Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition
ID: NCT03926117
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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.
human IgG1k anti-human IL-6 monoclonal antibody
Treatment Arms Description
Matching placebo
- 18 years of age
- Stage 3-5 CKD
- hs-CRP \> 2.0 mg/L
- Comply with contraception
- Low neutrophil count
- Low platelet count
- Spot urine protein to creatinine ration \> 4000 mg/g
- ALT/AST \>2.5x ULN
- TSAT \< 10%
- Positive TB test
- Evidence of HIV, hepatitis B
- Blind or illiterate
- Expected to require blood transfusion
- Thromboembolic event within 12-weeks
- Evidence of active infection
- Peptic ulcer disease, diverticulitis, inflammatory bowel disease
- Uncontrolled hypertension
- Planned coronary revascularization
- Major cardiac surgery, CHF
- Active malignancy, bone marrow or organ transplant
- Allergy to study drug
- Treatment with investigational drug, treatment with HIF stabilizer or ESA
- Use of immunosuppressive drugs, systemic antibiotics
- Breastfeeding, any other significant medical history
Primary Outcome Measures
- Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels — Time Frame: 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.
View Secondary Outcome Measures (17)
- Percent Change From Baseline in Serum Amyloid A (SAA) — Time Frame: Baseline (average of the values at week -1 and day 1), week 13
Percent change from baseline in SAA at week 13 are presented.
- Percent Change From Baseline in Fibrinogen — Time Frame: 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 — Time Frame: 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 — Time Frame: 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) — Time Frame: 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) — Time Frame: Baseline (week 1), week 32
Change from baseline in systolic blood pressure at week 32 are presented.
- Change in Diastolic Blood Pressure (DBP) — Time Frame: Baseline (week 1), week 32
Change from baseline in diastolic blood pressure at week 32 are presented.
- Change in Respiratory Rate — Time Frame: Baseline (week 1), week 32
Change from baseline in respiratory rate at week 32 are presented.
- Change in Body Mass Index (BMI) — Time Frame: Baseline (week 1), week 24
Change from baseline in BMI at week 24 are presented.
- Change in Heart Rate — Time Frame: Baseline (week 1), week 32
Change from baseline in heart rate at Week 32 are presented.
This trial is recruiting at 49 study facilities worldwide. Click below to see if there is a clinic or hospital in your area:
Show All 49 Facilities & Contact Sites
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- Kreiner FF, Kraaijenhof JM, von Herrath M, Hovingh GKK, von Scholten BJ. Interleukin 6 in diabetes, chronic kidney disease, and cardiovascular disease: mechanisms and therapeutic perspectives. Expert Rev Clin Immunol. 2022 Apr;18(4):377-389. doi: 10.1080/1744666X.2022.2045952. Epub 2022 Mar 1.PubMed ↗
- Hu S, Lee K, He JC, Fan Y. Current Landscape and Emerging Therapeutic Targets in Diabetic Kidney Disease. Clin J Am Soc Nephrol. 2026 Mar 10. doi: 10.2215/CJN.0000001053. Online ahead of print.PubMed ↗
- Aherrahrou R, Reinberger T, Hashmi S, Erdmann J. GWAS breakthroughs: mapping the journey from one locus to 393 significant coronary artery disease associations. Cardiovasc Res. 2024 Nov 5;120(13):1508-1530. doi: 10.1093/cvr/cvae161.PubMed ↗
- Pergola PE, Davidson M, Jensen C, Mohseni Zonoozi AA, Raj DS, Andreas Schytz P, Tuttle KR, Perkovic V. Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized Trial (RESCUE). J Am Soc Nephrol. 2024 Jan 1;35(1):74-84. doi: 10.1681/ASN.0000000000000245. Epub 2023 Dec 13.PubMed ↗
- Ridker PM, Devalaraja M, Baeres FMM, Engelmann MDM, Hovingh GK, Ivkovic M, Lo L, Kling D, Pergola P, Raj D, Libby P, Davidson M; RESCUE Investigators. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021 May 29;397(10289):2060-2069. doi: 10.1016/S0140-6736(21)00520-1. Epub 2021 May 17.PubMed ↗
View Official Medical/Scientific Title
A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition