Cardiovascular Risk, Chronic Kidney Disease, Inflammation
Conditions
Brief summary
The purpose of this research study is to compare the safety and effectiveness of 2 different doses of a study drug called ziltivekimab to placebo (an inactive substance) in reducing inflammation and improving some of the bad effects of inflammation on heart disease. Participants will be randomly (by chance) assigned to receive either ziltivekimab or placebo. The chance that participants will be assigned into one of the three study arms of ziltivekimab (either 15 mg or 30 mg) or placebo is the same (approximately 33%). This is a double-blind study, which means neither participants nor the study doctor will know which group the participants are in. In case of an emergency, however, the study doctor can get this information. The study drug will be injected under the skin once every 4 weeks. In this study participants will receive 3 injections of study drug. The total study duration for each participant will be approximately 6 months.
Interventions
DRUGZiltivekimab
Administered subcutaneously (s.c., under skin) once every 4 weeks for 12 weeks
Administered s.c. once every 4 weeks for 12 weeks
Sponsors
Novo Nordisk A/S
Sponsor: Corvidia Therapeutics Inc, a subsidiary of Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age equal to or above 20 years at the time of signing the Informed Consent Form * Stage 3 to 5 non-dialysis-dependent chronic kidney disease (NDD-CKD), ie, estimated glomerular filtration rate above 10 and below 60 mL/min/1.73 m\^2 using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation * Serum hs-CRP level equal to or above 2.0 mg/L measured during the screening period. Note: Targeting patients with a history of advanced stage CKD, atherosclerotic cardiovascular disease, anemia, diabetic retinopathy, obesity, or elevated BMI, and diabetes for screening will help increase the chances of identifying patients with hs-CRP equal to or above2.0 mg/L 4. The patient agrees to comply with * The patient agrees to comply with the contraception and reproduction restrictions of the study as follows: 1. Women of childbearing potential must be using a method of contraception that is "highly effective" (ie, less than 1% failure rate) for at least 3 months following the last dose of study drug; 2. Postmenopausal women must have had no menstrual bleeding for at least 1 year before initial dosing and either be over the age of 60 years or have an elevated plasma follicle stimulating hormone level (ie, above 40 mIU/mL) at screening; 3. Women of childbearing potential must have a documented negative serum pregnancy test result at screening; and 4. All male patients, from the day of dosing until the final study visit, unless surgically sterile, must be willing to use a condom with a partner (male patients with partners of childbearing potential must be willing to use 2 effective methods of birth control, 1 should be condom with spermicide) to prevent pregnancy and drug exposure of a partner, and refrain from donating sperm or fathering a child; and * The patient must be willing and able to provide informed consent and abide all study requirements and restrictions.
Exclusion criteria
Patients who meet any of the following criteria will be excluded from participation in the study: Laboratory values * Absolute neutrophil count below 2.0 × 10\^9/L during screening; * Platelet count below 120 × 10\^9/L during screening; * Spot urine protein-creatinine ratio above 4000 mg/g (4.0 g/g) during screening; * Alanine aminotransferase or aspartate aminotransferase above 2.5 × upper limit of normal during screening; * Positive testing for tuberculosis during screening. blood testing (eg, QuantiFERON) is preferred, but a purified protein derivative (PPD) skin test read within 48 to 72 hours by a qualified healthcare professional may also be performed. If a patient is PPD positive but QuantiFERON negative, the patient is eligible; * Evidence of human immunodeficiency virus (HIV)-1 or HIV-2 infection by serology measured during screening; * Hepatitis B or C by serology (eg, hepatitis B surface antigen or hepatitis C antibody positive) measured during screening; Medical conditions or diseases * Expected to require blood transfusion within 12 weeks post-randomization; * Thromboembolic event within 12 weeks prior to randomization; * Clinical evidence or suspicion of active infection; * History of peptic ulcer disease or gastrointestinal ulceration in the 12 months prior to randomization; * History of active diverticulitis in the 12 months prior to randomization; * History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomization; * Uncontrolled hypertension (defined as an average systolic blood pressure above 160 mmHg or an average diastolic blood pressure above 100 mmHg) during screening. Patients may be re-evaluated within 2 weeks, at the discretion of the Principal Investigator, for this criterion if antihypertensive therapy has been started or increased as a result of initial screening blood pressure being above these limits; * Planned coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or any