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

• ClinicalTrials.gov Identifier: NCT05485961
• Recruitment Status: Recruiting
• First Posted: August 3, 2022
• Last Update Posted: February 6, 2023
• Sponsor: CSL Behring
• Information provided by (Responsible Party): CSL Behring

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 (Clinical Trial)
• Estimated 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
• Actual Study Start Date: October 21, 2022
• Estimated Primary Completion Date: December 2028
• Estimated Study Completion Date: December 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 Name: 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 Name: 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 Name: 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 Name: Clazakizumab
Placebo Comparator: Placebo (Phase 3); IV administration	Drug: Placebo; 0.9% w/v NaCl

Outcome Measures

Primary Outcome Measures :

1. Change from Baseline on the log scale in high-sensitivity C-reactive protein (hs-CRP)(Phase 2b) [ Time Frame: Up to 12 weeks ]
2. Time to first occurrence of CV death or MI (Phase 3) [ Time Frame: Approximately 5 years ]

Secondary Outcome Measures :

1. Percent of subjects achieving hs-CRP < 2.0 mg/L (Phase 2b) [ Time Frame: Week 12 ]
2. Change from baseline in log-transformed hs-CRP (Phase 2b) [ Time Frame: Up to 24 weeks ]
3. Mean change from Baseline in SAA (Phase 2b) [ Time Frame: Up to 12 weeks ]
4. Mean change from Baseline in sPLA2 (Phase 2b) [ Time Frame: Up to 12 weeks ]
5. Mean change from Baseline in fibrinogen (Phase 2b) [ Time Frame: Up to 12 weeks ]
6. Mean change from Baseline in PAI-1 (Phase 2b) [ Time Frame: Up to 12 weeks ]
7. Mean change from Baseline in Lp (a) (Phase 2b) [ Time Frame: Up to 12 weeks ]
8. Mean change from Baseline in Hepcidin (Phase 2b) [ Time Frame: Up to 12 weeks ]
9. Mean change from Baseline in hemoglobin (Phase 2b) [ Time Frame: Up to 12 weeks ]
10. Mean change from Baseline in ESA (Phase 2b) [ Time Frame: Up to 12 weeks ]
11. Mean change from Baseline in ERI (Phase 2b) [ Time Frame: Up to 12 weeks ]
12. Mean change from Baseline in iron (Phase 2b) [ Time Frame: Up to 12 weeks ]
13. Mean change from Baseline in TIBC (Phase 2b) [ Time Frame: Up to 12 weeks ]
14. Mean change from Baseline in TSAT (Phase 2b) [ Time Frame: Up to 12 weeks ]
15. Mean change from Baseline in ferritin (Phase 2b) [ Time Frame: Up to 12 weeks ]
16. Area under the plasma concentration versus time curve (AUC) for CSL300 (Phase 2b) [ Time Frame: Up to 24 weeks ]
17. Peak Plasma Concentration (Cmax) for CSL300 (Phase 2b) [ Time Frame: Up to 24 weeks ]
18. Trough Plasma Concentration (Ctrough) for CSL300 (Phase 2b) [ Time Frame: Up to 24 weeks ]
19. Time to Maximum Plasma Concentration (Tmax) for CSL300 (Phase 2b) [ Time Frame: Up to 24 weeks ]
20. Percent of subjects with AE, SAE, including AESIs (Phase 2b) [ Time Frame: Up to 32 weeks ]
21. Mean change from Baseline in WBC (Phase 2b) [ Time Frame: Up to 12 weeks ]
22. Mean change from Baseline in neutrophils (Phase 2b) [ Time Frame: Up to 12 weeks ]
23. Mean change from Baseline in platelets (Phase 2b) [ Time Frame: Up to 12 weeks ]
24. Mean change from Baseline in AST (Phase 2b) [ Time Frame: Up to 12 weeks ]
25. Mean change from Baseline in ALT (Phase 2b) [ Time Frame: Up to 12 weeks ]
26. Mean change from Baseline in total bilirubin (Phase 2b) [ Time Frame: Up to 12 weeks ]
27. Mean change from Baseline in lipid panel (Phase 2b) [ Time Frame: Up to 12 weeks ]
    Lipid panel consists of TC, LDL-C, HDL-C, triglyceride
28. Titer of confirmed antibodies specific to CSL300 (Phase 2b) [ Time Frame: Up to 12 weeks ]
29. Time to first occurrence of all-cause death or MI (Phase 3) [ Time Frame: Approximately 5 years ]
30. Time to first occurrence of CV death, MI, or ischemic stroke (Phase 3) [ Time Frame: Approximately 5 years ]
31. Time to first occurrence of CV death (Phase 3) [ Time Frame: Approximately 5 years ]
32. Time to first occurrence of CV death, MI or major adverse limb event (Phase 3) [ Time Frame: Approximately 5 years ]
33. Time to first occurrence of all-cause death (Phase 3) [ Time Frame: Approximately 5 years ]
34. Time to first occurrence of CV death, MI, or hospitalization for heart failure (Phase 3) [ Time Frame: Approximately 5 years ]
35. Total number of CV hospitalizations (Phase 3) [ Time Frame: Approximately 5 years ]
36. Total number of HF hospitalizations and urgent visits (Phase 3) [ Time Frame: Approximately 5 years ]
37. Total number of hospitalizations (Phase 3) [ Time Frame: Approximately 5 years ]

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Trial Registration Coordinator; 610-878-4000; clinicaltrials@cslbehring.com

Locations

United States, Virginia

Peninsula Kidney Associates; Recruiting

Hampton, Virginia, United States, 23666

Contact: Use Central Contact

Sponsors and Collaborators

CSL Behring

Investigators

• Study Director: Study Director; CSL Behring LLC

More Information

• Responsible Party: CSL Behring
• ClinicalTrials.gov Identifier: NCT05485961
• Other Study ID Numbers: CSL300_2301; 2022-500273-14-00 ( Other Identifier: EU CT )
• First Posted: August 3, 2022
• Last Update Posted: February 6, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• 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.

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.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CSL Behring:

End Stage Kidney Disease (ESKD); Myocardial infarction (MI); Atherosclerotic cardiovascular disease (ASCVD); Coronary artery disease; Peripheral artery disease; Diabetes

Additional relevant MeSH terms:

Kidney Diseases; Kidney Failure, Chronic; Cardiovascular Diseases; Atherosclerosis; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases