Chronic Kidney Diseases, Inflammation
Conditions
Keywords
IL-6, CRP, Chronic Kidney Disease, Cardiovascular Disease, Inflammation
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.
Interventions
BIOLOGICALZiltivekimab
human IgG1k anti-human IL-6 monoclonal antibody
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Matching placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fibrinogen | Baseline (day 1), week 13 | Percent change from baseline in fibrinogen at week 13 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. |
| 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. |
| 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 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 Body Mass Index (BMI) | Baseline (week 1), week 24 | Change from baseline in BMI at week 24 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. |
| 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 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. |
| 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. |
| Follicle Stimulating Hormone (FSH) Levels | Baseline (week -1) | FSH levels at baseline (week -1) 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. |
| Change in Heart Rate | Baseline (week 1), week 32 | Change from baseline in heart rate at Week 32 are presented. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 52 clinical sites in the United States.
Pre-assignment details
Participants were randomized 1:1:1:1 to one of three Ziltivekimab dose levels (7.5 milligram (mg), 15 mg, or 30 mg) or matching placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received subcutaneous (SC) injection of placebo matched to Ziltivekimab once in every 28 days at weeks 1, 5, 9, 13, 17 and 21. Participants were followed up for safety from week 25 through week 32. | 66 |
| Ziltivekimab 7.5 mg Participants received SC injection of 7.5 mg Ziltivekimab once in every 28 days at weeks 1, 5, 9, 13, 17 and 21. Participants were followed up for safety from week 25 through week 32. | 66 |
| Ziltivekimab 15 mg Participants received SC injection of 15 mg Ziltivekimab once in every 28 days at weeks 1, 5, 9, 13, 17 and 21. Participants were followed up for safety from week 25 through week 32. | 66 |
| Ziltivekimab 30 mg Participants received SC injection of 30 mg Ziltivekimab once in every 28 days at weeks 1, 5, 9, 13, 17 and 21. Participants were followed up for safety from week 25 through week 32. | 66 |
| Total | 264 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 | 3 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 | 0 |
| Overall Study | Randomized but not treated | 1 | 1 | 0 | 1 |
| Overall Study | Unclassified | 1 | 4 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Ziltivekimab 7.5 mg | Ziltivekimab 15 mg | Ziltivekimab 30 mg | Total |
|---|---|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 10.81 | 67.2 years STANDARD_DEVIATION 10.67 | 65.9 years STANDARD_DEVIATION 9.42 | 67.1 years STANDARD_DEVIATION 10.55 | 66.4 years STANDARD_DEVIATION 10.35 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 25 Participants | 12 Participants | 15 Participants | 19 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 54 Participants | 51 Participants | 46 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Race Black or African American | 16 Participants | 18 Participants | 12 Participants | 14 Participants | 60 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Race White | 50 Participants | 48 Participants | 49 Participants | 52 Participants | 199 Participants |
| Sex: Female, Male Female | 29 Participants | 32 Participants | 36 Participants | 32 Participants | 129 Participants |
| Sex: Female, Male Male | 37 Participants | 34 Participants | 30 Participants | 34 Participants | 135 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 65 | 0 / 65 | 0 / 66 | 0 / 65 |
| other Total, other adverse events | 19 / 65 | 22 / 65 | 18 / 66 | 17 / 65 |
| serious Total, serious adverse events | 10 / 65 | 13 / 65 | 9 / 66 | 8 / 65 |
Outcome results
Primary
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
Population: ITT analysis population included all randomized participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels | -4.49 Percent change |
| Ziltivekimab 7.5 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels | -76.57 Percent change |
| Ziltivekimab 15 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels | -88.12 Percent change |
| Ziltivekimab 30 mg | Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels | -91.64 Percent change |
Comparison: Percent change from baseline is analyzed using nonparametric Hodges-Lehmann estimator. The nonparametric analysis accounts for covariates baseline hemoglobin (greater than or equal to (\>=) 11 or less than (\<) 11 grams per deciliter (g/dL)) and chronic kidney disease stage (3, 4 or 5) by aligning responses within each stratum defined by the covariates prior to analysis.p-value: <0.000195% CI: [-86.15, -49.12]Hodges-Lehmann method
