Chronic Renal FailurePhase 3PEARL 1NCT00598273

Safety & Efficacy of Peginesatide for the Treatment of Anemia in Participants With Chronic Renal Failure Not on Dialysis

A Phase 3 study testing peginesatide and Darbepoetin alfa in people with Chronic Renal Failure and Chronic Kidney Disease, run by Affymax at 72 sites in 2 countries.

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 study was to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease, who are not on dialysis and not on erythropoiesis stimulating agent (ESA) treatment. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Renal Failure, Chronic Kidney Disease, Anemia
What is being tested?: peginesatide and Darbepoetin alfa
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 490 participants
Where: 72 sitesin 2 countries
Study dates: Oct 2007to Feb 2010
Phase: Phase 3
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

Chronic renal failure with an estimated glomerular filtration rate < 60 milliliter per minute per 1.73m^2 and not expected to begin dialysis for at least 12 weeks.
Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.

Who cannot join

Females who are pregnant or breast-feeding.
Treatment with an ESA in the 12 weeks prior to randomization.
Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.
Prior chronic hemodialysis or chronic peritoneal dialysis treatment.
Known bleeding or coagulation disorder.
Known hematologic disease or cause of anemia other than renal disease

Show all 9Show fewer

Poorly controlled hypertension
Evidence of active malignancy within one year prior to randomization.
A scheduled kidney transplant

Trial locations and contacts

72 sites in 2 countries.

Country

City, postcode or hospital

72 sites in 2 countries

United States68 sites

Research Facility
Allentown, Pennsylvania, 18103
Research Facility
Augusta, Georgia, 30901
Research Facility
Austin, Texas, 78705
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Bakersfield, California, 93309
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Bend, Oregon, 97701
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Bethesda, Maryland, 20814
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Binghamton, New York, 13903
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Bluefield, West Virginia, 24701
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Charlotte, North Carolina, 28208
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Chicago, Illinois, 60616
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Chula Vista, California, 91910
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Clarksville, Tennessee, 37043
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Columbus, Mississippi, 39705
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Corpus Christi, Texas, 78404
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Corsicana, Texas, 75110
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Edinburg, Texas, 78539
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Erie, Pennsylvania, 16507
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Evansville, Indiana, 47714
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Evergreen Park, Illinois, 60805
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Fall River, Massachusetts, 02720
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Glendale, California, 91204
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Great Neck, New York, 11021
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Hines, Illinois, 60141
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Holly Hill, Florida, 32117
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Honolulu, Hawaii, 96817
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Hot Springs, Arkansas, 71901
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Houston, Texas, 77030
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Houston, Texas, 77099
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Hudson, Florida, 34667
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Huntington Beach, California, 92646
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Johnstown, Pennsylvania, 15905
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Kansas City, Missouri, 64128
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Knoxville, Tennessee, 37923
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Lafayette, Indiana, 47904
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Los Angeles, California, 90095
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Miami, Florida, 33173
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Midland, Michigan, 48640
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Mineola, New York, 11501
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Montgomery, Alabama, 36106
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Nashville, Tennessee, 37205
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Northfield, New Jersey, 08225
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Ocala, Florida, 34471
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Oklahoma City, Oklahoma, 73116
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Orange, California, 92868
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Orangeburg, South Carolina, 29118
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Orlando, Florida, 32804
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Paramount, California, 90723
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Pasadena, California, 91106
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Portland, Oregon, 97210
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Providence, Rhode Island, 02904
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Riverside, California, 92505
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Rock Hill, South Carolina, 29732
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Salem, Virginia, 24153
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San Antonio, Texas, 78215
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San Antonio, Texas, 78229
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San Dimas, California, 91773
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Shreveport, Louisiana, 71101
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Stanford, California, 94305-6203
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Tampa, Florida, 33614
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Tempe, Arizona, 85306
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Thornton, Colorado, 80031
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Toms River, New Jersey, 08755
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Washington D.C., District of Columbia, 20037
Research Facility
Whittier, California, 90603
Research Facility
Whittier, California, 90606
Research Facility
Wichita, Kansas, 67214
Research Facility
Worcester, Massachusetts, 01608
Research Facility
Yuba City, California, 95991

Other trials in United States

Puerto Rico4 sites

Research Facility
Caguas, 00725
Research Facility
Ponce, 00716
Research Facility
San Juan, 00909
Research Facility
San Juan, 00918

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About this study

Official title: AFX01-11: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Correction of Anemia in Patients With Chronic Renal Failure (CRF) Not on Dialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment

Read the detailed description

Anemia associated with chronic kidney disease is due to several factors, primarily the inability of the diseased kidneys to produce adequate amounts of endogenous erythropoietin. Ancillary factors include the shortened lifespan of red blood cells, iron and other nutritional deficiencies, infection, and inflammation. The presence and severity of anemia are related to the duration and extent of kidney failure. Anemia is associated with increased mortality, increased likelihood of hospitalization, reduced cognitive function, and increased left ventricular hypertrophy and heart failure.

