A Study in Participants With End-Stage Renal Disease

An Exploratory/Proof of Concept Investigation of the Safety and Pharmacodynamics of LY2127399 in HLA-Presensitized Patients With End-Stage Renal Disease Awaiting Transplantation

The purpose of this trial is to explore the effect of LY2127399 on those antibodies that are a barrier to kidney transplant. Transplantation is currently the definitive treatment for End-Stage Renal Disease (ESRD), providing prolonged survival and improved quality of life.

Study Overview

• Status: Completed
• Conditions: Kidney Failure, Chronic
• Intervention / Treatment: Drug: LY2127399

Detailed Description

In this study, LY2127399 will be tested as a potential treatment to reduce the blood proteins in some participants with ESRD. These proteins are called alloantibodies and are made by the body to react with other proteins on cells of transplanted organs called human leukocyte antigen (HLA) proteins. When a participant has these antibodies, they are referred to as HLA-presensitized. Often the presence of these antibodies, categorized by a method called the panel reactive antibody (PRA), can make a person ineligible to receive a transplant or experience very long wait times on the kidney transplant waiting list. Therefore the need to reduce the antibodies is significant for the successful treatment of ESRD. This study will treat ESRD participants for 6 months with LY2127399 and measure PRA levels for a total of 18 months.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

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:

• Have ESRD and are awaiting kidney transplant
• Have a stable PRA score >50%

Exclusion Criteria:

• Have had a tonsillectomy
• Have a semi-permanent/tunneled catheter
• Have had intravenous immunoglobulin (IVIg) in the past 6 months
• Have had plasmapheresis in the past 6 months
• Uncontrolled hypertension
• Presence of clinically significant cardiac disease in the past 6 months
• Malignancy in the past 5 years, with the exception of cervical, basal cell and squamous epithelial cell cancers
• Have active or recent infection including herpes zoster or herpes simplex in the last 30 days
• Have evidence or suspicion of active Tuberculosis (TB)
• Have had major surgery in the past 2 months
• Have had a serious infection with recovery in the past 3 months
• Have Hepatitis B or C or have Human Immunodeficiency Virus (HIV)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY2127399	Drug: LY2127399; 120 milligrams (mg) administered subcutaneously every 4 weeks for 20 weeks. A loading dose of 240 mg will be given as the first dose of the study medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in PRA	The PRA value is calculated and expressed as a percentage, which can range from 0 % to 100%. The value represents a summation of the total HLA antibody burden that the participant has and how frequently those HLA antigens appear in organ donor population. A calculated PRA of 20% means the participant has antibodies that represent an antigen frequency that exists in approximately 20% of the population.	Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
Change From Baseline in Arcsine Transformed PRA Scores	The PRA value is calculated and expressed as a percentage, which can range from 0% to 100%. The value represents a summation of the total HLA antibody burden that the participant has and how frequently those HLA antigens appear in organ donor population. A calculated PRA of 20% means the participant has antibodies that represent an antigen frequency that exists in approximately 20% of the population. PRA scores were transformed using the arcsine function, which enables a skewed distribution of data typically expressed as proportions to achieve properties closer to a normal distribution. The range of possible arcsine transformed PRA scores is 0 (when PRA = 0) to approximately 1.57 (when PRA =100). Higher scores indicate the participant has antibodies against HLA antigens that appear frequently in the organ donor population.	Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
Number of Participants With a Change From Baseline Positive to Post-Baseline Negative in the Summation of Top 10 Highest Antibody Levels (Class I and Class II Single Antigen Reactivity Reported Separately) During Treatment and Follow-Up		Baseline through Weeks 24, 52 and 76

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Serum Immunoglobulin Levels	Immunoglobulins (Ig), or antibodies, are large molecular weight proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Change from baseline in serum immunoglobulin A (IgA), immunoglobulin G (IgG), IgG1-4, and immunoglobulin M (IgM) levels are reported. A negative change indicates a decrease in Ig levels.	Baseline, Weeks 8, 16, 24, 36 and 52
Percent Change From Baseline at Week 1 and Week 24 in Relative Percent of Lymphocytes for B Cell Populations in the Tonsil	B cell population counts are: Total B cells [cluster designation (CD)19+], mature naïve B cells [CD19+CD27-immunoglobulin D (IgD)+CD10-], switched memory B cells (CD19+CD27+IgD-), unswitched memory B cells (CD19+CD27+IgD+), germinal center B cells Bm2&apos (CD19+CD38+IgD+), germinal center B cells Bm3, Bm4 (CD19+CD38+IgD-), germinal center B cells (CD19+CD38+CD10+CD71+), transitional (Tr) B cells (CD19+CD38++/+++CD24+++/+CD10+) and Tr B cells (CD19+CD27-IgD+CD10+).	Baseline, Weeks 1 and 24
Percent Change From Baseline in Relative Percent of Lymphocytes for B Cell Populations in Peripheral Blood	B cell population counts are: Total B cells (CD19+), mature naïve B cells (CD19+CD27-IgD+CD10-), switched memory B cells (CD19+CD27+IgD-), unswitched memory B cells (CD19+CD27+IgD+), Tr B cells (CD19+CD38++/+++CD24+++/+CD10+) and Tr B cells (CD19+CD27-IgD+CD10+).	Baseline, Weeks1, 4, 8, 16, 24, 36, 52, 64 and 76
Percent Change From Baseline in Absolute Counts of B Cell Populations in Peripheral Blood	B cell population counts are: Total B cells (CD19+), mature naïve B cells (CD19+CD27-IgD+CD10-), switched memory B cells (CD19+CD27+IgD-), unswitched memory B cells (CD19+CD27+IgD+), Tr B cells (CD19+CD38++/+++CD24+++/+CD10+) and Tr B cells (CD19+CD27-IgD+CD10+).	Baseline, Weeks1, 4, 8, 16, 24, 36 and 52
Population Pharmacokinetics (PK): Constant Clearance	Population estimate of constant clearance as determined by population PK analysis. A 2-compartment model was used in PK modeling. Constant clearance is the PK parameter which describes the linear elimination of LY2127399 from serum.	Baseline through Week 24

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

General Publications

• Mujtaba MA, Komocsar WJ, Nantz E, Samaniego MD, Henson SL, Hague JA, Lobashevsky AL, Higgins NG, Czader M, Book BK, Anderson MD, Pescovitz MD, Taber TE. Effect of Treatment With Tabalumab, a B Cell-Activating Factor Inhibitor, on Highly Sensitized Patients With End-Stage Renal Disease Awaiting Transplantation. Am J Transplant. 2016 Apr;16(4):1266-75. doi: 10.1111/ajt.13557. Epub 2016 Jan 18.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: September 3, 2010
• First Submitted That Met QC Criteria: September 10, 2010
• First Posted (Estimate): September 13, 2010

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 11, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: ESRD; Renal Dialysis; end stage renal disease; end stage kidney disease; Uremia
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency, Chronic; Kidney Diseases; Kidney Failure, Chronic; Renal Insufficiency
• Other Study ID Numbers: 13710 (Other Grant/Funding Number: KWF); H9B-MC-BCDR (Other Identifier: Eli Lilly and Company)