A Study of LY2928057 in Hemodialysis Participants

Study Overview
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Brief Summary
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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.

Official Title
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A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients

Conditions
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Renal Insufficiency, Chronic, Kidney Disease, Chronic

Intervention / Treatment
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* Drug: LY2928057
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2928057 (No ESA)<br>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. | Drug: LY2928057<br>* Administered intravenously<br>|
| Experimental: LY2928057 (Reduced ESA)<br>Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment. | Drug: LY2928057<br>* Administered intravenously<br>|
| Placebo Comparator: Placebo (No ESA)<br>Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment. | Drug: Placebo<br>* Administered intravenously<br>|
| Placebo Comparator: Placebo (Reduced ESA)<br>Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment. | Drug: Placebo<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Study Completion (up to Day 137) | 
| Change From Baseline in Hemoglobin at 6 Week Endpoint |  | Baseline, Day 42 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD): Maximum Change in Hemoglobin |  | Baseline through 6 Weeks | 
| 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. | Baseline, 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Reticulocyte Count |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) |  | Baseline through 6 weeks | 
| Pharmacodynamics (PD): Maximum Change in Ferritin |  | Baseline through 6 weeks | 
| 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 | Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d 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; | Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose | 
| Number of Participants With Anti-LY2928057 Antibodies |  | Baseline through 84 days | 
| 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. | Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose |