Clinical trial NCT01991483: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Insufficiency, Chronic
Kidney Disease, Chronic
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-11-25
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline to Study Completion (up to Day 137)
measure: Change From Baseline in Hemoglobin at 6 Week Endpoint
timeFrame: Baseline, Day 42
Secondary outcomes:
measure: Pharmacodynamics (PD): Maximum Change in Hemoglobin
timeFrame: Baseline through 6 Weeks
measure: Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
timeFrame: Baseline, 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
timeFrame: Baseline through 6 weeks
measure: Pharmacodynamics (PD): Maximum Change in Ferritin
timeFrame: Baseline through 6 weeks
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
timeFrame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;
measure: Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
timeFrame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose
measure: Number of Participants With Anti-LY2928057 Antibodies
timeFrame: Baseline through 84 days
measure: Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
timeFrame: Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose
Other outcomes:
Locations:
city: Lakewood
country: United States
facility: Davita Clinical Research, DN
state: Colorado
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
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.