Comparison: Percent change from baseline is analyzed using nonparametric Hodges-Lehmann estimator. The nonparametric analysis accounts for covariates baseline hemoglobin (\>= 11 or \< 11 g/dL) and chronic kidney disease stage (3, 4 or 5) by aligning responses within each stratum defined by the covariates prior to analysis.p-value: <0.000195% CI: [-94.98, -62.97]Hodges-Lehmann method
Comparison: Percent change from baseline is analyzed using nonparametric Hodges-Lehmann estimator. The nonparametric analysis accounts for covariates baseline hemoglobin (\>= 11 or \< 11 g/dL) and chronic kidney disease stage (3, 4 or 5) by aligning responses within each stratum defined by the covariates prior to analysis.p-value: <0.000195% CI: [-101, -70.54]Hodges-Lehmann method
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALP: Change from baseline to Week 32 | -1.9 Units per liter (U/L) | Standard Deviation 14.75 |
| Placebo | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | AAT: Change from baseline to Week 32 | 0.6 Units per liter (U/L) | Standard Deviation 6.05 |
| Placebo | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALT: Change from baseline to Week 32 | 1.3 Units per liter (U/L) | Standard Deviation 5.53 |
| Ziltivekimab 7.5 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALT: Change from baseline to Week 32 | 2.6 Units per liter (U/L) | Standard Deviation 6.56 |
| Ziltivekimab 7.5 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALP: Change from baseline to Week 32 | -6.3 Units per liter (U/L) | Standard Deviation 18.28 |
| Ziltivekimab 7.5 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | AAT: Change from baseline to Week 32 | 2.3 Units per liter (U/L) | Standard Deviation 4.65 |
| Ziltivekimab 15 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALT: Change from baseline to Week 32 | 5.3 Units per liter (U/L) | Standard Deviation 11.76 |
| Ziltivekimab 15 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALP: Change from baseline to Week 32 | -9.6 Units per liter (U/L) | Standard Deviation 18.56 |
| Ziltivekimab 15 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | AAT: Change from baseline to Week 32 | 3.3 Units per liter (U/L) | Standard Deviation 8.28 |
| Ziltivekimab 30 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALP: Change from baseline to Week 32 | -15.7 Units per liter (U/L) | Standard Deviation 13.94 |
| Ziltivekimab 30 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | ALT: Change from baseline to Week 32 | 7.2 Units per liter (U/L) | Standard Deviation 13.73 |
| Ziltivekimab 30 mg | Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels | AAT: Change from baseline to Week 32 | 4.8 Units per liter (U/L) | Standard Deviation 9.15 |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Bicarbonate, Chloride, Potassium, Sodium | Bicarbonate: Change from baseline to Week 32 | -0.9 millimoles per liter (mmol/L) | Standard Deviation 2.6 |
| Placebo | Change in Bicarbonate, Chloride, Potassium, Sodium | Chloride: Change from baseline to Week 32 | 1.7 millimoles per liter (mmol/L) | Standard Deviation 3.86 |
| Placebo | Change in Bicarbonate, Chloride, Potassium, Sodium | Potassium: Change from baseline to Week 32 | 0.00 millimoles per liter (mmol/L) | Standard Deviation 0.445 |
| Placebo | Change in Bicarbonate, Chloride, Potassium, Sodium | Sodium: Change from baseline to Week 32 | 1.0 millimoles per liter (mmol/L) | Standard Deviation 2.92 |
| Ziltivekimab 7.5 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Sodium: Change from baseline to Week 32 | 0.0 millimoles per liter (mmol/L) | Standard Deviation 2.7 |
| Ziltivekimab 7.5 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Potassium: Change from baseline to Week 32 | -0.28 millimoles per liter (mmol/L) | Standard Deviation 0.739 |
| Ziltivekimab 7.5 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Chloride: Change from baseline to Week 32 | 0.0 millimoles per liter (mmol/L) | Standard Deviation 3.27 |
| Ziltivekimab 7.5 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Bicarbonate: Change from baseline to Week 32 | -0.3 millimoles per liter (mmol/L) | Standard Deviation 2.66 |
| Ziltivekimab 15 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Potassium: Change from baseline to Week 32 | -0.29 millimoles per liter (mmol/L) | Standard Deviation 0.57 |
| Ziltivekimab 15 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Sodium: Change from baseline to Week 32 | 0.3 millimoles per liter (mmol/L) | Standard Deviation 2.44 |
| Ziltivekimab 15 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Chloride: Change from baseline to Week 32 | 0.7 millimoles per liter (mmol/L) | Standard Deviation 2.95 |
| Ziltivekimab 15 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Bicarbonate: Change from baseline to Week 32 | -0.7 millimoles per liter (mmol/L) | Standard Deviation 2.96 |
