A Study of LY2928057 in Hemodialysis Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Kidney Disease, Chronic
• Intervention / Treatment: Drug: Placebo; Drug: LY2928057

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Lakewood, Colorado, United States, 80228
      • Davita Clinical Research, DN
  • Florida
    • Orlando, Florida, United States, 32806
      • Orlando Clinical Research Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University school of Medicine
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • DaVita Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2928057 (No ESA); 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; Administered intravenously
Experimental: LY2928057 (Reduced ESA); 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; Administered intravenously
Placebo Comparator: Placebo (No ESA); 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; Administered intravenously
Placebo Comparator: Placebo (Reduced ESA); 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; Administered intravenously

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: November 18, 2013
• First Submitted That Met QC Criteria: November 18, 2013
• First Posted (Estimate): November 25, 2013

Study Record Updates

• Last Update Posted (Actual): March 7, 2019
• Last Update Submitted That Met QC Criteria: March 1, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: 15268 (UKCRN); I5M-MC-FABC (Other Identifier: Eli Lilly and Company)