Back to resultsA Study of LY2928057 in Hemodialysis Participants
Primary Purpose
Renal Insufficiency, Chronic, Kidney Disease, Chronic
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LY2928057
Placebo
Sponsored by
About this trial
This is an interventional basic science trial for Renal Insufficiency, Chronic
Eligibility Criteria
Inclusion Criteria:
- Participants having end-stage renal disease (ESRD), have received an erythropoiesis stimulating agent (ESA) at least weekly for 2 weeks prior to screening, and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening (that is, an approximate Kt/V greater than 1.1 (K equals dialyzer clearance of urea, t equals dialysis duration time, V equals volume of distribution of urea, which is approximately equal to the participant's total body water) based on the clinical judgment of participant's nephrologist and investigator and who are willing to stop (Parts A and B) or reduce (Part C) their stable ESA dose from the week of randomization until completion of the 6-week treatment period (unless rescue therapy is needed)
- Have a hemoglobin value (taken prior to dialysis if taken on a dialysis day) greater than or equal to 9.5 grams per deciLiter (g/dL) and less than or equal to 12.5 g/dL at screening
- Have a body mass index (BMI) of 18.5 to 45 kilograms per square meter (kg/m^2) inclusive at screening
- Have a transferrin saturation (TSat) greater than or equality to 15 percent and ferritin greater than 40 nanograms per milliliter (ng/mL) at screening
Exclusion Criteria:
- Any cause of anemia other than renal disease
- A history of hyporesponsiveness to ESA
Sites / Locations
- Davita Clinical Research, DN
- Orlando Clinical Research Center
- Indiana University School of Medicine
- Davita Clinical Research
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
LY2928057 (No ESA)
LY2928057 (Reduced ESA)
Placebo (No ESA)
Placebo (Reduced ESA)
Arm Description
Multiple doses of LY2928057 administered intravenously (IV) either once every 2 weeks (Q2W) or once per week (QW) for 6 weeks. Participants discontinued their personal physician-prescribed erythropoiesis stimulating agent (ESA) before treatment.
Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment.
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Outcomes
Primary Outcome Measures
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Change From Baseline in Hemoglobin at 6 Week Endpoint
Secondary Outcome Measures
Pharmacodynamics (PD): Maximum Change in Hemoglobin
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline.
Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
Pharmacodynamics (PD): Maximum Change in Ferritin
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2 days (d), 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose
Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose;
Number of Participants With Anti-LY2928057 Antibodies
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Dialysis did not occur in cycle 1.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01991483
Brief Title
A Study of LY2928057 in Hemodialysis Participants
Official Title
A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
October 2015 (Actual)
Study Completion Date
October 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study will evaluate the safety of LY2928057 and how LY2928057 affects hemoglobin in hemodialysis participants. This study will involve multiple doses of LY2928057 given during a 6 week period either after a participant discontinues or reduces treatment to stimulate red blood cells. This study will last up to 26 weeks for each participant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Renal Insufficiency, Chronic, Kidney Disease, Chronic
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
28 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY2928057 (No ESA)
Arm Type
Experimental
Arm Description
Multiple doses of LY2928057 administered intravenously (IV) either once every 2 weeks (Q2W) or once per week (QW) for 6 weeks. Participants discontinued their personal physician-prescribed erythropoiesis stimulating agent (ESA) before treatment.
Arm Title
LY2928057 (Reduced ESA)
Arm Type
Experimental
Arm Description
Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Arm Title
Placebo (No ESA)
Arm Type
Placebo Comparator
Arm Description
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment.
Arm Title
Placebo (Reduced ESA)
Arm Type
Placebo Comparator
Arm Description
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Intervention Type
Drug
Intervention Name(s)
LY2928057
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Administered intravenously
Primary Outcome Measure Information:
Title
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Description
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time Frame
Baseline to Study Completion (up to Day 137)
Title
Change From Baseline in Hemoglobin at 6 Week Endpoint
Time Frame
Baseline, Day 42
Secondary Outcome Measure Information:
Title
Pharmacodynamics (PD): Maximum Change in Hemoglobin
Time Frame
Baseline through 6 Weeks
Title
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
Description
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline.
Time Frame
Baseline, 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
Time Frame
Baseline through 6 weeks
Title
Pharmacodynamics (PD): Maximum Change in Ferritin
Time Frame
Baseline through 6 weeks
Title
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
Description
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2 days (d), 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose
Time Frame
Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;
Title
Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
Description
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose;
Time Frame
Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose
Title
Number of Participants With Anti-LY2928057 Antibodies
Time Frame
Baseline through 84 days
Title
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
Description
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Dialysis did not occur in cycle 1.
Time Frame
Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants having end-stage renal disease (ESRD), have received an erythropoiesis stimulating agent (ESA) at least weekly for 2 weeks prior to screening, and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening (that is, an approximate Kt/V greater than 1.1 (K equals dialyzer clearance of urea, t equals dialysis duration time, V equals volume of distribution of urea, which is approximately equal to the participant's total body water) based on the clinical judgment of participant's nephrologist and investigator and who are willing to stop (Parts A and B) or reduce (Part C) their stable ESA dose from the week of randomization until completion of the 6-week treatment period (unless rescue therapy is needed)
Have a hemoglobin value (taken prior to dialysis if taken on a dialysis day) greater than or equal to 9.5 grams per deciLiter (g/dL) and less than or equal to 12.5 g/dL at screening
Have a body mass index (BMI) of 18.5 to 45 kilograms per square meter (kg/m^2) inclusive at screening
Have a transferrin saturation (TSat) greater than or equality to 15 percent and ferritin greater than 40 nanograms per milliliter (ng/mL) at screening
Exclusion Criteria:
Any cause of anemia other than renal disease
A history of hyporesponsiveness to ESA
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
Davita Clinical Research, DN
City
Lakewood
State/Province
Colorado
ZIP/Postal Code
80228
Country
United States
Facility Name
Orlando Clinical Research Center
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Indiana University School of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Davita Clinical Research
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
30677788
Citation
Sheetz M, Barrington P, Callies S, Berg PH, McColm J, Marbury T, Decker B, Dyas GL, Truhlar SME, Benschop R, Leung D, Berg J, Witcher DR. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol. 2019 May;85(5):935-948. doi: 10.1111/bcp.13877. Epub 2019 Mar 4.
Results Reference
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A Study of LY2928057 in Hemodialysis Participants
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