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

Atherosclerotic Cardiovascular Disease Clinical Trial

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05485961
• Other study ID #: CSL300_2301
• Secondary ID: 2022-500273-14-0
• Status: Enrolling by invitation
• Phase: Phase 2/Phase 3
• Start date: October 21, 2022
• Est. completion date: December 2028

Study information

• Verified date: June 2024
• Source: CSL Behring
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 2310
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• End Stage Kidney Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Drug:
• CSL300
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
• Placebo
0.9% w/v NaCl
• Placebo
Part 2 (Phase 3): Matching the excipient content and concentration of the CSL300 product, minus the active ingredient

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
CSL Behring

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)		Up to 12 weeks
Primary	Time to first occurrence of CV death or MI (Phase 3)		Approximately 5 years
Secondary	Percent of subjects achieving hs-CRP < 2.0 mg/L (Phase 2b)		Week 12
Secondary	Change from baseline in log-transformed hs-CRP (Phase 2b)		Up to 24 weeks
Secondary	Mean change from Baseline in SAA (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in sPLA2 (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in fibrinogen (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in PAI-1 (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in Lp (a) (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in Hepcidin (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in hemoglobin (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in ESA (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in ERI (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in iron (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in TIBC (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in TSAT (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in ferritin (Phase 2b)		Up to 12 weeks
Secondary	Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b)		Up to 24 weeks
Secondary	Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b)		Up to 24 weeks
Secondary	Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b)		Up to 24 weeks
Secondary	Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b)		Up to 24 weeks
Secondary	Percent of subjects with AE, SAE, including AESIs (Phase 2b)		Up to 32 weeks
Secondary	Mean change from Baseline in WBC (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in neutrophils (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in platelets (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in AST (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in ALT (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in total bilirubin (Phase 2b)		Up to 12 weeks
Secondary	Mean change from Baseline in lipid panel (Phase 2b)	Lipid panel consists of TC, LDL-C, HDL-C, triglyceride	Up to 12 weeks
Secondary	Titer of confirmed antibodies specific to CSL300 (Phase 2b)		Up to 12 weeks
Secondary	Time to first occurrence of all-cause death or MI (Phase 3)		Approximately 5 years
Secondary	Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3)		Approximately 5 years
Secondary	Time to first occurrence of CV death (Phase 3)		Approximately 5 years
Secondary	Time to first occurrence of CV death, MI or major adverse limb event (Phase 3)		Approximately 5 years
Secondary	Time to first occurrence of all-cause death (Phase 3)		Approximately 5 years
Secondary	Time to first occurrence of CV death, MI, or hospitalization for heart failure (Phase 3)		Approximately 5 years
Secondary	Total number of CV hospitalizations (Phase 3)		Approximately 5 years
Secondary	Total number of HF hospitalizations and urgent visits (Phase 3)		Approximately 5 years
Secondary	Total number of hospitalizations (Phase 3)		Approximately 5 years