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

Primary Purpose

Atherosclerotic Cardiovascular Disease, End Stage Kidney Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CSL300
Placebo
Placebo
Sponsored by
CSL Behring
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Atherosclerotic Cardiovascular Disease focused on measuring End Stage Kidney Disease (ESKD), Myocardial infarction (MI), Atherosclerotic cardiovascular disease (ASCVD), Coronary artery disease, Peripheral artery disease, Diabetes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Peninsula Kidney AssociatesRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Experimental

Placebo Comparator

Arm Label

CSL300 (low dose)(Phase 2b)

CSL300 (medium dose)(Phase 2b)

CSL300 (high dose)(Phase 2b)

Placebo (Phase 2b)

CSL300 (Phase 3)

Placebo (Phase 3)

Arm Description

Intravenous (IV) administration

IV administration

IV administration

IV administration

IV administration

IV administration

Outcomes

Primary Outcome Measures

Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
Time to first occurrence of CV death or MI (Phase 3)

Secondary Outcome Measures

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

Full Information

First Posted
July 29, 2022
Last Updated
June 21, 2023
Sponsor
CSL Behring
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1. Study Identification

Unique Protocol Identification Number
NCT05485961
Brief Title
Combined Dose-Finding and CV Outcomes Study With CSL300 (Clazakizumab) in Adult Subjects With ESKD Undergoing Dialysis
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 21, 2022 (Actual)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
CSL Behring

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atherosclerotic Cardiovascular Disease, End Stage Kidney Disease
Keywords
End Stage Kidney Disease (ESKD), Myocardial infarction (MI), Atherosclerotic cardiovascular disease (ASCVD), Coronary artery disease, Peripheral artery disease, Diabetes

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
2310 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CSL300 (low dose)(Phase 2b)
Arm Type
Experimental
Arm Description
Intravenous (IV) administration
Arm Title
CSL300 (medium dose)(Phase 2b)
Arm Type
Experimental
Arm Description
IV administration
Arm Title
CSL300 (high dose)(Phase 2b)
Arm Type
Experimental
Arm Description
IV administration
Arm Title
Placebo (Phase 2b)
Arm Type
Placebo Comparator
Arm Description
IV administration
Arm Title
CSL300 (Phase 3)
Arm Type
Experimental
Arm Description
IV administration
Arm Title
Placebo (Phase 3)
Arm Type
Placebo Comparator
Arm Description
IV administration
Intervention Type
Drug
Intervention Name(s)
CSL300
Other Intervention Name(s)
Clazakizumab
Intervention Description
Clazakizumab is a genetically engineered humanized immunoglobulin G1 (IgG1) mAb that binds to human IL-6
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% w/v NaCl
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Part 2 (Phase 3): Matching the excipient content and concentration of the CSL300 product, minus the active ingredient
Primary Outcome Measure Information:
Title
Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b)
Time Frame
Up to 12 weeks
Title
Time to first occurrence of CV death or MI (Phase 3)
Time Frame
Approximately 5 years
Secondary Outcome Measure Information:
Title
Percent of subjects achieving hs-CRP < 2.0 mg/L (Phase 2b)
Time Frame
Week 12
Title
Change from baseline in log-transformed hs-CRP (Phase 2b)
Time Frame
Up to 24 weeks
Title
Mean change from Baseline in SAA (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in sPLA2 (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in fibrinogen (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in PAI-1 (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in Lp (a) (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in Hepcidin (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in hemoglobin (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in ESA (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in ERI (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in iron (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in TIBC (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in TSAT (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in ferritin (Phase 2b)
Time Frame
Up to 12 weeks
Title
Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b)
Time Frame
Up to 24 weeks
Title
Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b)
Time Frame
Up to 24 weeks
Title
Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b)
Time Frame
Up to 24 weeks
Title
Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b)
Time Frame
Up to 24 weeks
Title
Percent of subjects with AE, SAE, including AESIs (Phase 2b)
Time Frame
Up to 32 weeks
Title
Mean change from Baseline in WBC (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in neutrophils (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in platelets (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in AST (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in ALT (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in total bilirubin (Phase 2b)
Time Frame
Up to 12 weeks
Title
Mean change from Baseline in lipid panel (Phase 2b)
Description
Lipid panel consists of TC, LDL-C, HDL-C, triglyceride
Time Frame
Up to 12 weeks
Title
Titer of confirmed antibodies specific to CSL300 (Phase 2b)
Time Frame
Up to 12 weeks
Title
Time to first occurrence of all-cause death or MI (Phase 3)
Time Frame
Approximately 5 years
Title
Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3)
Time Frame
Approximately 5 years
Title
Time to first occurrence of CV death (Phase 3)
Time Frame
Approximately 5 years
Title
Time to first occurrence of CV death, MI or major adverse limb event (Phase 3)
Time Frame
Approximately 5 years
Title
Time to first occurrence of all-cause death (Phase 3)
Time Frame
Approximately 5 years
Title
Time to first occurrence of CV death, MI, or hospitalization for heart failure (Phase 3)
Time Frame
Approximately 5 years
Title
Total number of CV hospitalizations (Phase 3)
Time Frame
Approximately 5 years
Title
Total number of HF hospitalizations and urgent visits (Phase 3)
Time Frame
Approximately 5 years
Title
Total number of hospitalizations (Phase 3)
Time Frame
Approximately 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Trial Registration Coordinator
Phone
610-878-4000
Email
clinicaltrials@cslbehring.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
CSL Behring LLC
Official's Role
Study Director
Facility Information:
Facility Name
Peninsula Kidney Associates
City
Hampton
State/Province
Virginia
ZIP/Postal Code
23666
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Use Central Contact

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.

Learn more about this trial

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

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