Kidney Failure, ChronicPhase 2NCT01200290

A Study in Participants With End-Stage Renal Disease

A Phase 2 study testing LY2127399 in people with Kidney Failure, Chronic, run by Eli Lilly and Company at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Kidney Failure, Chronic
What is being tested?: LY2127399
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteUnited States
Study dates: Apr 2011to Mar 2014
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Show all 12Show fewer

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)

Trial locations and contacts

1 site in 1 country.

United States1 site

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, 46202

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About this study

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

Read the 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.

Conditions: Kidney Failure, Chronic
Being tested: LY2127399
Keywords: end stage renal disease, end stage kidney disease, ESRD, Uremia, Renal Dialysis
Medical subject headings: Kidney Failure, Chronic, Uremia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LY2127399Drug
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

Study groups in NCT01200290
Study group	Role	What they receive
LY2127399	Experimental	Not described Receives: Drug: LY2127399

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 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.
Measured: 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
Measured: Baseline through Weeks 24, 52 and 76

Secondary outcomes (5)

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.
Measured: 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+).
Measured: 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+).
Measured: 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+).
Measured: 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.
Measured: Baseline through Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2011Mar 2014

First posted13 Sep 2010 (estimated)
Study startApr 2011
Primary completionMar 2014
Study completionMar 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01200290
Sponsor's protocol ID: 13710
Other IDs: H9B-MC-BCDR
Status last verified: May 2018
First submitted: 3 Sep 2010
Last updated: 14 May 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

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.
PubMed 26780484

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 14 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01200290
Acronym / sponsor ID: 13710
Conditions: Kidney Failure, Chronic
Keywords: end stage renal disease, end stage kidney disease, ESRD, Uremia, Renal Dialysis
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Apr 2011
Primary completion: Mar 2014 (actual)
Study completion: Mar 2014 (actual)
First posted: 13 Sep 2010 (estimated)
Results: Posted 14 May 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LY2127399	Experimental	Drug: LY2127399

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

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

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LY2127399120 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	Drug	LY2127399

Primary outcome

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.
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.
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

5 secondary outcomes

Change From Baseline in Serum Immunoglobulin Levels
Time frame: 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
Time frame: Baseline, Weeks 1 and 24
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
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
Population Pharmacokinetics (PK): Constant Clearance
Time frame: Baseline through Week 24

Results and safety

Results posted to the registry on 14 May 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
LY2127399	18	17

Primary outcome: Change From Baseline in PRA

Time frame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76. Mean (Standard Deviation). Unit: percentage of population

Measure	LY2127399 n = 18
Week 8	-0.706 (2.664)
Week 16	-2.176 (3.575)
Week 24	-1.688 (3.240)
Week 36	-2.353 (3.499)
Week 52	-0.529 (3.573)
Week 64	-1.706 (4.497)
Week 76	-2.800 (7.674)

LY2127399: p = 0.324, Mixed Effect Model Repeat Measurement
LY2127399: p = 0.031, Mixed Effect Model Repeat Measurement
LY2127399: p = 0.076, Mixed Effect Model Repeat Measurement

Population analysed: All enrolled participants who received at least 1 dose of study drug, had a non-missing baseline PRA score and at least 1 non-missing post-baseline PRA score.

Primary outcome: Change From Baseline in Arcsine Transformed PRA Scores

Time frame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76. Mean (Standard Deviation). Unit: units on a scale

Measure	LY2127399 n = 18
Week 8	-0.022 (0.086)
Week 16	-0.059 (0.101)
Week 24	-0.060 (0.104)
Week 36	-0.078 (0.099)
Week 52	-0.014 (0.133)
Week 64	-0.053 (0.124)
Week 76	-0.071 (0.158)

LY2127399: p = 0.335, Mixed Effect Model Repeat Measurement
LY2127399: p = 0.043, Mixed Effect Model Repeat Measurement
LY2127399: p = 0.073, Mixed Effect Model Repeat Measurement

Population analysed: All enrolled participants who received at least 1 dose of study drug, had a non-missing baseline PRA score and at least 1 non-missing post-baseline PRA score.

Primary outcome: 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. Count of participants. Unit: Participants

Measure	LY2127399 n = 18
Class I - Week 24	0
Class I - Week 52	0
Class I - Week 76	0
Class II - Week 24	0
Class II - Week 52	0
Class II - Week 76	0

Population analysed: All enrolled participants who received at least 1 dose of study drug and had single antigen reactivity assessed at baseline, during treatment and during follow-up.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LY2127399	9 of 18 (50%)	18 of 18 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26780484Mujtaba 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9AM - 5PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LY2127399 in people with Kidney Failure, Chronic, run by Eli Lilly and Company at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in PRA (time frame: Baseline, Weeks 8, 16, 24, 36, 52, 64 and 76). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01200290, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2018.