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A Study in Participants With End-Stage Renal Disease

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ClinicalTrials.gov Identifier: NCT01200290
Recruitment Status : Completed
First Posted : September 13, 2010
Results First Posted : May 14, 2018
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

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.

Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Drug: LY2127399 Phase 2

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  (Clinical Trial)
Actual Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
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 Start Date : April 2011
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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



Primary Outcome Measures :
  1. Change From Baseline in PRA [ Time Frame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76 ]
    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.

  2. Change From Baseline in Arcsine Transformed PRA Scores [ Time Frame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76 ]
    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.

  3. 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 Measures :
  1. Change From Baseline in Serum Immunoglobulin Levels [ Time Frame: Baseline, Weeks 8, 16, 24, 36 and 52 ]
    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.

  2. Percent Change From Baseline at Week 1 and Week 24 in Relative Percent of Lymphocytes for B Cell Populations in the Tonsil [ Time Frame: Baseline, Weeks 1 and 24 ]
    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+).

  3. Percent Change From Baseline in Relative Percent of Lymphocytes for B Cell Populations in Peripheral Blood [ Time Frame: Baseline, Weeks1, 4, 8, 16, 24, 36, 52, 64 and 76 ]
    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+).

  4. Percent Change From Baseline in Absolute Counts of B Cell Populations in Peripheral Blood [ Time Frame: Baseline, Weeks1, 4, 8, 16, 24, 36 and 52 ]
    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+).

  5. Population Pharmacokinetics (PK): Constant Clearance [ Time Frame: Baseline through Week 24 ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01200290


Locations
United States, Indiana
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.
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Eli Lilly and Company
Investigators
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01200290     History of Changes
Other Study ID Numbers: 13710
H9B-MC-BCDR ( Other Identifier: Eli Lilly and Company )
First Posted: September 13, 2010    Key Record Dates
Results First Posted: May 14, 2018
Last Update Posted: May 14, 2018
Last Verified: May 2018

Keywords provided by Eli Lilly and Company:
end stage renal disease
end stage kidney disease
ESRD
Uremia
Renal Dialysis

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Renal Insufficiency
Urologic Diseases
Renal Insufficiency, Chronic
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs