Title
Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001
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
Phase
Phase 1/Phase 2Lead Sponsor
Corvidia TherapeuticsStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
AnemiaIntervention/Treatment
ziltivekimab ...Study Participants
61This 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
INCLUSION CRITERIA Age greater than or equal to 18 years at the time of signing of the ICF. The patient agrees to comply with the contraception and reproduction restrictions of the study Receiving intravenous (IV) or subcutaneous (SC) erythropoietin stimulating agents (ESA) drugs continuously prescribed for a minimum of 8 weeks prior to Screening At least 2 ferritin values during Screening > 300 ng/mL At least 2 transferrin saturation (TSAT) values during Screening between 15% and 50% (inclusive) EXCLUSION CRITERIA: Use of systemic immunosuppressive drugs during the Screening Period or anticipated use of such drugs any time during the study Clinical evidence or suspicion of active or smoldering infection by clinical or serologic criteria Actively treated or active malignancy Known or suspected occult or active bleeding 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
| Event Type | Organ System | Event Term | Placebo | COR-001 2 mg | COR-001 6 mg | COR-001 20 mg |
|---|
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: Confirmed Grade 3 neutropenia and representing a decline of > 25% from baseline Serious adverse events (SAEs) of infection in the presence of confirmed Grade 2 or higher new onset lymphopenia or new onset neutropenia. ≥ Grade 3 ALT (Alanine transaminase) or AST(Aspartate transaminase) ≥ Grade 4 hematologic toxicity ≥ Grade 3 non-hematologic toxicity
Change from the baseline in hsCRP values to week 4 are presented.
Change from the baseline in serum amyloid A (SAA) values to week 4 are presented.
An AE (adverse event) is any undesirable event or any untoward medical occurrence that occurs to a participant during the course of a study, or the protocol-defined time after study termination, whether or not that event is considered Study Drug-related. A TEAE was defined as an AE that initiated or worsened on or after the date of first dose of study drug up to the end of study. Number of TEAEs from baseline until the end of safety follow up (week 24) were presented.
A summary of the overall ECG interpretation and clinical significance from baseline until the end of the safety follow up period (week 24) is presented and categorized as Normal, Abnormal clinically significant (CS), Abnormal non clinically significant (NCS) and Missing.
Number of participants who developed ADAs from baseline until the end of the extended follow up period (week 35) were reported. Samples with detectable ADAs were classified as positive for ADAs. Samples without detectable ADAs were classified as negative for ADAs.
Number of participants with ADA titers for ADA-positive samples from baseline to week 35 is presented.
Number of participants with neutralizing ADAs from baseline to week 35 are presented.
Change from baseline in TSAT to week 4 is presented.
Change from baseline in TSAT to the mean of weeks 10-12 is presented.
Change from baseline in CHr to week 4 is presented.
Change from baseline in hs-CRP to the mean of 10-12 weeks is presented.
Change from baseline in SAA to the mean of weeks 10-12 is presented.
The observed values of bicarbonate at week 24 are presented.
Change from baseline in ERI to week 4 is presented. ERI is defined as the epoetin alfa-equivalent dose (weight-based per week in U/kg) divided by the serum hemoglobin (in g/dL).
Change from baseline in serum pre-albumin to the mean of 10-12 weeks is presented.
Change from baseline in albumin to week 12 is presented.
The observed values of bilirubin at week 12 are presented.
Change from baseline in ERI to the mean of weeks 8-12 is presented. ERI is defined as the epoetin alfa-equivalent dose (weight-based per week in U/kg) divided by the serum hemoglobin (in g/dL).
Change from baseline in ERI to the mean of weeks 10-12 is presented. ERI is defined as the epoetin alfa-equivalent dose (weight-based per week in U/kg) divided by the serum hemoglobin (in g/dL).
Change from baseline in CHr to the mean of weeks 10-12 is presented.
Change from baseline in hemoglobin to week 4 is presented.
Change from baseline in hemoglobin to weeks 10-12 is presented.
The observed values of bilirubin at week 24 are presented.
The observed values of calcium at week 12 are presented.
The observed values of calcium at week 24 are presented.
The observed values of chloride at week 12 are presented.
Change from baseline in hemoglobin to weeks 10-12, excluding hemoglobin values following a change in the total weekly ESA (erythropoiesis stimulating agent) dose is presented. A change is defined as the first time when the ESA weekly dose goes up by >25% or down by >25% relative to the previous week's dose.
Change from baseline in ERI to week 12 is presented. ERI is defined as the epoetin alfa-equivalent dose (weight-based per week in U/kg) divided by the serum hemoglobin (in g/dL).
The observed values of chloride at week 24 are presented.
The observed values of cholesterol at week 12 are presented.
Change from baseline in ERI to the mean of weeks 9-12 is presented. ERI is defined as the epoetin alfa-equivalent dose (weight-based per week in U/kg) divided by the serum hemoglobin (in g/dL).
Change from baseline in hemoglobin to week 12 is presented.
Change from baseline in hemoglobin to week 24 is presented.
Change in hemoglobin from screening to peak hemoglobin at week 4 is presented.
The observed values of basophils at week 12 are presented.
The observed values of basophils at week 24 are presented.
Basophils to leukocytes ratio at week 12 is presented.
Basophils to leukocytes ratio at week 24 is presented.
The observed values of cholesterol at week 24 are presented.
The observed values of eosinophils at week 24 are presented.
Eosinophils to leukocytes ratio at week 12 is presented.
The eosinophils to leukocytes ratio at week 24 is presented.
The observed values of erythrocyte mean corpuscular hemoglobin at week 12 are presented.
The observed values of erythrocyte mean corpuscular hemoglobin at week 24 are presented.
