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

Novo Nordisk A/S1 site in 1 country61 target enrollmentSeptember 12, 2016

ConditionsAnemia

InterventionsCOR-001 Placebo

DrugsCOR-001

Overview

Phase: Phase 1
Intervention: COR-001
Conditions: Anemia
Sponsor: Novo Nordisk A/S
Enrollment: 61
Locations: 1
Primary Endpoint: Characterization of Maximum Tolerated Dose (MTD)
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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

Registry

clinicaltrials.gov

Start Date

September 12, 2016

End Date

December 11, 2018

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novo Nordisk A/S

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arms & Interventions

COR-001

Intervention: COR-001

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Characterization of Maximum Tolerated Dose (MTD)

Time Frame: Weeks 0-24

The MTD assessment was based on safety data. If more than 2 of 8 active participants in a cohort experience a Dose-Limiting Toxicities (DLT), the MTD was considered to have been exceeded. The DLT threshold was defined using a threshold of greater than or equal to (\>=) Grade 3 events, which includes severe: infusion-related reactions, cardiopulmonary infusion reactions, anaphylaxis, or hypersensitivity. DLTs are defined as follows: 1. Confirmed Grade 3 neutropenia and representing a decline of \> 25% from baseline 2. Serious adverse events (SAEs) of infection in the presence of confirmed Grade 2 or higher new onset lymphopenia or new onset neutropenia. 3. ≥ Grade 3 ALT (Alanine transaminase) or AST(Aspartate transaminase) 4. ≥ Grade 4 hematologic toxicity 5. ≥ Grade 3 non-hematologic toxicity

Change in High-sensitivity C-reactive Protein (hsCRP): Week 4

Time Frame: From baseline (mean of screening and day 1) to week 4

Change from the baseline in hsCRP values to week 4 are presented.

Change in Serum Amyloid A (SAA): Week 4

Time Frame: From baseline (mean of screening and day 1) to week 4

Change from the baseline in serum amyloid A (SAA) values to week 4 are presented.

