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

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

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 ASCVD or diabetes mellitus and evidence of systemic inflammation who are undergoing maintenance dialysis.

Study Overview

• Status: Active, not recruiting
• Conditions: End Stage Kidney Disease; Atherosclerotic Cardiovascular Disease
• Intervention / Treatment: Drug: CSL300; Drug: Placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 2310
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Trial Registration Coordinator; Phone Number: 610-878-4000; Email: clinicaltrials@cslbehring.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia, 2139
      • 03600017 - Concord Repatriation General Hospital
  • Queensland
    • Nambour, Queensland, Australia, 4560
      • 03600021 - Sunshine Coast University Private Hospital
    • Woolloongabba, Queensland, Australia, 4102
      • 03600014 - Princess Alexandra Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • 03600013 - Monash Medical Centre
    • St Albans, Victoria, Australia, 3021
      • 03600011 - Sunshine Hospital
• Belgium
  • Aalst, Belgium, 9300
    • 05600011 - Onze-Lieve-Vrouwziekenhuis VZW
  • Bonheiden, Belgium, 2820
    • 05600005 - Imelda Ziekenhuis
  • Gent, Belgium, 9000
    • 05600004 - AZ Sint-Lucas
  • Leuven, Belgium, 3000
    • 05600012 - Universitair Ziekenhuis Leuven
  • Liège, Belgium, 4000
    • 05600003 - CHR de la Citadelle
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G2P4
      • 12400008 - University of Alberta Hospital
• Germany
  • Kiel, Germany, 24105
    • 27600022 - UKSH - Universitatsklinik Schleswig-Holstein
  • Villingen-Schwenningen, Germany, 78052
    • 27600020 - Nephrologisches Zentrum Villingen-Schwenningen
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • 84000149 - Nephrology Consultants, LLC
  • Arizona
    • Glendale, Arizona, United States, 91206
      • 84000178 - Kidney Disease Medical Group
    • Phoenix, Arizona, United States, 85018
      • 84000231 - AKDHC Medical
    • Tucson, Arizona, United States, 85705
      • 84000286 - AKDHC Medical
  • California
    • Bakersfield, California, United States, 93309
      • 84000145 - National Institute of Clinical Research
    • Bakersfield, California, United States, 93309
      • 84000151 - National Institute of Clinical Research
    • Beverly Hills, California, United States, 90211
      • 84000277 - Amicis Research Center
    • Chula Vista, California, United States, 91910
      • 84000241 - California Institute of Renal Research
    • Glendale, California, United States, 91206
      • 84000230 - Kidney Disease Medical Group
    • La Mesa, California, United States, 91942
      • 84000235 - California Institute of Renal Research
    • La Palma, California, United States, 90623
      • 84000198 - Southern California Medical Research Center
    • Los Angeles, California, United States, 90033
      • 84000158 - DaVita Carabello Dialysis Center
    • Lynwood, California, United States, 90262
      • 84000175 - Renal Medical Associates/NARI
    • Northridge, California, United States, 91324
      • 84000279 - Amicis Research Center
    • San Diego, California, United States, 92123
      • 84000143 - California Institute of Renal Research
    • San Diego, California, United States, 92111
      • 84000238 - California Institute of Renal Research
    • San Jose, California, United States, 95126
      • 84000281 - Satellite Healthcare
    • Vacaville, California, United States, 95687
      • 84000278 - Amicis Research Center
    • Victorville, California, United States, 92394
      • 84000174 - DaVita Vista Del Sol Dialysis
  • Colorado
    • Denver, Colorado, United States, 80230
      • 84000223 - Colorado Kidney Care
  • Connecticut
    • Bloomfield, Connecticut, United States, 06002
      • 84000176 - Greater Hartford Nephrology, LLC
    • Middlebury, Connecticut, United States, 06762
      • 84000173 - Nephrology and Hypertension Associates PC
  • Florida
    • Coral Gables, Florida, United States, 33134
      • 84000193 - Horizon Research Group LLC
    • Lauderdale Lakes, Florida, United States, 33313
      • 84000140 -South Florida Research Institute
    • Miami, Florida, United States, 33173
      • 84000182 - Nephrology Associates of South Miami
    • Tampa, Florida, United States, 33603
      • 84000139 - Genesis Clinical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • 84000157 - Renal Associates LLC
    • Statesboro, Georgia, United States, 30458
      • 84000194 - Atekha Nephrology Clinic LLC
  • Michigan
    • Roseville, Michigan, United States, 48066
      • 84000171 - St. Clair Nephrology Research
    • Saint Clair Shores, Michigan, United States, 48081
      • 84000237 - Center for Advanced Kidney Research, PLC
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • 84000146 - DCR Edina
  • Mississippi
    • Brookhaven, Mississippi, United States, 39601
      • 84000225 - Southwest Mississippi Nephrology PLLC
    • Tupelo, Mississippi, United States, 38801
      • 84000144 - Nephrology and Hypertension Associates Ltd
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • 84000147 - Clinical Research Consultants
  • Nebraska
    • North Platte, Nebraska, United States, 69101
      • 84000222 - Great Plains Health - Nephrology
  • New Hampshire
    • Portsmouth, New Hampshire, United States, 03801
      • 84000141 - Seacoast Kidney and Hypertension Specialists
  • New York
    • Bronx, New York, United States, 10461
      • 84000155 - DaVita Clinic Research Bronx
    • College Point, New York, United States, 11356
      • 84000184 - Mattoo & Bhat Medical Associates, P.C.
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • 84000191 - Metrolina Nephrology Associates, PA
    • Durham, North Carolina, United States, 27704
      • 84000150 - Durham Nephrology Associates, PA
    • Greenville, North Carolina, United States, 27858
      • 84000232 - East Carolina University
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18017
      • 84000234 - Northeast Clinical Research Center, LLC
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • 84000192 - Columbia Nephrology
    • Spartanburg, South Carolina, United States, 29306
      • 84000229 - DaVita Clinical Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • 84000180 - Knoxville Kidney Center PLLC
  • Virginia
    • Hampton, Virginia, United States, 23666
      • 84000138 - Peninsula Kidney Associates
    • Norfolk, Virginia, United States, 23502
      • 84000156 - Tidewater Kidney Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / 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; Drug: Placebo; Part 2 (Phase 3): Matching the excipient content and concentration of the CSL300 product, minus the active ingredient
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; Drug: Placebo; Part 2 (Phase 3): Matching the excipient content and concentration of the CSL300 product, minus the active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Measure Description	Time Frame
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)	Lipid panel consists of TC, LDL-C, HDL-C, triglyceride	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 (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

