Clinical trial NCT02868229: Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001
Official title: A Phase 1/2 Randomized, Double-blind, Placebo Controlled, Cohort Dose-escalation Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anemia
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-08-16
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, pharmacokinetics, and pharmacodynamic effects of multiple doses of COR-001 or placebo


Eligibility criteria: INCLUSION CRITERIA

1. Age greater than or equal to 18 years at the time of signing of the ICF.
2. The patient agrees to comply with the contraception and reproduction restrictions of the study
3. Receiving intravenous (IV) or subcutaneous (SC) erythropoietin stimulating agents (ESA) drugs continuously prescribed for a minimum of 8 weeks prior to Screening
4. At least 2 ferritin values during Screening \> 300 ng/mL
5. At least 2 transferrin saturation (TSAT) values during Screening between 15% and 50% (inclusive)

EXCLUSION CRITERIA:

1. Use of systemic immunosuppressive drugs during the Screening Period or anticipated use of such drugs any time during the study
2. Clinical evidence or suspicion of active or smoldering infection by clinical or serologic criteria
3. Actively treated or active malignancy
4. Known or suspected occult or active bleeding
5. Received a red blood cell or whole blood transfusion within 2 months prior to Screening or anticipated to receive a blood transfusion at any time during the study

Primary outcomes:
measure: Characterization of Maximum Tolerated Dose (MTD)
timeFrame: Weeks 0-24
measure: Change in High-sensitivity C-reactive Protein (hsCRP): Week 4
timeFrame: From baseline (mean of screening and day 1) to week 4
measure: Change in Serum Amyloid A (SAA): Week 4
timeFrame: From baseline (mean of screening and day 1) to week 4
Secondary outcomes:
measure: Number of Adverse Events of Special Interest
timeFrame: Weeks 0-24
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: Week 0-24
measure: Electrocardiogram (ECG)
timeFrame: At baseline, week 6, week 12, week 18 and week 24
measure: Number of Participants Who Developed Anti-drug Antibodies (ADAs)
timeFrame: Weeks 0-35
measure: Number of Participants With ADA Titers
timeFrame: Weeks 0-35
measure: Number of Participants With Neutralizing ADAs
timeFrame: From baseline (mean of screening and week 1) to week 35
measure: Change in Transferrin Saturation (TSAT): Week 4
timeFrame: From baseline (mean of screening and day 1) to week 4
measure: Change in TSAT: Mean of Weeks 10-12
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in Reticulocyte Hemoglobin (CHr): Week 4
timeFrame: From baseline (mean of screening and day 1) to week 4
measure: Change in High Sensitivity C-reactive Protein (Hs-CRP): Mean of 10-12 Weeks
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in SAA: Mean of Weeks 10-12
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in Serum Pre-albumin: Mean of 10-12 Weeks
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in Albumin: Week 12
timeFrame: From baseline (mean of screening and day 1) to week 12
measure: Change in Erythropoietin Resistance Index (ERI): Week 4
timeFrame: From baseline (weekly mean of screening) to week 4
measure: Change in ERI: Mean of Weeks 8-12
timeFrame: From baseline (weekly mean of screening), week 8, week 12
measure: Change in ERI: Mean of Weeks 10-12
timeFrame: From baseline (weekly mean of screening), week 10, week 12
measure: Change in CHr: Mean of Weeks 10-12
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in Hemoglobin: Week 4
timeFrame: From baseline (mean of screening and day 1) to week 4
measure: Change in Hemoglobin: Mean of Weeks 10-12
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in Hemoglobin: Mean of Weeks 10-12, Excluding Hemoglobin Values Following a Change in the Total Weekly ESA Dose
timeFrame: From baseline (mean of screening and day 1), week 10, week 12
measure: Change in ERI: Week 12
timeFrame: From baseline (weekly mean of screening) to week 12
measure: Change in ERI: Mean of Weeks 9-12
timeFrame: From baseline (weekly mean of screening), week 9, week 12
measure: Change in Hemoglobin: Week 12
timeFrame: From baseline (mean of screening and day 1) to week 12
measure: Change in Hemoglobin: Week 24
