NCT04626505 - Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition in Japan. | Crick

Eligibility

Sex: ALLMin age: 20 Years

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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.

Outcomes

Primary Outcomes

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.

Time frame: Baseline (day 1), end of treatment (average of week 10 and week 12)

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.