other major surgical procedure during the time frame of the study; * Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure within the past 6 months prior to randomization; * Prior gastric bypass surgery; * History of New York Heart Association (NYHA) Class IV congestive heart failure within 12 weeks prior to randomization; * Diagnosis of malignancy within 1 year prior to randomization with the exception of successfully treated nonmetastatic basal cell or squamous cell carcinomas of the skin and/or local carcinoma in situ of the cervix; * History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the time frame of the study; * Known allergy to the study drug or any of its ingredients; Prior or current medications * Received an investigational drug within 30 days prior to screening; * Received a live vaccine product within 14 days of study drug administration or expect to receive live vaccine during the treatment period; * Expected to receive any investigational drug or any of the exclusionary drugs during the treatment period or safety follow-Up period; * Chronic use of systemic immunosuppressive drugs during the screening period or anticipated use of such drugs any time during the study. Note: Use of otic, ophthalmic, inhaled, and topical corticosteroids or local corticosteroid injections are not exclusionary. Oral prednisone up to 5 mg per day (or equivalent) is permitted if the dose has been stable for at least 4 weeks prior to Screening and no dose changes are planned during study participation. Short-term use of oral steroids for treatment of rash or asthma exacerbation is allowed; * Use of systemic antibiotics, systemic antivirals, or systemic antifungals during the screening period. Note: "Systemic" is defined as oral or intravenous drugs that are absorbed into the circulation; * Requirement of an indwelling catheter of any type; 28. Use of hypoxia-inducible factor (HIF) stabilizers or erythropoiesis-stimulating agents (ESA) within 6 weeks of randomization or during the treatment period; General exclusions * Currently breastfeeding; or * Any condition that could interfere with, or for which the treatment might interfere with, the conduct of the study or interpretation of the study results, or that would in the opinion of the Investigator increase the risk of participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in High-sensitivity C-reactive Protein (Hs-CRP) Levels From Baseline (Average of All Hs-CRP Values Prior to the Administration of Study Drug) to the End of Treatment (Average of Week 10 and Week 12) | Baseline (day 1), end of treatment (average of week 10 and week 12) | Percent change in hs-CRP levels from baseline (average of the hs-CRP value prior to the administration of study drug) to the end of treatment (average of Week 10 and Week 12) is presented. Baseline was defined as the average of all hs-CRP values prior to the first administration of study drug at day 1 and end of treatment was defined as the average of hs-CRP values at week 10 and week 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment-emergent Adverse Events (TEAEs) | From randomization (Day 1) to week 20 | An adverse event (AE) was any undesirable event or any untoward medical occurrence that occurred in a participant during the course of the study or the protocol-defined time after study termination, whether or not that event was considered study drug-related. A TEAE was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of the safety follow-up period (week 20). Number of TEAEs from randomization (day 1) to week 20 are presented. |
| Number of Serious Adverse Events (SAEs) | From randomization (Day 1) to week 20 | An AE was any undesirable event or any untoward medical occurrence that occurred in a participant during the course of the study or the protocol-defined time after study termination, whether or not that event was considered study drug-related. An 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. ). Number of SAEs from randomization (day 1) to week 20 are presented. |
| Number of Participants With Vital Signs Parameters Exceeding Pre-defined Criteria | From randomization (Day 1) to week 20 | Number of participants with vital signs parameters (including systolic blood pressure, heart rate and respiratory rate) exceeding pre-defined criteria are presented. The pre-defined criteria were: 1) systolic blood pressure: greater than (\>25) millimeters of mercury (mmHg) increase or decrease from baseline and \>160 mmHg; 2) heart rate: \>100 beats per minute; 3)respiratory rate: \>24 breaths per minute. |
| Change in Electrocardiogram (ECG) | Baseline (Day 1), Week 20 | The ECG was assessed by the investigator at baseline (Day 1) and week 20 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 20 are presented. |
| Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase (LDH) and Lipase Pancreatic | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, creatine kinase, gamma glutamyl transferase, LDH and lipase pancreatic is presented. |
| Change From Baseline in Bicarbonate, Chloride, Potassium and Sodium | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to Week 20 in bicarbonate, chloride, potassium and sodium is presented. |
