Chronic Kidney DiseasePhase 2RESCUE-2NCT04626505
Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition in Japan.
A Phase 2 study testing Ziltivekimab in people with Chronic Kidney Disease and Inflammation, run by Novo Nordisk A/S at 1 site in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Chronic Kidney Disease, Inflammation, Cardiovascular Risk
- What is being tested?
- Ziltivekimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteJapan
- Study dates
- 22 Oct 2020to 28 Sep 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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;
- 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;
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- Women of childbearing potential must have a documented negative serum pregnancy test result at screening; and
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody-Mediated Interleukin-6 Inhibition in Japan
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.
- Conditions
- Chronic Kidney Disease, Inflammation, Cardiovascular Risk
- Being tested
- Ziltivekimab, Placebo (ziltivekimab)
- Medical subject headings
- Renal Insufficiency, Chronic, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZiltivekimabDrug
Administered subcutaneously (s.c., under skin) once every 4 weeks for 12 weeks
Placebo (ziltivekimab)Drug
Administered s.c. once every 4 weeks for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ziltivekimab 15 mg | Experimental | Participants will receive ziltivekimab 15 mg for 12 weeks. Receives: Drug: Ziltivekimab |
| Ziltivekimab 30 mg | Experimental | Participants will receive ziltivekimab 30 mg for 12 weeks. Receives: Drug: Ziltivekimab |
| Placebo (ziltivekimab) | Placebo comparator | Participants will receive placebo (ziltivekimab) for 12 weeks. Receives: Drug: Placebo (ziltivekimab) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
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.
Measured: Baseline (day 1), end of treatment (average of week 10 and week 12)
Secondary outcomes (26)
Number of Treatment-emergent Adverse Events (TEAEs)
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.
Measured: From randomization (Day 1) to week 20
Number of Serious Adverse Events (SAEs)
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.
Measured: From randomization (Day 1) to week 20
Number of Participants With Vital Signs Parameters Exceeding Pre-defined Criteria
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.
Measured: From randomization (Day 1) to week 20
Change in Electrocardiogram (ECG)
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.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase (LDH) and Lipase Pancreatic
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.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Bicarbonate, Chloride, Potassium and Sodium
Change from baseline (Day 1) to Week 20 in bicarbonate, chloride, potassium and sodium is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Bilirubin, Calcium, Creatinine, Direct Bilirubin, Glucose, Phosphate, Urate, Urea Nitrogen
Change from baseline (Day 1) to week 20 in bilirubin, calcium, creatinine, direct bilirubin, glucose, phosphate, urate and urea nitrogen is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Glomerular Filtration Rate
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.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Protein
Change from baseline (Day 1) to week 20 in protein is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Eosinophils, Leukocyctes, Lymphocytes, Monocytes, Neutrophils and Platelets
Change from baseline (Day 1) to week 20 in eosinophils, leukocyctes, lymphocytes, monocytes, neutrophils and platelets is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Eosinophil/Leukocytes
Change from baseline (Day 1) to week 20 in eosinophil/leukocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Erythrocyte Mean Corpuscular Volume
Change from baseline (Day 1) to week 20 in erythrocyte mean corpuscular volume is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Erythrocytes
Change from baseline (Day 1) to week 20 in erythrocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Erythrocyte Distribution Width
Change from baseline (Day 1) to week 20 in erythrocyte distribution width (ery. distribution width) is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Hematocrit
Change from baseline (Day 1) to week 20 in hematocrit is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Lymphocytes/Leukocytes
Change from baseline (Day 1) to week 20 in lymphocytes/leukocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Monocytes/Leukocytes
Change from baseline (Day 1) to week 20 in monocytes/leukocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Neutrophils/Leukocytes
Change from baseline (Day 1) to week 20 in neutrophils/leukocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Reticulocytes/Erythrocytes
Change from baseline (Day 1) to week 20 in reticulocytes/erythrocytes is presented.
Measured: Baseline (Day 1), Week 20
Change From Baseline in Protein Creatinine Ratio
Change from baseline (Day 1) to week 12 in protein creatinine ratio is presented.
Measured: Baseline (Day 1), Week 12
Change From Baseline in Specific Gravity of Urine
Change from baseline (Day 1) to week 12 in specific gravity of urine is presented.
Measured: Baseline (Day 1), Week 12
Change From Baseline in Spot Urine Albumin, Spot Urine Creatinine, Spot Urine Protein and Urobilinogen
Change from baseline (Day 1) to week 12 in spot urine albumin, spot urine creatinine, spot urine protein and urobilinogen is presented.
Measured: Baseline (Day 1), Week 12
Change From Baseline in Urine pH
Change from baseline (Day 1) to week 12 in urine pH is presented.
Measured: Baseline (Day 1), Week 12
Percentage of Participants With Adverse Events (AEs) Leading to Discontinuation of Study Drug
Percentage of participants with AEs leading to discontinuation of study drug is presented.
Measured: From randomization (Day 1) to week 20
Number of Treatment Emergent Adverse Events of Special Interest (AESIs)
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.
Measured: From randomization (Day 1) to week 20
Number of Participants With Antidrug Antibodies (ADAs) to Ziltivekimab
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.
Measured: From randomization (Day 1) to week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2020
- Study start22 Oct 2020
- Primary completion3 Aug 2021
- Study completion28 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Corvidia Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04626505
- Sponsor's protocol ID
- NN6018-4776
- Other IDs
- U1111-1260-3695, jRCT2031200216
- Acronym
- RESCUE-2
- Status last verified
- May 2026
- First submitted
- 10 Nov 2020
- Last updated
- 6 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
Wada Y, Jensen C, Meyer ASP, Zonoozi AAM, Honda H. Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial. J Cardiol. 2023 Oct;82(4):279-285. doi: 10.1016/j.jjcc.2023.05.006. Epub 2023 May 19.
PubMed 37211246