Clinical trial NCT03926117: Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Diseases
Inflammation
Keywords: IL-6
CRP
Chronic Kidney Disease
Cardiovascular Disease
Inflammation
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2019-04-24
Enrollment: 264
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 18 years of age
* Stage 3-5 CKD
* hs-CRP \> 2.0 mg/L
* Comply with contraception

Exclusion Criteria:

* 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 outcomes:
measure: Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels
timeFrame: Baseline (average of the hs-CRP value prior to randomization and day 1), week 13
Secondary outcomes:
measure: Percent Change From Baseline in Serum Amyloid A (SAA)
timeFrame: Baseline (average of the values at week -1 and day 1), week 13
measure: Percent Change From Baseline in Fibrinogen
timeFrame: Baseline (day 1), week 13
measure: 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
timeFrame: From week 0 to week 32
measure: Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events
timeFrame: From week 0 to week 32
measure: Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI)
timeFrame: From week 0 to week 32
measure: Change in Systolic Blood Pressure (SBP)
timeFrame: Baseline (week 1), week 32
measure: Change in Diastolic Blood Pressure (DBP)
timeFrame: Baseline (week 1), week 32
measure: Change in Respiratory Rate
timeFrame: Baseline (week 1), week 32
measure: Change in Body Mass Index (BMI)
timeFrame: Baseline (week 1), week 24
measure: Change in Heart Rate
timeFrame: Baseline (week 1), week 32
measure: Change in Temperature
timeFrame: Baseline (week 1), week 32
measure: Change in Electrocardiogram (ECG)
timeFrame: Baseline (week -1), Week 24
measure: Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels
timeFrame: Baseline (week 1), week 32
measure: Change in Bicarbonate, Chloride, Potassium, Sodium
timeFrame: Baseline (week 1), week 32
measure: Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen
timeFrame: Baseline (week 1), week 32
measure: Follicle Stimulating Hormone (FSH) Levels
timeFrame: Baseline (week -1)
measure: Number of Participants With Anti-drug Antibodies (ADAs)
timeFrame: From week 0 to week 32
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Mesa
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Lynwood
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Riverside
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Riverside
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Dimas
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Arvada
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Ocala
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Winter Park
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Augusta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Monroe
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Greenbelt
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Caro
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Detroit
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Roseville
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Saint Clair Shores
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Minneapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Minnesota
city: Bronx
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Great Neck
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Northport
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Whiteville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Stow
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Allentown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: Novo Nordisk Investigational Site
state: Rhode Island
city: Fort Mill
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Greer
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Knoxville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: North Richland Hills
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Burlington
country: United States
facility: Novo Nordisk Investigational Site
state: Vermont
city: Danville
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Manassas
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Kenosha
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.