Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition
- Conditions
- Chronic Kidney DiseasesInflammation
- Interventions
- Biological: Ziltivekimab
- Registration Number
- NCT03926117
- Lead Sponsor
- Novo Nordisk A/S
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 264
- 18 years of age
- Stage 3-5 CKD
- hs-CRP > 2.0 mg/L
- Comply with contraception
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Ziltivekimab Matching placebo Ziltivekimab 15 mg Ziltivekimab - Ziltivekimab 30 mg Ziltivekimab - Ziltivekimab 7.5 mg Ziltivekimab -
- Primary Outcome Measures
Name Time Method Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels Baseline (average of the hs-CRP value prior to randomization and day 1), week 13 Percent change from baseline in hs-CRP levels at week 13 are presented.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Fibrinogen Baseline (day 1), week 13 Percent change from baseline in fibrinogen at week 13 are presented.
Percent Change From Baseline in Serum Amyloid A (SAA) Baseline (average of the values at week -1 and day 1), week 13 Percent change from baseline in SAA at week 13 are presented.
Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events From week 0 to week 32 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.
Change in Systolic Blood Pressure (SBP) Baseline (week 1), week 32 Change from baseline in systolic blood pressure at week 32 are presented.
Change in Diastolic Blood Pressure (DBP) Baseline (week 1), week 32 Change from baseline in diastolic blood pressure at week 32 are presented.
Change in Respiratory Rate Baseline (week 1), week 32 Change from baseline in respiratory rate at week 32 are presented.
Change in Bicarbonate, Chloride, Potassium, Sodium Baseline (week 1), week 32 Change from baseline in bicarbonate, chloride, potassium, sodium at week 32 are presented.
Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen Baseline (week 1), week 32 Change from baseline in direct bilirubin, bilirubin, calcium, creatinine, glucose, phosphate and urea nitrogen at week 32 are presented.
Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) From week 0 to week 32 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.
Change in Body Mass Index (BMI) Baseline (week 1), week 24 Change from baseline in BMI at week 24 are presented.
Change in Temperature Baseline (week 1), week 32 Change from baseline in temperature at week 32 are presented.
Change in Electrocardiogram (ECG) Baseline (week -1), Week 24 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.
Change in Heart Rate Baseline (week 1), week 32 Change from baseline in heart rate at Week 32 are presented.
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 From week 0 to week 32 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.
Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels Baseline (week 1), week 32 Change from baseline in ALP, ALT and AAT levels at week 32 are presented.
Number of Participants With Anti-drug Antibodies (ADAs) From week 0 to week 32 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.
Follicle Stimulating Hormone (FSH) Levels Baseline (week -1) FSH levels at baseline (week -1) are presented.
Trial Locations
- Locations (1)
Novo Nordisk Investigational Site
🇺🇸Kenosha, Wisconsin, United States