Collaborators and Investigators

• Sponsor: CSL Behring
• Investigators: Study Director: Study Director, CSL Behring LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2022
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: July 29, 2022
• First Submitted That Met QC Criteria: August 1, 2022
• First Posted (Actual): August 3, 2022

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Diabetes; Coronary artery disease; Peripheral artery disease; End Stage Kidney Disease (ESKD); Myocardial infarction (MI); Atherosclerotic cardiovascular disease (ASCVD)
• Additional Relevant MeSH Terms: Pathologic Processes; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Renal Insufficiency, Chronic; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Diseases; Kidney Diseases; Kidney Failure, Chronic; Atherosclerosis
• Other Study ID Numbers: CSL300_2301; 2022-500273-14-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: CSL will consider on a case-by-case basis requests to share Individual Patient Data (IPD) with external bona-fide, qualified scientific and medical researchers. For information on the process and requirements for submitting a voluntary data sharing request for IPD, please contact CSL at clinicaltrials@cslbehring.com.
• IPD Sharing Time Frame: Requests for IPD will generally be considered once review by major regulatory authorities (ie FDA, EMA) is complete and the primary publication is available.

IPD Sharing Access Criteria

Proposed research should seek to answer a previously unanswered important medical or scientific question.

Applicable country specific privacy and other laws and regulations will be considered and may prevent sharing of IPD.

If the request is approved and the researcher has executed an appropriate data sharing agreement, IPD that has been appropriately anonymized will be available.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No