timeFrame: From baseline (mean of screening and day 1) to week 24
measure: Change in Hemoglobin From Screening to Peak Hemoglobin: Week 4
timeFrame: From screening to week 4
measure: Basophils: Week 12
timeFrame: At week 12
measure: Basophil: Week 24
timeFrame: At week 24
measure: Basophils to Leukocytes Ratio: Week 12
timeFrame: At week 12
measure: Basophils to Leukocytes Ratio: Week 24
timeFrame: At week 24
measure: Eosinophils: Week 12
timeFrame: At week 12
measure: Eosinophils: Week 24
timeFrame: At week 24
measure: Eosinophils to Leukocytes Ratio: Week 12
timeFrame: At week 12
measure: Eosinophils to Leukocytes Ratio: Week 24
timeFrame: At week 24
measure: Erythrocyte Mean Corpuscular Hemoglobin: Week 12
timeFrame: At week 12
measure: Erythrocyte Mean Corpuscular Hemoglobin: Week 24
timeFrame: At week 24
measure: Erythrocyte Mean Corpuscular Hemoglobin (HGB) Concentration: Week 12
timeFrame: At week 12
measure: Erythrocyte Mean Corpuscular HGB Concentration: Week 24
timeFrame: At week 24
measure: Erythrocyte Mean Corpuscular Volume: Week 12
timeFrame: At week 12
measure: Erythrocyte Mean Corpuscular Volume: Week 24
timeFrame: At week 24
measure: Erythrocytes: Week 12
timeFrame: At week 12
measure: Erythrocytes: Week 24
timeFrame: At week 24
measure: Hematocrit: Week 12
timeFrame: At week 12
measure: Hematocrit: Week 24
timeFrame: At week 24
measure: Hemoglobin: Week 12
timeFrame: At week 12
measure: Hemoglobin: Week 24
timeFrame: At week 24
measure: Hypochromatic Red Cells Week 12
timeFrame: At week 12
measure: Hypochromatic Red Cells: Week 24
timeFrame: At week 24
measure: Leukocytes: Week 12
timeFrame: At week 12
measure: Leukocytes: Week 24
timeFrame: At week 24
measure: Lymphocytes: Week 12
timeFrame: At week 12
measure: Lymphocytes: Week 24
timeFrame: At week 24
measure: Lymphocytes to Leukocytes Ratio: Week 12
timeFrame: At week 12
measure: Lymphocytes to Leukocytes Ratio at Week 24
timeFrame: At week 24
measure: Monocytes: Week 12
timeFrame: At week 12
measure: Monocytes: Week 24
timeFrame: At week 24
measure: Monocytes to Leukocytes Ratio: Week 12
timeFrame: At week 12
measure: Monocytes to Leukocytes Ratio: Week 24
timeFrame: At week 24
measure: Neutrophils: Week 12
timeFrame: At week 12
measure: Neutrophils: Week 24
timeFrame: At week 24
measure: Neutrophils to Leukocytes Ratio: Week 12
timeFrame: At week 12
measure: Neutrophils to Leukocytes Ratio: Week 24
timeFrame: At week 24
measure: Platelets: Week 12
timeFrame: At week 12
measure: Platelets: Week 24
timeFrame: At week 24
measure: Reticulocytes to Erythrocytes Ratio: Week 12
timeFrame: At week 12
measure: Reticulocytes to Erythrocytes Ratio: Week 24
timeFrame: At week 24
measure: Alanine Aminotransferase: Week 12
timeFrame: At week 12
measure: Alanine Aminotransferase: Week 24
timeFrame: At week 24
measure: Albumin: Week 12
timeFrame: At week 12
measure: Albumin: Week 24
timeFrame: At week 24
measure: Alkaline Phosphatase: Week 12
timeFrame: At week 12
measure: Alkaline Phosphatase: Week 24
timeFrame: At week 24
measure: Aspartate Aminotransferase: Week 12
timeFrame: At week 12
measure: Aspartate Aminotransferase: Week 24
timeFrame: At week 24
measure: Bicarbonate: Week 12
timeFrame: At week 12
measure: Bicarbonate: Week 24
timeFrame: At week 24
measure: Bilirubin: Week 12
timeFrame: At week 12
measure: Bilirubin: Week 24
timeFrame: At week 24
measure: Calcium: Week 12
timeFrame: At week 12
measure: Calcium: Week 24
timeFrame: At week 24
measure: Chloride: Week 12
timeFrame: At week 12
measure: Chloride: Week 24
timeFrame: At week 24
measure: Cholesterol: Week 12
timeFrame: At week 12
measure: Cholesterol: Week 24
timeFrame: At week 24
measure: Creatinine: Week 12
timeFrame: At week 12
measure: Creatinine: Week 24
timeFrame: At week 24
measure: Direct Bilirubin: Week 12
timeFrame: At week 12
measure: Direct Bilirubin: Week 24
timeFrame: At week 24
measure: Glucose: Week 12
timeFrame: At week 12
measure: Glucose: Week 24
timeFrame: At week 24
measure: High-density Lipoprotein (HDL) Cholesterol: Week 12
timeFrame: At week 12
measure: HDL Cholesterol: Week 24
timeFrame: At week 24
measure: Hepcidin-25: Week 12
timeFrame: At week 12
measure: Hepcidin-25: Week 24
timeFrame: At week 24
measure: Low-density Lipoproteins (LDL) Cholesterol: Week 12
timeFrame: At week 12
