A Study of LY2928057 in Hemodialysis Participants

Phase 1

Completed

• Conditions: Kidney Disease, Chronic; Renal Insufficiency, Chronic
• Interventions: Drug: Placebo; Drug: LY2928057

• Registration Number: NCT01991483
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-18
• Study First Submitted QC: 2013-11-18
• Study First Posted: 2013-11-25
• Study Start: 2013-12
• Primary Completion: 2015-10
• Study Completion: 2015-10
• Results First Submitted: 2017-10-21
• Results First Submitted QC: 2018-09-04
• Results First Posted: 2019-02-07
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-01
• Last Update Posted: 2019-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

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Exclusion Criteria

• Any cause of anemia other than renal disease
• A history of hyporesponsiveness to ESA

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo (Reduced ESA)	Placebo	Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Placebo (No ESA)	Placebo	Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment.
LY2928057 (No ESA)	LY2928057	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.
LY2928057 (Reduced ESA)	LY2928057	Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline to Study Completion (up to Day 137)	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	Baseline, Day 42

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics (PD): Maximum Change in Hemoglobin	Baseline through 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): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline	Baseline, 6 weeks	Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline.
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)	Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Ferritin	Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)	Baseline through 6 weeks
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis	Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose	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.
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057	Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;	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	Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose	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	Baseline through 84 days

Trial Locations

Locations (4)

Davita Clinical Research; 🇺🇸 Minneapolis, Minnesota, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States

Davita Clinical Research, DN; 🇺🇸 Lakewood, Colorado, United States

Indiana University School of Medicine; 🇺🇸 Indianapolis, Indiana, United States