The observed values of erythrocyte mean corpuscular HGB concentration at week 12 are presented.
The observed values of erythrocyte mean corpuscular HGB concentration at week 24 are presented.
The observed values of erythrocyte mean corpuscular volume at week 12 are presented.
The observed values of erythrocyte mean corpuscular volume at week 24 are presented.
The observed values of erythrocytes at week 12 are presented.
The observed values of erythrocytes at week 24 are presented.
The observed values of hematocrit at week 12 are presented.
The observed values of hematocrit at week 24 are presented.
The observed values of hemoglobin at week 12 are presented.
The observed values of hemoglobin at week 24 are presented.
The observed values of hypochromatic red cells at week 12 are presented.
The observed values of hypochromatic red cells at week 24 are presented.
The observed values of leukocytes at week 12 are presented.
The observed values of leukocytes at week 24 are presented.
The observed values of lymphocytes at week 12 are presented.
The observed values of lymphocytes at week 24 are presented.
The observed values of creatinine at week 12 are presented.
Lymphocytes to leukocytes ratio at week 12 is presented.
Lymphocytes to leukocytes ratio at week 24 is presented.
The observed values of creatinine at week 24 are presented.
The observed values of monocytes at week 12 are presented.
The observed values of monocytes at week 24 are presented.
Monocytes to leukocytes ratio at week 12 is presented.
Monocytes to leukocytes ratio at week 24 is presented.
The observed values of neutrophils at week 12 are presented.
The observed values of neutrophils at week 24 are presented.
Neutrophils to leukocytes ratio at week 12 is presented.
Neutrophils to leukocytes ratio at week 24 is presented.
The observed values of platelets at week 12 are presented.
The observed values of platelets at week 24 are presented.
Reticulocytes to erythrocytes ratio at week 12 is presented.
Reticulocytes to erythrocytes ratio at week 24 is presented.
The observed values of alanine aminotransferase at week 12 are presented.
The observed values of alanine aminotransferase at week 24 are presented.
The observed values of albumin at week 12 are presented.
The observed values of albumin at week 24 are presented.
The observed values of alkaline phosphatase at week 12 are presented.
The observed values of alkaline phosphatase at week 24 are presented.
The observed values of aspartate aminotransferase at week 12 are presented.
The observed values of aspartate aminotransferase at week 24 are presented.
The observed values of bicarbonate at week 12 are presented.
The observed values of direct bilirubin at week 12 are presented.
The observed values of direct bilirubin at week 24 are presented.
The observed values of glucose at week 12 are presented.
The observed values of glucose at week 24 are presented.
The observed values of HDL cholesterol at week 12 are presented.
The observed values of HDL cholesterol at week 24 are presented.
The observed values of hepcidin-25 at week 12 are presented.
The observed values of hepcidin-25 at week 24 are presented.
The observed values of LDL cholesterol at week 12 are presented.
The observed values of LDL cholesterol at week 24 are presented.
The observed values of triglyceride at week 12 are presented.
The observed values of triglycerides at week 24 are presented.
The observed values of lipoprotein-a at week 12 are presented.
The observed values of lipoprotein-a at week 24 are presented.
The observed values of phosphate at week 12 are presented.
The observed values of phosphate at week 24 are presented.
The observed values of potassium at week 12 are presented.
The observed values of potassium at week 24 are presented.
The observed values of sodium at week 12 are presented.
The observed values of urea nitrogen at week 12 are presented.
The observed values of urea nitrogen at week 24 are presented.
Pre-dialysis BMI values at week 12 are presented.
Pre-infusion BMI values at week 11 are presented.
Pre-dialysis diastolic blood pressure values at week 12 are presented.
Pre-dialysis diastolic blood pressure values at week 24 are presented.
Pre-infusion diastolic blood pressure values at week 11 are presented.
Pre-dialysis heart rate values at week 12 are presented.
Pre-dialysis heart rate values at week 24 are presented.
Pre-infusion heart rate values at week 11 are presented.
Pre-dialysis respiration rate values at week 12 are presented.
Pre-dialysis respiration rate values at week 24 are presented.
Pre-infusion respiration rate values at week 11 are presented.
Pre-dialysis values of systolic blood pressure at week 12 are presented.
Pre-dialysis values of systolic blood pressure at week 24 are presented.
Pre-infusion systolic blood pressure values at week 11 are presented.
Pre-dialysis weight values at week 12 are presented.
Pre-infusion weight values at week 11 are presented.
Pre-dialysis temperature values at week 12 are presented.
Pre-dialysis temperature values at week 24 are presented.
Pre-infusion temperature values at week 11 are presented.
Area under the serum concentration time curve from time 0 to infinity (AUC 0-α) of COR-001 is presented.
Elimination half-life in the initial phase (t 1/2,α) is presented from week 0 to week 35.
Elimination half-life in the terminal phase(t 1/2, z) is presented from week 0 to week 35.
Maximum serum concentration (Cmax) of COR-001 from week 0 to week 35 is presented.
The observed values of sodium at week 24 are presented.
Presence of ADA was a covariate for pharmacokinetics (PK) affecting V1 (volume of distribution for the central compartment). Impact of ADAs on V1 from baseline to week 35 is presented. In the below table, result presented is the bootstrap parameter estimate of the effect of ADA on V1 for a PK model that includes data for all arms combined.
The observed values of eosinophils at week 12 are presented.
Frequency of events of interest by treatment group and dose from baseline until the end of the safety follow-up period (week 24) were reported. Adverse events of special interest included severe infusion-related reactions, hypersensitivity reaction during study drug infusion, anaphylaxis and neutropenia events of grade 2 or higher (i.e., absolute neutrophil count <1500/mm^3 and decline by at least 25% from baseline).
