Renal Insufficiency, ChronicPhase 1NCT01991483

A Study of LY2928057 in Hemodialysis Participants

A Phase 1 study testing LY2928057 in people with Renal Insufficiency, Chronic and Kidney Disease, Chronic, run by Eli Lilly and Company at 4 sites 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

This study will evaluate the safety of LY2928057 and how LY2928057 affects hemoglobin in hemodialysis participants. This study will involve multiple doses of LY2928057 given during a 6 week period either after a participant discontinues or reduces treatment to stimulate red blood cells. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Renal Insufficiency, Chronic, Kidney Disease, Chronic
What is being tested?: LY2928057
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 28 participants
Where: 4 sitesUnited States
Study dates: Dec 2013to Oct 2015
Phase: Phase 1
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

Participants having end-stage renal disease (ESRD), have received an erythropoiesis stimulating agent (ESA) at least weekly for 2 weeks prior to screening, and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening (that is, an approximate Kt/V greater than 1.1 (K equals dialyzer clearance of urea, t equals dialysis duration time, V equals volume of distribution of urea, which is approximately equal to the participant's total body water) based on the clinical judgment of participant's nephrologist and investigator and who are willing to stop (Parts A and B) or reduce (Part C) their stable ESA dose from the week of randomization until completion of the 6-week treatment period (unless rescue therapy is needed)
Have a hemoglobin value (taken prior to dialysis if taken on a dialysis day) greater than or equal to 9.5 grams per deciLiter (g/dL) and less than or equal to 12.5 g/dL at screening
Have a body mass index (BMI) of 18.5 to 45 kilograms per square meter (kg/m^2) inclusive at screening
Have a transferrin saturation (TSat) greater than or equality to 15 percent and ferritin greater than 40 nanograms per milliliter (ng/mL) at screening

Who cannot join

Any cause of anemia other than renal disease
A history of hyporesponsiveness to ESA

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Indiana University School of Medicine
Indianapolis, Indiana, 46202
Davita Clinical Research, DN
Lakewood, Colorado, 80228
Davita Clinical Research
Minneapolis, Minnesota, 55404
Orlando Clinical Research Center
Orlando, Florida, 32806

Other trials in United States

About this study

Official title: A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients

Conditions: Renal Insufficiency, Chronic, Kidney Disease, Chronic
Being tested: LY2928057, Placebo
Medical subject headings: Renal Insufficiency, Chronic

What participants receive

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

LY2928057Drug
Administered intravenously
PlaceboDrug
Administered intravenously

Study groups in NCT01991483
Study group	Role	What they receive
LY2928057 (No ESA)	Experimental	Multiple doses of LY2928057 administered intravenously (IV) either once every 2 weeks (Q2W) or once per week (QW) for 6 weeks. Participants discontinued their personal physician-prescribed erythropoiesis stimulating agent (ESA) before treatment. Receives: Drug: LY2928057
LY2928057 (Reduced ESA)	Experimental	Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment. Receives: Drug: LY2928057
Placebo (No ESA)	Placebo comparator	Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment. Receives: Drug: Placebo
Placebo (Reduced ESA)	Placebo comparator	Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment. Receives: Drug: Placebo

What is being measured

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

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Measured: Baseline to Study Completion (up to Day 137)
Change From Baseline in Hemoglobin at 6 Week Endpoint
Measured: Baseline, Day 42

Secondary outcomes (14)

Pharmacodynamics (PD): Maximum Change in Hemoglobin
Measured: Baseline through 6 Weeks
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline.
Measured: Baseline, 6 weeks
Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
Measured: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Ferritin
Measured: Baseline through 6 weeks
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2 days (d), 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose
Measured: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;
Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose;
Measured: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose
Number of Participants With Anti-LY2928057 Antibodies
Measured: Baseline through 84 days
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose;
Dialysis did not occur in cycle 1.
Measured: Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose

Timeline

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

Dec 2013Oct 2015

First posted25 Nov 2013 (estimated)
Study startDec 2013
Primary completionOct 2015
Study completionOct 2015

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 Renal Insufficiency, 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 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01991483
Sponsor's protocol ID: 15268
Other IDs: I5M-MC-FABC
Status last verified: Mar 2019
First submitted: 18 Nov 2013
Last updated: 7 Mar 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Sheetz M, Barrington P, Callies S, Berg PH, McColm J, Marbury T, Decker B, Dyas GL, Truhlar SME, Benschop R, Leung D, Berg J, Witcher DR. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol. 2019 May;85(5):935-948. doi: 10.1111/bcp.13877. Epub 2019 Mar 4.
PubMed 30677788

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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All Renal Insufficiency, Chronic trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients
ClinicalTrials.gov ID: NCT01991483
Acronym / sponsor ID: 15268
Conditions: Renal Insufficiency, Chronic, Kidney Disease, Chronic
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Eli Lilly and CompanyIndustry (pharma, biotech, devices)
Study start: Dec 2013
Primary completion: Oct 2015 (actual)
Study completion: Oct 2015 (actual)
First posted: 25 Nov 2013 (estimated)
Results: Posted 7 Feb 2019

Clinical summary

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

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 4

Arm	Type	Receives
LY2928057 (No ESA)	Experimental	Drug: LY2928057Multiple doses of LY2928057 administered intravenously (IV) either once every 2 weeks (Q2W) or once per week (QW) for 6 weeks. Participants discontinued their personal physician-prescribed erythropoiesis stimulating agent (ESA) before treatment.
LY2928057 (Reduced ESA)	Experimental	Drug: LY2928057Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
Placebo (No ESA)	Placebo comparator	Drug: PlaceboMultiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment.
Placebo (Reduced ESA)	Placebo comparator	Drug: PlaceboMultiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.