Secondary Outcomes

Number of Treatment Emergent Adverse Events (TEAEs)(Week 0-24)
Electrocardiogram (ECG)(At baseline, week 6, week 12, week 18 and week 24)
Number of Participants Who Developed Anti-drug Antibodies (ADAs)(Weeks 0-35)
Number of Participants With ADA Titers(Weeks 0-35)
Number of Adverse Events of Special Interest(Weeks 0-24)
Number of Participants With Neutralizing ADAs(From baseline (mean of screening and week 1) to week 35)
Change in High Sensitivity C-reactive Protein (Hs-CRP): Mean of 10-12 Weeks(From baseline (mean of screening and day 1), week 10, week 12)
Change in SAA: Mean of Weeks 10-12(From baseline (mean of screening and day 1), week 10, week 12)
Change in Serum Pre-albumin: Mean of 10-12 Weeks(From baseline (mean of screening and day 1), week 10, week 12)
Change in Albumin: Week 12(From baseline (mean of screening and day 1) to week 12)
Change in Transferrin Saturation (TSAT): Week 4(From baseline (mean of screening and day 1) to week 4)
Change in TSAT: Mean of Weeks 10-12(From baseline (mean of screening and day 1), week 10, week 12)
Change in Reticulocyte Hemoglobin (CHr): Week 4(From baseline (mean of screening and day 1) to week 4)
Change in Erythropoietin Resistance Index (ERI): Week 4(From baseline (weekly mean of screening) to week 4)
Change in ERI: Mean of Weeks 8-12(From baseline (weekly mean of screening), week 8, week 12)
Change in ERI: Mean of Weeks 10-12(From baseline (weekly mean of screening), week 10, week 12)
Change in CHr: Mean of Weeks 10-12(From baseline (mean of screening and day 1), week 10, week 12)
Change in Hemoglobin: Week 4(From baseline (mean of screening and day 1) to week 4)
Change in Hemoglobin: Mean of Weeks 10-12(From baseline (mean of screening and day 1), week 10, week 12)
Change in Hemoglobin: Mean of Weeks 10-12, Excluding Hemoglobin Values Following a Change in the Total Weekly ESA Dose(From baseline (mean of screening and day 1), week 10, week 12)
Change in ERI: Week 12(From baseline (weekly mean of screening) to week 12)
Change in ERI: Mean of Weeks 9-12(From baseline (weekly mean of screening), week 9, week 12)
Change in Hemoglobin: Week 12(From baseline (mean of screening and day 1) to week 12)
Change in Hemoglobin: Week 24(From baseline (mean of screening and day 1) to week 24)
Change in Hemoglobin From Screening to Peak Hemoglobin: Week 4(From screening to week 4)
Basophils: Week 12(At week 12)
Basophil: Week 24(At week 24)
Hypochromatic Red Cells: Week 24(At week 24)
Basophils to Leukocytes Ratio: Week 12(At week 12)
Basophils to Leukocytes Ratio: Week 24(At week 24)
Eosinophils: Week 12(At week 12)
Eosinophils: Week 24(At week 24)
Eosinophils to Leukocytes Ratio: Week 12(At week 12)
Eosinophils to Leukocytes Ratio: Week 24(At week 24)
Erythrocyte Mean Corpuscular HGB Concentration: Week 24(At week 24)
Erythrocyte Mean Corpuscular Volume: Week 12(At week 12)
Erythrocyte Mean Corpuscular Volume: Week 24(At week 24)
Erythrocytes: Week 12(At week 12)
Erythrocytes: Week 24(At week 24)
Hematocrit: Week 12(At week 12)
Hematocrit: Week 24(At week 24)
Hemoglobin: Week 12(At week 12)
Hemoglobin: Week 24(At week 24)
Erythrocyte Mean Corpuscular Hemoglobin: Week 12(At week 12)
Erythrocyte Mean Corpuscular Hemoglobin: Week 24(At week 24)
Erythrocyte Mean Corpuscular Hemoglobin (HGB) Concentration: Week 12(At week 12)
Hypochromatic Red Cells Week 12(At week 12)
Platelets: Week 24(At week 24)
Leukocytes: Week 12(At week 12)
Leukocytes: Week 24(At week 24)
Monocytes to Leukocytes Ratio: Week 24(At week 24)
Neutrophils: Week 12(At week 12)
Neutrophils: Week 24(At week 24)
Neutrophils to Leukocytes Ratio: Week 12(At week 12)
Neutrophils to Leukocytes Ratio: Week 24(At week 24)
Platelets: Week 12(At week 12)
Reticulocytes to Erythrocytes Ratio: Week 12(At week 12)
Reticulocytes to Erythrocytes Ratio: Week 24(At week 24)
Lymphocytes: Week 12(At week 12)
Lymphocytes: Week 24(At week 24)
Lymphocytes to Leukocytes Ratio: Week 12(At week 12)
Lymphocytes to Leukocytes Ratio at Week 24(At week 24)
Monocytes: Week 12(At week 12)
Monocytes: Week 24(At week 24)
Monocytes to Leukocytes Ratio: Week 12(At week 12)
Alanine Aminotransferase: Week 24(At week 24)
Alanine Aminotransferase: Week 12(At week 12)
Albumin: Week 12(At week 12)
Albumin: Week 24(At week 24)
Alkaline Phosphatase: Week 12(At week 12)
Alkaline Phosphatase: Week 24(At week 24)
Aspartate Aminotransferase: Week 12(At week 12)
Aspartate Aminotransferase: Week 24(At week 24)
Bicarbonate: Week 12(At week 12)
Bicarbonate: Week 24(At week 24)
Bilirubin: Week 12(At week 12)
Bilirubin: Week 24(At week 24)
Calcium: Week 12(At week 12)
Calcium: Week 24(At week 24)
Chloride: Week 12(At week 12)
Chloride: Week 24(At week 24)
Cholesterol: Week 12(At week 12)
Cholesterol: Week 24(At week 24)
Creatinine: Week 12(At week 12)
Creatinine: Week 24(At week 24)
Direct Bilirubin: Week 12(At week 12)
Direct Bilirubin: Week 24(At week 24)
Glucose: Week 12(At week 12)
Glucose: Week 24(At week 24)
High-density Lipoprotein (HDL) Cholesterol: Week 12(At week 12)
HDL Cholesterol: Week 24(At week 24)
Hepcidin-25: Week 12(At week 12)
Hepcidin-25: Week 24(At week 24)
Low-density Lipoproteins (LDL) Cholesterol: Week 12(At week 12)
LDL Cholesterol: Week 24(At week 24)
Lipoprotein-a: Week 12(At week 12)
Lipoprotein-a: Week 24(At week 24)
Phosphate: Week 12(At week 12)
Phosphate: Week 24(At week 24)
Potassium: Week 12(At week 12)
Potassium: Week 24(At week 24)
Sodium: Week 12(At week 12)
Sodium: Week 24(At week 24)
Triglycerides: Week 12(At week 12)
Pre-infusion Systolic Blood Pressure: Week 11(At week 11)
Triglycerides: Week 24(At week 24)
Urea Nitrogen: Week 12(At week 12)
Urea Nitrogen: Week 24(At week 24)
Pre-dialysis Body Mass Index (BMI): Week 12(At week 12)
Pre-infusion BMI: Week 11(At week 11)
Pre-dialysis Diastolic Blood Pressure: Week 12(At week 12)
Pre-dialysis Temperature: Week 24(At week 24)
Pre-dialysis Diastolic Blood Pressure: Week 24(At week 24)
Pre-infusion Diastolic Blood Pressure: Week 11(At week 11)
Pre-dialysis Heart Rate: Week 12(At week 12)
Pre-dialysis Systolic Blood Pressure: Week 24(At week 24)
Pre-dialysis Weight: Week 12(At week 12)
Pre-dialysis Heart Rate: Week 24(At week 24)
Pre-infusion Temperature: Week 11(At week 11)
Pre-infusion Heart Rate: Week 11(At week 11)
Pre-dialysis Respiration Rate: Week 12(At week 12)
Pre-dialysis Respiration Rate: Week 24(At week 24)
Pre-infusion Respiration Rate: Week 11(At week 11)
Pre-dialysis Systolic Blood Pressure: Week 12(At week 12)
Pre-infusion Weight: Week 11(At week 11)
Pre-dialysis Temperature: Week 12(At week 12)
Area Under the Serum Concentration Time Curve From Time 0 to Infinity (AUC 0-α) of COR-001(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).)
Elimination Half-life in the Initial Phase (t 1/2,α)(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).)
Elimination Half-life in the Terminal Phase (t 1/2, z)(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).)
Maximum Serum Concentration (Cmax)(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).)
Impact of ADAs on Pharmacokinetics(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).)