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 (NN6018-4776)

JRCT ID: jRCT2031200216

Registered date:25/11/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Chronic kidney disease
• Date of first enrollment: 22/10/2020
• Target sample size: 36
• Study type: Interventional

Intervention(s)

-Ziltivekimab at 2 dose levels (15 mg or 30 mg) compared to placebo
-The study will consist of 3 periods: a Screening Period, a Treatment Period, and a Safety Follow-Up Period.
-There are some rules regarding Excluded and Restricted Medications and/or Procedures
-Implementation of blood sampling tests, etc. specified in the protocol.
-Total study duration is approximately 6 months.

Outcome(s)

• Primary Outcome: The difference in the percent change in 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) between each active group and placebo.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

After signing an informed consent form (ICF) approved by the Institutional Review Board or Independent Ethics Committee, in order to be eligible, potential patients must meet all of the following criteria:
1. Age >=20 years at the time of signing the ICF;
2. Stage 3 to 5 NDD-CKD, ie, estimated glomerular filtration rate >10 and <60 mL/min/1.73 m2 using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine equation;
3. Serum hs-CRP level >_2.0 mg/L measured during the Screening Period;
Note: Targeting patients with a history of advanced stage chronic kidney disease (CKD),
atherosclerotic cardiovascular disease, anemia, diabetic retinopathy, obesity, or elevated body mass index (BMI), and diabetes for Screening will help increase the chances of identifying patients with hs-CRP >=2.0 mg/L;
4. The patient agrees to comply with the contraception and reproduction restrictions of the study as follows:
a. Women of childbearing potential must be using a method of contraception that is highly effective (ie, <1% failure rate) for at least 3 months following the last dose of study drug;
b. 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, >40 mIU/mL) at Screening;
c. Women of childbearing potential must have a documented negative serum pregnancy test result at Screening; and
d. 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
5. The patient must be willing and able to provide informed consent and abide all study requirements and restrictions.

Exclude criteria

1. Absolute neutrophil count <2.0 x 10 x9/L during Screening;
2. Platelet count <120 x 10 x 9/L during Screening;
3. Spot urine protein-creatinine ratio >4000 mg/g (4.0 g/g) during Screening;
4. Alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal during Screening;
5. 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;
6. Evidence of human immunodeficiency virus (HIV)-1 or HIV-2 infection by serology measured during Screening;
7. Hepatitis B or C by serology (eg, hepatitis B surface antigen or hepatitis C antibody positive) measured during Screening;
8. Expected to require blood transfusion within 12 weeks post-randomization;
9. Thromboembolic event within 12 weeks prior to randomization;
10. Clinical evidence or suspicion of active infection;
11. History of peptic ulcer disease or gastrointestinal ulceration in the 12 months prior to randomization;
12. History of active diverticulitis in the 12 months prior to randomization;
13. History of inflammatory bowel disease that has been clinically active during the 12 months prior to randomization;
14. Uncontrolled hypertension (defined as an average systolic blood pressure >160 mmHg or an average diastolic blood pressure >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;
15. Planned coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) or any other major surgical procedure during the time frame of the study;
16. Major cardiac surgical, non-cardiac surgical, or major endoscopic procedure within the past 6 months prior to randomization;
17. Prior gastric bypass surgery;
18. History of New York Heart Association Class IV congestive heart failure within 12 weeks
19. 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;
20. History of bone marrow or solid organ transplant or anticipated to receive an organ transplant during the time frame of the study;
21. Known allergy to the study drug or any of its ingredients;
22. Received an investigational drug within 30 days prior to Screening;
23. Received a live vaccine product within 14 days of study drug administration or expect to receive live vaccine during the Treatment Period;
24. Expected to receive any investigational drug or any of the exclusionary drugs during the Treatment Period or Safety Follow-Up Period;
25. 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;
26. 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;
27. Requirement of an indwelling catheter of any type;
28. Currently breastfeeding; or
29. 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.

Related Information

• Primary Sponsor: Kanmuri Kazuhiro
• Secondary ID(s): NCT04626505