measure: LDL Cholesterol: Week 24
timeFrame: At week 24
measure: Lipoprotein-a: Week 12
timeFrame: At week 12
measure: Lipoprotein-a: Week 24
timeFrame: At week 24
measure: Phosphate: Week 12
timeFrame: At week 12
measure: Phosphate: Week 24
timeFrame: At week 24
measure: Potassium: Week 12
timeFrame: At week 12
measure: Potassium: Week 24
timeFrame: At week 24
measure: Sodium: Week 12
timeFrame: At week 12
measure: Sodium: Week 24
timeFrame: At week 24
measure: Triglycerides: Week 12
timeFrame: At week 12
measure: Triglycerides: Week 24
timeFrame: At week 24
measure: Urea Nitrogen: Week 12
timeFrame: At week 12
measure: Urea Nitrogen: Week 24
timeFrame: At week 24
measure: Pre-dialysis Body Mass Index (BMI): Week 12
timeFrame: At week 12
measure: Pre-infusion BMI: Week 11
timeFrame: At week 11
measure: Pre-dialysis Diastolic Blood Pressure: Week 12
timeFrame: At week 12
measure: Pre-dialysis Diastolic Blood Pressure: Week 24
timeFrame: At week 24
measure: Pre-infusion Diastolic Blood Pressure: Week 11
timeFrame: At week 11
measure: Pre-dialysis Heart Rate: Week 12
timeFrame: At week 12
measure: Pre-dialysis Heart Rate: Week 24
timeFrame: At week 24
measure: Pre-infusion Heart Rate: Week 11
timeFrame: At week 11
measure: Pre-dialysis Respiration Rate: Week 12
timeFrame: At week 12
measure: Pre-dialysis Respiration Rate: Week 24
timeFrame: At week 24
measure: Pre-infusion Respiration Rate: Week 11
timeFrame: At week 11
measure: Pre-dialysis Systolic Blood Pressure: Week 12
timeFrame: At week 12
measure: Pre-dialysis Systolic Blood Pressure: Week 24
timeFrame: At week 24
measure: Pre-infusion Systolic Blood Pressure: Week 11
timeFrame: At week 11
measure: Pre-dialysis Weight: Week 12
timeFrame: At week 12
measure: Pre-infusion Weight: Week 11
timeFrame: At week 11
measure: Pre-dialysis Temperature: Week 12
timeFrame: At week 12
measure: Pre-dialysis Temperature: Week 24
timeFrame: At week 24
measure: Pre-infusion Temperature: Week 11
timeFrame: At week 11
measure: Area Under the Serum Concentration Time Curve From Time 0 to Infinity (AUC 0-α) of COR-001
timeFrame: Week 1 (day 1, 3, and 5), Week 2 (day 8), Week 3 (day 15), Week 5 (day 29), Week 7 (day 43), Week 8 (day 50), Week 9 (day 57), Week 11 (day 71 and 75), Week 14 (day 92), Week 18 (day 120) and Week 35 (day 239).
measure: Elimination Half-life in the Initial Phase (t 1/2,α)
timeFrame: Week 1 (day 1, 3, and 5), Week 2 (day 8), Week 3 (day 15), Week 5 (day 29), Week 7 (day 43), Week 8 (day 50), Week 9 (day 57), Week 11 (day 71 and 75), Week 14 (day 92), Week 18 (day 120) and Week 35 (day 239).
measure: Elimination Half-life in the Terminal Phase (t 1/2, z)
timeFrame: Week 1 (day 1, 3, and 5), Week 2 (day 8), Week 3 (day 15), Week 5 (day 29), Week 7 (day 43), Week 8 (day 50), Week 9 (day 57), Week 11 (day 71 and 75), Week 14 (day 92), Week 18 (day 120) and Week 35 (day 239).
measure: Maximum Serum Concentration (Cmax)
timeFrame: Week 1 (day 1, 3, and 5), Week 2 (day 8), Week 3 (day 15), Week 5 (day 29), Week 7 (day 43), Week 8 (day 50), Week 9 (day 57), Week 11 (day 71 and 75), Week 14 (day 92), Week 18 (day 120) and Week 35 (day 239).
measure: Impact of ADAs on Pharmacokinetics
timeFrame: Week 1 (day 1, 3, and 5), Week 2 (day 8), Week 3 (day 15), Week 5 (day 29), Week 7 (day 43), Week 8 (day 50), Week 9 (day 57), Week 11 (day 71 and 75), Week 14 (day 92), Week 18 (day 120) and Week 35 (day 239).
Other outcomes:
Locations:
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Hollywood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Augusta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: North Brunswick
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Astoria
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Fresh Meadows
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: Providence
country: United States
facility: Novo Nordisk Investigational Site
state: Rhode Island
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Transparency (dept. 1452)
role: STUDY_DIRECTOR
References:
citation: Pergola PE, Devalaraja M, Fishbane S, Chonchol M, Mathur VS, Smith MT, Lo L, Herzog K, Kakkar R, Davidson MH. Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. J Am Soc Nephrol. 2021 Jan;32(1):211-222. doi: 10.1681/ASN.2020050595. Epub 2020 Dec 3.