| Change From Baseline in Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Phosphate, Urate, Urea Nitrogen | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in bilirubin, calcium, creatinine, direct bilirubin, glucose, phosphate, urate and urea nitrogen is presented. |
| Change From Baseline in Glomerular Filtration Rate | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in glomerular filtration rate is presented. Glomerular filtration rate was calculated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)creatinine equation. |
| Change From Baseline in Protein | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in protein is presented. |
| Change From Baseline in Eosinophils, Leukocyctes, Lymphocytes, Monocytes, Neutrophils and Platelets | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in eosinophils, leukocyctes, lymphocytes, monocytes, neutrophils and platelets is presented. |
| Change From Baseline in Eosinophil/Leukocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in eosinophil/leukocytes is presented. |
| Change From Baseline in Erythrocyte Mean Corpuscular Volume | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in erythrocyte mean corpuscular volume is presented. |
| Change From Baseline in Erythrocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in erythrocytes is presented. |
| Change From Baseline in Erythrocyte Distribution Width | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in erythrocyte distribution width (ery. distribution width) is presented. |
| Change From Baseline in Hematocrit | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in hematocrit is presented. |
| Change From Baseline in Lymphocytes/Leukocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in lymphocytes/leukocytes is presented. |
| Change From Baseline in Monocytes/Leukocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in monocytes/leukocytes is presented. |
| Change From Baseline in Neutrophils/Leukocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in neutrophils/leukocytes is presented. |
| Change From Baseline in Reticulocytes/Erythrocytes | Baseline (Day 1), Week 20 | Change from baseline (Day 1) to week 20 in reticulocytes/erythrocytes is presented. |
| Change From Baseline in Protein Creatinine Ratio | Baseline (Day 1), Week 12 | Change from baseline (Day 1) to week 12 in protein creatinine ratio is presented. |
| Change From Baseline in Specific Gravity of Urine | Baseline (Day 1), Week 12 | Change from baseline (Day 1) to week 12 in specific gravity of urine is presented. |
| Change From Baseline in Spot Urine Albumin, Spot Urine Creatinine, Spot Urine Protein and Urobilinogen | Baseline (Day 1), Week 12 | Change from baseline (Day 1) to week 12 in spot urine albumin, spot urine creatinine, spot urine protein and urobilinogen is presented. |
| Change From Baseline in Urine pH | Baseline (Day 1), Week 12 | Change from baseline (Day 1) to week 12 in urine pH is presented. |
| Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of Study Drug | From randomization (Day 1) to week 20 | Percentage of participants with AEs leading to discontinuation of study drug is presented. |
| Number of Treatment Emergent Adverse Events of Special Interest (AESIs) | From randomization (Day 1) to week 20 | AESIs included serious infection, Common Terminology Criteria for Adverse Events (CTCAE) Grade greater than or equal to (\>=) 3 injection-related reactions, gastrointestinal perforations, CTCAE Grade \>=3 anaphylaxis that occurred at any time, even if considered unrelated to the study drug, neutrophil less than (\<) 500/mm\^3 (CTCAE Grade 4) or neutrophil \<1000/mm\^3 (CTCAE Grade 3) with evidence of concurrent infection, thrombocytopenia (platelet count \<50,000/mm\^3 \[CTCAE Grade 3\]) or platelet count \<75,000/mm\^3 (CTCAE Grade 2) with evidence of concurrent major bleeding and malignancies. Number of treatment emergent adverse events of special interest (AESIs) is presented. |
| Number of Participants With Antidrug Antibodies (ADAs) to Ziltivekimab | From randomization (Day 1) to week 20 | Number of participants with ADAs to Ziltivekimab is presented. Data presented is partcipants who had at least 1 positive antibody sample (treatment-boosted or treatment-induced) at any time after their first Ziltivekimab administration. |
Countries
Japan
Participant flow
Recruitment details
The trial was conducted in Japan and included 12 sites that were initiated, 11 sites that screened study participants, and 10 sites that enrolled study participants.
Pre-assignment details
Participants were randomized 1:1:1 to ziltivekimab 15 milligrams (mg), ziltivekimab 30 mg, or placebo groups for a 12-week treatment period. Participants were followed for safety from week 12 to week 20.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.7 Years STANDARD_DEVIATION 12.44 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 | 0 / 12 |
| other Total, other adverse events | 7 / 12 | 10 / 11 | 7 / 12 |
| serious Total, serious adverse events | 2 / 12 | 2 / 11 | 0 / 12 |
Outcome results
None listed