Back to resultsA Study in Participants With End-Stage Renal Disease
Primary Purpose
Kidney Failure, Chronic
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LY2127399
Sponsored by
About this trial
This is an interventional other trial for Kidney Failure, Chronic focused on measuring end stage renal disease, end stage kidney disease, ESRD, Uremia, Renal Dialysis
Eligibility Criteria
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)
Sites / Locations
- 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.
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
LY2127399
Arm Description
Outcomes
Primary Outcome Measures
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.
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.
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
Secondary Outcome Measures
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.
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+).
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+).
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+).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01200290
Brief Title
A Study in Participants With End-Stage Renal Disease
Official Title
An Exploratory/Proof of Concept Investigation of the Safety and Pharmacodynamics of LY2127399 in HLA-Presensitized Patients With End-Stage Renal Disease Awaiting Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Failure, Chronic
Keywords
end stage renal disease, end stage kidney disease, ESRD, Uremia, Renal Dialysis
7. Study Design
Primary Purpose
Other
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
LY2127399
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LY2127399
Intervention Description
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
Primary Outcome Measure Information:
Title
Change From Baseline in PRA
Description
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.
Time Frame
Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
Title
Change From Baseline in Arcsine Transformed PRA Scores
Description
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.
Time Frame
Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
Title
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
Time Frame
Baseline through Weeks 24, 52 and 76
Secondary Outcome Measure Information:
Title
Change From Baseline in Serum Immunoglobulin Levels
Description
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.
Time Frame
Baseline, Weeks 8, 16, 24, 36 and 52
Title
Percent Change From Baseline at Week 1 and Week 24 in Relative Percent of Lymphocytes for B Cell Populations in the Tonsil
Description
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+).
Time Frame
Baseline, Weeks 1 and 24
Title
Percent Change From Baseline in Relative Percent of Lymphocytes for B Cell Populations in Peripheral Blood
Description
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+).
Time Frame
Baseline, Weeks1, 4, 8, 16, 24, 36, 52, 64 and 76
Title
Percent Change From Baseline in Absolute Counts of B Cell Populations in Peripheral Blood
Description
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+).
Time Frame
Baseline, Weeks1, 4, 8, 16, 24, 36 and 52
Title
Population Pharmacokinetics (PK): Constant Clearance
Description
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.
Time Frame
Baseline through Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
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.
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26780484
Citation
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.
Results Reference
derived
Learn more about this trial
A Study in Participants With End-Stage Renal Disease
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