Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis

Sponsor

CSL Behring (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05485961

Collaborator

(none)

2,310

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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 end stage kidney disease (ESKD) undergoing maintenance dialysis with systemic inflammation and either atherosclerotic cardiovascular disease (ASCVD) or diabetes.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Cardiovascular Disease End Stage Kidney Disease	Drug: CSL300 Drug: Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2310 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

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

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2028

Anticipated Study Completion Date :

Dec 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CSL300 (low dose)(Phase 2b) Intravenous (IV) administration	Drug: CSL300 Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 Other Names: Clazakizumab
Experimental: CSL300 (medium dose)(Phase 2b) IV administration	Drug: CSL300 Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 Other Names: Clazakizumab
Experimental: CSL300 (high dose)(Phase 2b) IV administration	Drug: CSL300 Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 Other Names: Clazakizumab
Placebo Comparator: Placebo (Phase 2b) IV administration	Drug: Placebo 0.9% w/v NaCl
Experimental: CSL300 (Phase 3) IV administration	Drug: CSL300 Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6 Other Names: Clazakizumab
Placebo Comparator: Placebo (Phase 3) IV administration	Drug: Placebo 0.9% w/v NaCl

Outcome Measures

Primary Outcome Measures

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

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]
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 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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