| Ziltivekimab 30 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Chloride: Change from baseline to Week 32 | 0.9 millimoles per liter (mmol/L) | Standard Deviation 3.39 |
| Ziltivekimab 30 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Bicarbonate: Change from baseline to Week 32 | -1.2 millimoles per liter (mmol/L) | Standard Deviation 2.72 |
| Ziltivekimab 30 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Sodium: Change from baseline to Week 32 | -0.1 millimoles per liter (mmol/L) | Standard Deviation 2.2 |
| Ziltivekimab 30 mg | Change in Bicarbonate, Chloride, Potassium, Sodium | Potassium: Change from baseline to Week 32 | -0.16 millimoles per liter (mmol/L) | Standard Deviation 0.567 |
Secondary
Change in Body Mass Index (BMI)
Change from baseline in BMI at week 24 are presented.
Time frame: Baseline (week 1), week 24
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Body Mass Index (BMI) | 0.13 Kilograms per square meter (kg/m^2) | Standard Deviation 1.102 |
| Ziltivekimab 7.5 mg | Change in Body Mass Index (BMI) | 0.51 Kilograms per square meter (kg/m^2) | Standard Deviation 1.904 |
| Ziltivekimab 15 mg | Change in Body Mass Index (BMI) | 0.58 Kilograms per square meter (kg/m^2) | Standard Deviation 1.664 |
| Ziltivekimab 30 mg | Change in Body Mass Index (BMI) | 0.40 Kilograms per square meter (kg/m^2) | Standard Deviation 0.879 |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Diastolic Blood Pressure (DBP) | 0.7 mmHg | Standard Deviation 10.33 |
| Ziltivekimab 7.5 mg | Change in Diastolic Blood Pressure (DBP) | 2.9 mmHg | Standard Deviation 10.97 |
| Ziltivekimab 15 mg | Change in Diastolic Blood Pressure (DBP) | 1.1 mmHg | Standard Deviation 11.17 |
| Ziltivekimab 30 mg | Change in Diastolic Blood Pressure (DBP) | 3.1 mmHg | Standard Deviation 10.35 |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Direct Bilirubin: Change from baseline to Week 32 | -0.007 milligrams per deciliter (mg/dL) | Standard Deviation 0.0297 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Phosphate: Change from baseline to Week 32 | -0.04 milligrams per deciliter (mg/dL) | Standard Deviation 0.778 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Glucose: Change from baseline to Week 32 | -15.1 milligrams per deciliter (mg/dL) | Standard Deviation 83.48 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Bilirubin: Change from baseline to Week 32 | -0.028 milligrams per deciliter (mg/dL) | Standard Deviation 0.1284 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Urea Nitrogen: Change from baseline to Week 32 | 0.4 milligrams per deciliter (mg/dL) | Standard Deviation 11.76 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Calcium: Change from baseline to Week 32 | -0.04 milligrams per deciliter (mg/dL) | Standard Deviation 0.494 |
| Placebo | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Creatinine: Change from baseline to Week 32 | -0.041 milligrams per deciliter (mg/dL) | Standard Deviation 0.6114 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Phosphate: Change from baseline to Week 32 | 0.04 milligrams per deciliter (mg/dL) | Standard Deviation 0.766 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Creatinine: Change from baseline to Week 32 | 0.216 milligrams per deciliter (mg/dL) | Standard Deviation 0.5291 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Calcium: Change from baseline to Week 32 | 0.09 milligrams per deciliter (mg/dL) | Standard Deviation 0.407 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Glucose: Change from baseline to Week 32 | 8.9 milligrams per deciliter (mg/dL) | Standard Deviation 80.5 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Urea Nitrogen: Change from baseline to Week 32 | 4.7 milligrams per deciliter (mg/dL) | Standard Deviation 12.15 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Bilirubin: Change from baseline to Week 32 | 0.060 milligrams per deciliter (mg/dL) | Standard Deviation 0.1013 |
| Ziltivekimab 7.5 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Direct Bilirubin: Change from baseline to Week 32 | 0.008 milligrams per deciliter (mg/dL) | Standard Deviation 0.0263 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Creatinine: Change from baseline to Week 32 | 0.054 milligrams per deciliter (mg/dL) | Standard Deviation 0.3404 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Direct Bilirubin: Change from baseline to Week 32 | 0.018 milligrams per deciliter (mg/dL) | Standard Deviation 0.03 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Bilirubin: Change from baseline to Week 32 | 0.105 milligrams per deciliter (mg/dL) | Standard Deviation 0.1576 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Calcium: Change from baseline to Week 32 | 0.16 milligrams per deciliter (mg/dL) | Standard Deviation 0.524 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Glucose: Change from baseline to Week 32 | 9.2 milligrams per deciliter (mg/dL) | Standard Deviation 64.86 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Phosphate: Change from baseline to Week 32 | 0.02 milligrams per deciliter (mg/dL) | Standard Deviation 0.62 |
