Trial to Evaluate Reduction in Inflammation in Patients With Advanced Chronic Renal Disease Utilizing Antibody Mediated IL-6 Inhibition

Inflammation Clinical Trial

— RESCUE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03926117
• Other study ID #: NN6018-4779
• Status: Completed
• Phase: Phase 2
• Start date: June 3, 2019
• Est. completion date: June 26, 2020

Study information

• Verified date: August 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 264
• Est. completion date: June 26, 2020
• Est. primary completion date: June 26, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Inflammation
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency, Chronic

Intervention

Biological:
• Ziltivekimab
human IgG1k anti-human IL-6 monoclonal antibody

Locations

Country	Name	City	State
United States	Novo Nordisk Investigational Site	Allentown	Pennsylvania
United States	Novo Nordisk Investigational Site	Arvada	Colorado
United States	Novo Nordisk Investigational Site	Asheville	North Carolina
United States	Novo Nordisk Investigational Site	Augusta	Georgia
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Bronx	New York
United States	Novo Nordisk Investigational Site	Burlington	Vermont
United States	Novo Nordisk Investigational Site	Caro	Michigan
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Columbus	Georgia
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Danville	Virginia
United States	Novo Nordisk Investigational Site	Detroit	Michigan
United States	Novo Nordisk Investigational Site	Fort Mill	South Carolina
United States	Novo Nordisk Investigational Site	Great Neck	New York
United States	Novo Nordisk Investigational Site	Greenbelt	Maryland
United States	Novo Nordisk Investigational Site	Greer	South Carolina
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Iowa City	Iowa
United States	Novo Nordisk Investigational Site	Kenosha	Wisconsin
United States	Novo Nordisk Investigational Site	Knoxville	Tennessee
United States	Novo Nordisk Investigational Site	Lynwood	California
United States	Novo Nordisk Investigational Site	Manassas	Virginia
United States	Novo Nordisk Investigational Site	Mesa	Arizona
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Minneapolis	Minnesota
United States	Novo Nordisk Investigational Site	Monroe	Louisiana
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	North Richland Hills	Texas
United States	Novo Nordisk Investigational Site	Northport	New York
United States	Novo Nordisk Investigational Site	Ocala	Florida
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Providence	Rhode Island
United States	Novo Nordisk Investigational Site	Riverside	California
United States	Novo Nordisk Investigational Site	Riverside	California
United States	Novo Nordisk Investigational Site	Roseville	Michigan
United States	Novo Nordisk Investigational Site	Saint Clair Shores	Michigan
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Dimas	California
United States	Novo Nordisk Investigational Site	Stow	Ohio
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina
United States	Novo Nordisk Investigational Site	Wilmington	North Carolina
United States	Novo Nordisk Investigational Site	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

References & Publications (1)

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/ — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in High-sensitivity C-reactive Protein (Hs-CRP) Levels	Percent change from baseline in hs-CRP levels at week 13 are presented.	Baseline (average of the hs-CRP value prior to randomization and day 1), week 13
Secondary	Percent Change From Baseline in Serum Amyloid A (SAA)	Percent change from baseline in SAA at week 13 are presented.	Baseline (average of the values at week -1 and day 1), week 13
Secondary	Percent Change From Baseline in Fibrinogen	Percent change from baseline in fibrinogen at week 13 are presented.	Baseline (day 1), week 13
Secondary	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	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.	From week 0 to week 32
Secondary	Percentage of Participants With Thrombolysis in Myocardial Infarction (TIMI) Major Bleeding Events	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.	From week 0 to week 32
Secondary	Percentage of Participants With Any Treatment-emergent Adverse Events of Special Interest (AESI)	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.	From week 0 to week 32
Secondary	Change in Systolic Blood Pressure (SBP)	Change from baseline in systolic blood pressure at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Diastolic Blood Pressure (DBP)	Change from baseline in diastolic blood pressure at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Respiratory Rate	Change from baseline in respiratory rate at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Body Mass Index (BMI)	Change from baseline in BMI at week 24 are presented.	Baseline (week 1), week 24
Secondary	Change in Heart Rate	Change from baseline in heart rate at Week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Temperature	Change from baseline in temperature at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Electrocardiogram (ECG)	The ECG was assessed by the investigator at baseline (week -1) and week 24 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 24 are presented.	Baseline (week -1), Week 24
Secondary	Change in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AAT) Levels	Change from baseline in ALP, ALT and AAT levels at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Bicarbonate, Chloride, Potassium, Sodium	Change from baseline in bicarbonate, chloride, potassium, sodium at week 32 are presented.	Baseline (week 1), week 32
Secondary	Change in Direct Bilirubin, Bilirubin, Calcium, Creatinine, Glucose, Phosphate and Urea Nitrogen	Change from baseline in direct bilirubin, bilirubin, calcium, creatinine, glucose, phosphate and urea nitrogen at week 32 are presented.	Baseline (week 1), week 32
Secondary	Follicle Stimulating Hormone (FSH) Levels	FSH levels at baseline (week -1) are presented.	Baseline (week -1)
Secondary	Number of Participants With Anti-drug Antibodies (ADAs)	Participants who had at least 1 positive sample (treatment-boosted or treatment-induced) at any time after their first Ziltivekimab administration were classified as positive for ADAs. In the instance that a participant had a positive sample at the baseline visit, the participant was considered positive only if the peak titer of the post-treatment sample was at least 2-fold higher (i.e., >=2-fold) than the titer of the baseline sample. Number of participants positive for antibodies to Ziltivekimab are presented.	From week 0 to week 32