Who may qualify

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

Key inclusion criteria (4 listed)

Participants having end-stage renal disease (ESRD), have received an erythropoiesis stimulating agent (ESA) at least weekly for 2 weeks prior to screening, and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening (that is, an approximate Kt/V greater than 1.1 (K equals dialyzer clearance of urea, t equals dialysis duration time, V equals volume of distribution of urea, which is approximately equal to the participant's total body water) based on the clinical judgment of participant's nephrologist and investigator and who are willing to stop (Parts A and B) or reduce (Part C) their stable ESA dose from the week of randomization until completion of the 6-week treatment period (unless rescue therapy is needed)
Have a hemoglobin value (taken prior to dialysis if taken on a dialysis day) greater than or equal to 9.5 grams per deciLiter (g/dL) and less than or equal to 12.5 g/dL at screening
Have a body mass index (BMI) of 18.5 to 45 kilograms per square meter (kg/m^2) inclusive at screening
Have a transferrin saturation (TSat) greater than or equality to 15 percent and ferritin greater than 40 nanograms per milliliter (ng/mL) at screening

Key exclusion criteria (2 listed)

Any cause of anemia other than renal disease
A history of hyporesponsiveness to ESA

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
LY2928057Administered intravenously	Drug	LY2928057 (No ESA), LY2928057 (Reduced ESA)
PlaceboAdministered intravenously	Drug	Placebo (No ESA), Placebo (Reduced ESA)

Primary outcome

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time frame: Baseline to Study Completion (up to Day 137)
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Change From Baseline in Hemoglobin at 6 Week Endpoint
Time frame: Baseline, Day 42

14 secondary outcomes

Pharmacodynamics (PD): Maximum Change in Hemoglobin
Time frame: Baseline through 6 Weeks
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
Time frame: Baseline, 6 weeks
Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
Time frame: Baseline through 6 weeks
Pharmacodynamics (PD): Maximum Change in Ferritin
Time frame: Baseline through 6 weeks
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
Time frame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;
Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
Time frame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose
Number of Participants With Anti-LY2928057 Antibodies
Time frame: Baseline through 84 days
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
Time frame: Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose

Results and safety

Results posted to the registry on 7 Feb 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	7	7
300 mg LY2928057	0	0
600 mg LY2928057	0	0
1000 mg LY2928057	0	0

Primary outcome: Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration

Time frame: Baseline to Study Completion (up to Day 137). Count of participants. Unit: Participants

Measure	Placebo n = 7	300 mg LY2928057 n = 6	600 mg LY2928057 n = 11	1000 mg LY2928057 n = 4
Value	0	0	0	0

Population analysed: All participants who received at least one dose of study drug.

Primary outcome: Change From Baseline in Hemoglobin at 6 Week Endpoint

Time frame: Baseline, Day 42. Mean (Standard Deviation). Unit: grams per deciliter (g/dL)

Measure	Placebo n = 7	300 mg LY2928057 n = 5	600 mg LY2928057 n = 9	1000 mg LY2928057 n = 2
Value	-1.674 (0.5535)	-1.739 (0.5261)	-0.906 (0.4577)	-1.623 (1.0469)

Population analysed: All participants who received three doses of study drug, had pharmacodynamics assessment at Week 6, and/or received anti-anemic rescue therapy per protocol, regardless of whether they completed treatment.

14 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
Placebo	0 of 7 (0%)	7 of 7 (100%)	Not reported
300 mg LY2928057	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
600 mg LY2928057	0 of 11 (0%)	8 of 11 (72.7%)	Not reported
1000 mg LY2928057	1 of 4 (25%)	3 of 4 (75%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 30677788Sheetz M, Barrington P, Callies S, Berg PH, McColm J, Marbury T, Decker B, Dyas GL, Truhlar SME, Benschop R, Leung D, Berg J, Witcher DR. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol. 2019 May;85(5):935-948. doi: 10.1111/bcp.13877. Epub 2019 Mar 4.

Related trials for Renal Insufficiency, Chronic

Active, not recruitingPhase 2
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End Stage Renal Disease
RecruitingPhase 3
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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 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director

Eli Lilly and Company

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LY2928057 in people with Renal Insufficiency, Chronic and Kidney Disease, Chronic, run by Eli Lilly and Company at 4 sites 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 4 inclusion and 2 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 7 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 7 Feb 2019). 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?

Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration (time frame: Baseline to Study Completion (up to Day 137)). The study lists 2 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 NCT01991483, 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 7 Mar 2019.