Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition

Study Overview
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Brief Summary
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Patients with chronic kidney disease, who have evidence of systemic inflammation with increased cardiovascular risk, will be enrolled into this trial. The purpose of this trial is to determine a dose to select for a potential cardiovascular outcome trial with Ziltivekimab. Doses to be tested will be 7.5 mg, 15 mg and 30 mg subcutaneous monthly compared to placebo for six months.

Official Title
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A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition

Conditions
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Chronic Kidney Diseases, Inflammation

Intervention / Treatment
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* Biological: Ziltivekimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age Stage 3-5 CKD hs-CRP > 2.0 mg/L Comply with contraception Exclusion Criteria: Low neutrophil count Low platelet count Spot urine protein to creatinine ration > 4000 mg/g ALT/AST >2.5x ULN TSAT < 10% Positive TB test Evidence of HIV, hepatitis B Blind or illiterate Expected to require blood transfusion Thromboembolic event within 12-weeks Evidence of active infection Peptic ulcer disease, diverticulitis, inflammatory bowel disease Uncontrolled hypertension Planned coronary revascularization Major cardiac surgery, CHF Active malignancy, bone marrow or organ transplant Allergy to study drug Treatment with investigational drug, treatment with HIF stabilizer or ESA Use of immunosuppressive drugs, systemic antibiotics Breastfeeding, any other significant medical history

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Matching placebo | Biological: Ziltivekimab<br>* human IgG1k anti-human IL-6 monoclonal antibody<br>* Other names: COR-001;|
| Experimental: Ziltivekimab 7.5 mg<br> | Biological: Ziltivekimab<br>* human IgG1k anti-human IL-6 monoclonal antibody<br>* Other names: COR-001;|
| Experimental: Ziltivekimab 15 mg<br> | Biological: Ziltivekimab<br>* human IgG1k anti-human IL-6 monoclonal antibody<br>* Other names: COR-001;|
| Experimental: Ziltivekimab 30 mg<br> | Biological: Ziltivekimab<br>* human IgG1k anti-human IL-6 monoclonal antibody<br>* Other names: COR-001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels | Percent change from baseline in hs-CRP levels at week 13 are presented. | Baseline (average of the hs-CRP value prior to randomization and day 1), week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Serum Amyloid A (SAA) | Percent change from baseline in SAA at week 13 are presented. | Baseline (average of the values at week -1 and day 1), week 13 | 
| Percent Change From Baseline in Fibrinogen | Percent change from baseline in fibrinogen at week 13 are presented. | Baseline (day 1), week 13 | 
| Percentage of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious AEs (TESAEs), Severe Hematologic AEs, Severe Non-hematologic AEs, and AEs Leading to Drug Discontinuation | An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. TEAEs are defined as AEs that initiated or worsened on or after the date of first dose of study drug up to the end of safety-follow-up. A SAE was defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. TEAEs that met any of these criteria were considered severe hematologic AEs: grade 3 neutropenia, grade 3 anemia, grade 3 leukopenia, grade 3 lymphopenia, grade 3 eosinophilia, and grade 3 thrombocytopenia. | From week 0 to week 32 | 
| Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events | Bleeding events were classified using the TIMI bleeding classification as follows: 1) major: intracranial hemorrhage or a >=5 g/dL decrease in the hemoglobin concentration or a >=15 percent (%) absolute decrease in the hematocrit; 2) minor: (a) observed blood loss: >=3 g/dL decrease in the hemoglobin concentration or >=10% decrease in the hematocrit. (b) no observed blood loss: >=4 g/dL decrease in the hemoglobin concentration or >=12% decrease in the hematocrit; 3) minimal: any clinically overt sign of hemorrhage (including imaging) that was associated with a < 3 g/dL decrease in the hemoglobin concentration or <9% decrease in the hematocrit. | From week 0 to week 32 | 
| Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. AESI included serious infections, malignancies, anaphylaxis occurring at any time, even if considered unrelated to the study drug, gastrointestinal perforations, hypersensitivity reaction during investigational product (IP) administration, neutrophils per cubic millimeter (500/mm^3) (severe) or neutrophils <1000/mm^3 (severe) with evidence of concurrent infection, severe injection-related reactions, thrombocytopenia (platelet count <50,000/mm^3 (severe)) or platelet count <75,000/mm^3 (moderate) with evidence of concurrent TIMI major bleeding. | From week 0 to week 32 | 
| Change in Systolic Blood Pressure (SBP) | Change from baseline in systolic blood pressure at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Diastolic Blood Pressure (DBP) | Change from baseline in diastolic blood pressure at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Respiratory Rate | Change from baseline in respiratory rate at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Body Mass Index (BMI) | Change from baseline in BMI at week 24 are presented. | Baseline (week 1), week 24 | 
| Change in Heart Rate | Change from baseline in heart rate at Week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Temperature | Change from baseline in temperature at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Electrocardiogram (ECG) | The ECG was assessed by the investigator at baseline (week -1) and week 24 and categorised as abnormal clinically significant, abnormal not clinically significant, indeterminate, normal, not evaluable and unknown. Number of participants in each ECG category at baseline and week 24 are presented. | Baseline (week -1), Week 24 | 
| Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | Change from baseline in ALP, ALT and AAT levels at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Bicarbonate, Chloride, Potassium, Sodium | Change from baseline in bicarbonate, chloride, potassium, sodium at week 32 are presented. | Baseline (week 1), week 32 | 
| Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Change from baseline in direct bilirubin, bilirubin, calcium, creatinine, glucose, phosphate and urea nitrogen at week 32 are presented. | Baseline (week 1), week 32 | 
| Follicle Stimulating Hormone (FSH) Levels | FSH levels at baseline (week -1) are presented. | Baseline (week -1) | 
| Number of Participants With Anti-drug Antibodies (ADAs) | Participants who had at least 1 positive sample (treatment-boosted or treatment-induced) at any time after their first Ziltivekimab administration were classified as positive for ADAs. In the instance that a participant had a positive sample at the baseline visit, the participant was considered positive only if the peak titer of the post-treatment sample was at least 2-fold higher (i.e., >=2-fold) than the titer of the baseline sample. Number of participants positive for antibodies to Ziltivekimab are presented. | From week 0 to week 32 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IL-6, CRP, Chronic Kidney Disease, Cardiovascular Disease, Inflammation