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.
Brief Title
Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis
Categories
Central Contacts
Central Contact Role
Contact
Central Contact Phone
+1 610-878-4697
Central Contact Email
clinicaltrials@cslbehring.com
Completion Date
Completion Date Type
Estimated
Conditions
Atherosclerotic Cardiovascular Disease
End Stage Kidney Disease
Atherosclerotic Cardiovascular Disease in Patients With ESKD
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Keywords
End Stage Kidney Disease (ESKD)
Myocardial infarction (MI)
Atherosclerotic cardiovascular disease (ASCVD)
Coronary artery disease
Peripheral artery disease
Diabetes
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05485961
Org Class
Industry
Org Full Name
CSL Behring
Org Study Id
CSL300_2301
Overall Status
Recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Measure
Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Time to first occurrence of CV death or myocardial infarction (MI) (Phase 3)
Outcome Time Frame
Approximately 5 years
Secondary Ids
Secondary Id
2022-500273-14-00
Secondary Outcomes
Outcome Time Frame
Week 12
Outcome Measure
Percent of participants achieving hs-CRP less than (<) 2.0 milligram per Liter (mg/L) (Phase 2b)
Outcome Time Frame
Baseline and up to 24 weeks
Outcome Measure
Change from baseline in log-transformed hs-CRP (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in serum amyloid A (SAA) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in secretory phospholipase A2 (sPLA2) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in fibrinogen (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in plasminogen activator inhibitor -1 (PAI-1) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in lipoprotein (Lp) (a) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in albumin (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in Hepcidin (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in hemoglobin (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in erythropoiesis-stimulating agents (ESA) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in erythropoietin-resistance index (ERI) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in iron (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in total iron binding capacity (TIBC) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in transferrin saturation (TSAT) (Phase 2b)
Outcome Time Frame
Baseline and up to 12 weeks
Outcome Measure
Mean change from Baseline in ferritin (Phase 2b)
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b)
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b)
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b)
Outcome Time Frame
Up to 24 weeks
Outcome Measure
Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b)
Outcome Time Frame
Up to 32 weeks
Outcome Measure
Percent of participants with adverse events (AE), serious AE (SAE), including adverse events of special interest (AESIs) (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in white blood cell (WBC) (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in neutrophils (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in platelets (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in aspartate aminotransferase (AST) (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in alanine aminotransferase (ALT) (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in total bilirubin (Phase 2b)
Outcome Description
Lipid panel consists of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride.
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Mean change from Baseline in lipid panel (Phase 2b)
Outcome Time Frame
Up to 12 weeks
Outcome Measure
Titer of confirmed antibodies specific to CSL300 (Phase 2b)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of all-cause death or MI (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death, MI or major adverse limb event (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of all-cause death (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Time to first occurrence of CV death, MI, or hospitalization for heart failure (HF) (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of CV hospitalizations (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of HF hospitalizations and urgent visits (Phase 3)
Outcome Time Frame
Approximately 5 years
Outcome Measure
Total number of hospitalizations (Phase 3)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Matthew Abramowitz
Investigator Email
matthew.abramowitz@einsteinmed.org