| Ziltivekimab 15 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Urea Nitrogen: Change from baseline to Week 32 | 1.6 milligrams per deciliter (mg/dL) | Standard Deviation 7.97 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Calcium: Change from baseline to Week 32 | 0.11 milligrams per deciliter (mg/dL) | Standard Deviation 0.405 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Urea Nitrogen: Change from baseline to Week 32 | 5.6 milligrams per deciliter (mg/dL) | Standard Deviation 13.89 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Phosphate: Change from baseline to Week 32 | 0.21 milligrams per deciliter (mg/dL) | Standard Deviation 0.641 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Bilirubin: Change from baseline to Week 32 | 0.065 milligrams per deciliter (mg/dL) | Standard Deviation 0.1812 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Direct Bilirubin: Change from baseline to Week 32 | 0.009 milligrams per deciliter (mg/dL) | Standard Deviation 0.0367 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Glucose: Change from baseline to Week 32 | 1.7 milligrams per deciliter (mg/dL) | Standard Deviation 48.43 |
| Ziltivekimab 30 mg | Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen | Creatinine: Change from baseline to Week 32 | 0.141 milligrams per deciliter (mg/dL) | Standard Deviation 0.4618 |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data and 'Number Analyzed' = number of participants with available data for each category.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Normal | 14 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Unknown | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, not clinically significant | 36 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, clinically significant | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Indeterminate | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Indeterminate | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Normal | 21 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, not clinically significant | 44 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Not evaluable | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Not evaluable | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Baseline (week-1) | Unknown | 0 Participants |
| Placebo | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, not clinically significant | 38 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Normal | 27 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Indeterminate | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Normal | 22 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, not clinically significant | 32 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Unknown | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Not evaluable | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Indeterminate | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Unknown | 0 Participants |
| Ziltivekimab 7.5 mg | Change in Electrocardiogram (ECG) | Week 24 | Not evaluable | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, not clinically significant | 35 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, not clinically significant | 40 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Indeterminate | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Normal | 25 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Not evaluable | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Unknown | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Indeterminate | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Normal | 18 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Not evaluable | 0 Participants |
| Ziltivekimab 15 mg | Change in Electrocardiogram (ECG) | Week 24 | Unknown | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Unknown | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Not evaluable | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Normal | 18 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Normal | 18 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Indeterminate | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Unknown | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Not evaluable | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, not clinically significant | 34 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Abnormal, clinically significant | 0 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Baseline (week-1) | Abnormal, not clinically significant | 46 Participants |
| Ziltivekimab 30 mg | Change in Electrocardiogram (ECG) | Week 24 | Indeterminate | 0 Participants |
Secondary
Change in Heart Rate
Change from baseline in heart rate at Week 32 are presented.
