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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
264
human IgG1k anti-human IL-6 monoclonal antibody
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.
Time frame: Baseline (average of the hs-CRP value prior to randomization and day 1), week 13
Percent Change From Baseline in Serum Amyloid A (SAA)
Percent change from baseline in SAA at week 13 are presented.
Time frame: 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.
Time frame: 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.
Time frame: From week 0 to week 32
Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Central Alabama Research
Birmingham, Alabama, United States
Aventiv Research
Mesa, Arizona, United States
Arizona Kidney Disease and Hypertension Center
Phoenix, Arizona, United States
Elite Clinical Studies
Phoenix, Arizona, United States
North America Research Institute
Lynwood, California, United States
North America Research Institute
Riverside, California, United States
Apex Research of Riverside
Riverside, California, United States
North America Research Institute
San Dimas, California, United States
Western Nephrology and Metabolic Bone Disease, PC
Arvada, Colorado, United States
AMPM Research Clinic
Miami, Florida, United States
...and 39 more locations
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.
Time frame: 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.
Time frame: From week 0 to week 32
Change in Systolic Blood Pressure (SBP)
Change from baseline in systolic blood pressure at week 32 are presented.
Time frame: Baseline (week 1), week 32
Change in Diastolic Blood Pressure (DBP)
Change from baseline in diastolic blood pressure at week 32 are presented.
Time frame: Baseline (week 1), week 32
Change in Respiratory Rate
Change from baseline in respiratory rate at week 32 are presented.
Time frame: Baseline (week 1), week 32
Change in Body Mass Index (BMI)
Change from baseline in BMI at week 24 are presented.
Time frame: Baseline (week 1), week 24
Change in Heart Rate
Change from baseline in heart rate at Week 32 are presented.
Time frame: Baseline (week 1), week 32
Change in Temperature
Change from baseline in temperature at week 32 are presented.
Time frame: 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.
Time frame: 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.
Time frame: Baseline (week 1), week 32
Change in Bicarbonate, Chloride, Potassium, Sodium
Change from baseline in bicarbonate, chloride, potassium, sodium at week 32 are presented.
Time frame: 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.
Time frame: Baseline (week 1), week 32
Follicle Stimulating Hormone (FSH) Levels
FSH levels at baseline (week -1) are presented.
Time frame: 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.
Time frame: From week 0 to week 32