Study Sites (945)
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