Time frame: Baseline (week 1), week 32
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Heart Rate | 2.8 Beats per minute (beats/min) | Standard Deviation 9.7 |
| Ziltivekimab 7.5 mg | Change in Heart Rate | 1.5 Beats per minute (beats/min) | Standard Deviation 10.18 |
| Ziltivekimab 15 mg | Change in Heart Rate | -0.6 Beats per minute (beats/min) | Standard Deviation 8.93 |
| Ziltivekimab 30 mg | Change in Heart Rate | 1.2 Beats per minute (beats/min) | Standard Deviation 11.56 |
Secondary
Change in Respiratory Rate
Change from baseline in respiratory rate at week 32 are presented.
Time frame: Baseline (week 1), week 32
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Respiratory Rate | 0.4 Breaths per minute (breaths/min) | Standard Deviation 2.24 |
| Ziltivekimab 7.5 mg | Change in Respiratory Rate | 0.2 Breaths per minute (breaths/min) | Standard Deviation 2.18 |
| Ziltivekimab 15 mg | Change in Respiratory Rate | -0.7 Breaths per minute (breaths/min) | Standard Deviation 2.36 |
| Ziltivekimab 30 mg | Change in Respiratory Rate | -0.5 Breaths per minute (breaths/min) | Standard Deviation 1.62 |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Systolic Blood Pressure (SBP) | 4.8 Millimeters of mercury (mmHg) | Standard Deviation 15.94 |
| Ziltivekimab 7.5 mg | Change in Systolic Blood Pressure (SBP) | 4.9 Millimeters of mercury (mmHg) | Standard Deviation 16.31 |
| Ziltivekimab 15 mg | Change in Systolic Blood Pressure (SBP) | 0.6 Millimeters of mercury (mmHg) | Standard Deviation 18.89 |
| Ziltivekimab 30 mg | Change in Systolic Blood Pressure (SBP) | 1.2 Millimeters of mercury (mmHg) | Standard Deviation 14.71 |
Secondary
Change in Temperature
Change from baseline in temperature at week 32 are presented.
Time frame: Baseline (week 1), week 32
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change in Temperature | 0.03 Degree Celsius (°C) | Standard Deviation 0.456 |
| Ziltivekimab 7.5 mg | Change in Temperature | -0.01 Degree Celsius (°C) | Standard Deviation 0.43 |
| Ziltivekimab 15 mg | Change in Temperature | -1.13 Degree Celsius (°C) | Standard Deviation 8.366 |
| Ziltivekimab 30 mg | Change in Temperature | -0.02 Degree Celsius (°C) | Standard Deviation 0.615 |
Secondary
Follicle Stimulating Hormone (FSH) Levels
FSH levels at baseline (week -1) are presented.
Time frame: Baseline (week -1)
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Follicle Stimulating Hormone (FSH) Levels | 57.45 International units per liter (IU/L) | Standard Deviation 20.496 |
| Ziltivekimab 7.5 mg | Follicle Stimulating Hormone (FSH) Levels | 72.70 International units per liter (IU/L) | Standard Deviation 36.519 |
| Ziltivekimab 15 mg | Follicle Stimulating Hormone (FSH) Levels | 77.49 International units per liter (IU/L) | Standard Deviation 33.827 |
| Ziltivekimab 30 mg | Follicle Stimulating Hormone (FSH) Levels | 58.79 International units per liter (IU/L) | Standard Deviation 48.167 |
Secondary
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
Population: Analysis population included all randomized participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Anti-drug Antibodies (ADAs) | 0 Participants |
| Ziltivekimab 7.5 mg | Number of Participants With Anti-drug Antibodies (ADAs) | 4 Participants |
| Ziltivekimab 15 mg | Number of Participants With Anti-drug Antibodies (ADAs) | 5 Participants |
| Ziltivekimab 30 mg | Number of Participants With Anti-drug Antibodies (ADAs) | 7 Participants |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Serious infection | 4.6 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Severe injection-related reaction | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Hypersensitivity reaction during IP administration | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, moderate with evidence of concurrent TIMI major bleeding | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Gastrointestinal perforations | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Anaphylaxis | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, severe | 0.0 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Malignancy | 1.5 Percentage of participants |
| Placebo | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe with evidence of concurrent infection | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Hypersensitivity reaction during IP administration | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe with evidence of concurrent infection | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Anaphylaxis | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Gastrointestinal perforations | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Serious infection | 10.8 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Severe injection-related reaction | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, moderate with evidence of concurrent TIMI major bleeding | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Malignancy | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Gastrointestinal perforations | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Hypersensitivity reaction during IP administration | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Serious infection | 4.5 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Severe injection-related reaction | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, moderate with evidence of concurrent TIMI major bleeding | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Anaphylaxis | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe with evidence of concurrent infection | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Malignancy | 1.5 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Serious infection | 3.1 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Neutropenia, severe with evidence of concurrent infection | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Severe injection-related reaction | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, moderate with evidence of concurrent TIMI major bleeding | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Thrombocytopenia, severe | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Malignancy | 1.5 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Anaphylaxis | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Gastrointestinal perforations | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI) | Hypersensitivity reaction during IP administration | 0.0 Percentage of participants |
Secondary
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.
