Clinical trial NCT01200290: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Kidney Failure, Chronic
Keywords: end stage renal disease
end stage kidney disease
ESRD
Uremia
Renal Dialysis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2010-09-13
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

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)

Primary outcomes:
measure: Change From Baseline in PRA
timeFrame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
measure: Change From Baseline in Arcsine Transformed PRA Scores
timeFrame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76
measure: 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
timeFrame: Baseline through Weeks 24, 52 and 76
Secondary outcomes:
measure: Change From Baseline in Serum Immunoglobulin Levels
timeFrame: Baseline, Weeks 8, 16, 24, 36 and 52
measure: Percent Change From Baseline at Week 1 and Week 24 in Relative Percent of Lymphocytes for B Cell Populations in the Tonsil
timeFrame: Baseline, Weeks 1 and 24
measure: Percent Change From Baseline in Relative Percent of Lymphocytes for B Cell Populations in Peripheral Blood
timeFrame: Baseline, Weeks1, 4, 8, 16, 24, 36, 52, 64 and 76
measure: Percent Change From Baseline in Absolute Counts of B Cell Populations in Peripheral Blood
timeFrame: Baseline, Weeks1, 4, 8, 16, 24, 36 and 52
measure: Population Pharmacokinetics (PK): Constant Clearance
timeFrame: Baseline through Week 24
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: 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.
state: Indiana
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
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.