Time frame: From week 0 to week 32
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events | 0.0 Percentage of participants |
| Ziltivekimab 15 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events | 0.0 Percentage of participants |
Secondary
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
Population: The safety analysis population included all randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 | TEAEs | 69.2 Percentage of participants |
| Placebo | 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 | Severe non-hematologic AEs | 10.8 Percentage of participants |
| Placebo | 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 | AEs leading to study drug discontinuation | 4.6 Percentage of participants |
| Placebo | 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 | Severe hematologic AEs | 1.5 Percentage of participants |
| Placebo | 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 | TESAEs | 15.4 Percentage of participants |
| Ziltivekimab 7.5 mg | 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 | Severe hematologic AEs | 0.0 Percentage of participants |
| Ziltivekimab 7.5 mg | 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 | Severe non-hematologic AEs | 18.5 Percentage of participants |
| Ziltivekimab 7.5 mg | 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 | AEs leading to study drug discontinuation | 6.2 Percentage of participants |
| Ziltivekimab 7.5 mg | 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 | TESAEs | 20.0 Percentage of participants |
| Ziltivekimab 7.5 mg | 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 | TEAEs | 66.2 Percentage of participants |
| Ziltivekimab 15 mg | 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 | Severe hematologic AEs | 1.5 Percentage of participants |
| Ziltivekimab 15 mg | 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 | TEAEs | 66.7 Percentage of participants |
| Ziltivekimab 15 mg | 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 | TESAEs | 13.6 Percentage of participants |
| Ziltivekimab 15 mg | 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 | Severe non-hematologic AEs | 9.1 Percentage of participants |
| Ziltivekimab 15 mg | 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 | AEs leading to study drug discontinuation | 7.6 Percentage of participants |
| Ziltivekimab 30 mg | 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 | Severe non-hematologic AEs | 12.3 Percentage of participants |
| Ziltivekimab 30 mg | 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 | TESAEs | 12.3 Percentage of participants |
| Ziltivekimab 30 mg | 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 | TEAEs | 72.3 Percentage of participants |
| Ziltivekimab 30 mg | 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 | Severe hematologic AEs | 0.0 Percentage of participants |
| Ziltivekimab 30 mg | 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 | AEs leading to study drug discontinuation | 4.6 Percentage of participants |
Secondary
Percent Change From Baseline in Fibrinogen
Percent change from baseline in fibrinogen at week 13 are presented.
Time frame: Baseline (day 1), week 13
Population: ITT analysis population included all randomized participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Fibrinogen | -1.62 Percent change |
| Ziltivekimab 7.5 mg | Percent Change From Baseline in Fibrinogen | -25.20 Percent change |
| Ziltivekimab 15 mg | Percent Change From Baseline in Fibrinogen | -24.69 Percent change |
| Ziltivekimab 30 mg | Percent Change From Baseline in Fibrinogen | -37.17 Percent change |
Secondary
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
Population: ITT analysis population included all randomized participants. 'Overall Number of Participants Analyzed' = participants with available data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Percent Change From Baseline in Serum Amyloid A (SAA) | 1.82 Percent change |
| Ziltivekimab 7.5 mg | Percent Change From Baseline in Serum Amyloid A (SAA) | -40.24 Percent change |
| Ziltivekimab 15 mg | Percent Change From Baseline in Serum Amyloid A (SAA) | -49.80 Percent change |
| Ziltivekimab 30 mg | Percent Change From Baseline in Serum Amyloid A (SAA) | -42.45 Percent change |