Erythropoiesis stimulating agents have been established as a treatment for anemia in chronic renal failure subjects, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia in patients with chronic kidney disease. Peginesatide binds to and activates the human erythropoietin receptor and stimulates erythropoiesis in human red cell precursors in a manner similar to other known erythropoiesis-stimulating agents.

Study participants received doses of peginesatide administered once every 4 weeks or darbepoetin alfa administered once every 2 weeks. Total commitment time for this study was a 4 week screening period followed by a minimum of 52 weeks of study treatment. Eligible participants were randomized in equal proportions to two peginesatide treatment regimens and one control, darbepoetin alfa, treatment regimen.

To evaluate the cardiovascular safety of peginesatide, a cardiovascular composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide studies (NCT00598273, NCT00597753, NCT00598442, and NCT00597584). The CSE consisted of six events: death, stroke, myocardial infarction, and serious adverse events of congestive heart failure, unstable angina, and arrhythmia. An independent Event Review Committee (ERC) was used to provide blinded adjudication of potential CSE events.

Conditions: Chronic Renal Failure, Chronic Kidney Disease, Anemia
Being tested: peginesatide, Darbepoetin alfa
Keywords: anemia, chronic kidney disease, CKD, chronic renal failure, CRF, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, Hematide™, hemoglobin, Hb, Hgb, Omontys, peginesatide, red blood cell, red blood cell production
Medical subject headings: Kidney Failure, Chronic, Renal Insufficiency, Chronic, Anemia

What participants receive

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

peginesatideDrug
Also called Omontys, Hematide, AF37702 Injection
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).
peginesatideDrug
Also called Omontys, Hematide, AF37702 Injection
Participants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Darbepoetin alfaDrug
Also called Aranesp
As prescribed, starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.

Study groups in NCT00598273
Study group	Role	What they receive
Peginesatide 0.025 mg/kg	Experimental	Not described Receives: Drug: peginesatide
Peginesatide 0.04 mg/kg	Experimental	Not described Receives: Drug: peginesatide
Darbepoetin Alfa	Active comparator	Not described Receives: Drug: Darbepoetin alfa

What is being measured

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

Mean Change in Hemoglobin Between Baseline and the Evaluation Period
The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.
Measured: Baseline and Weeks 25-36

Secondary outcomes (2)

Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods
Measured: Weeks 0 to 36
Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods.
A hemoglobin response is defined as hemoglobin increase of ≥ 1.0 gram per deciliter (g/dL) above baseline and a hemoglobin ≥ 11.0 g/dL without RBC transfusion during the previous 8 weeks.
Measured: Weeks 0 to 36

Timeline

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

Oct 2007Feb 2010

First posted21 Jan 2008 (estimated)
Study startOct 2007
Primary completionMar 2009
Study completionFeb 2010

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 (2)Papers the sponsor has linked to this study.
Other trials for Chronic Renal FailureStudies of the same condition, open and under way.
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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 490 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00598273
Sponsor's protocol ID: AFX01-11
Acronym: PEARL 1
Status last verified: Feb 2013
First submitted: 10 Jan 2008
Last updated: 12 Feb 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Macdougall IC, Provenzano R, Sharma A, Spinowitz BS, Schmidt RJ, Pergola PE, Zabaneh RI, Tong-Starksen S, Mayo MR, Tang H, Polu KR, Duliege AM, Fishbane S; PEARL Study Groups. Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis. N Engl J Med. 2013 Jan 24;368(4):320-32. doi: 10.1056/NEJMoa1203166.
PubMed 23343062
Fishbane S, Schiller B, Locatelli F, Covic AC, Provenzano R, Wiecek A, Levin NW, Kaplan M, Macdougall IC, Francisco C, Mayo MR, Polu KR, Duliege AM, Besarab A; EMERALD Study Groups. Peginesatide in patients with anemia undergoing hemodialysis. N Engl J Med. 2013 Jan 24;368(4):307-19. doi: 10.1056/NEJMoa1203165.
PubMed 23343061

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 12 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: AFX01-11: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Correction of Anemia in Patients With Chronic Renal Failure (CRF) Not on Dialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment
ClinicalTrials.gov ID: NCT00598273
Acronym / sponsor ID: PEARL 1 / AFX01-11
Conditions: Chronic Renal Failure, Chronic Kidney Disease, Anemia
Keywords: anemia, chronic kidney disease, CKD, chronic renal failure, CRF, erythropoietin, EPO, erythropoiesis stimulating agent
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 490 participants (actual)
Lead sponsor: AffymaxIndustry (pharma, biotech, devices)
Collaborators: Takeda
Study start: Oct 2007
Primary completion: Mar 2009 (actual)
Study completion: Feb 2010 (actual)
First posted: 21 Jan 2008 (estimated)
Results: Posted 30 Jul 2012

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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Peginesatide 0.025 mg/kg	Experimental	Drug: peginesatide
Peginesatide 0.04 mg/kg	Experimental	Drug: peginesatide
Darbepoetin Alfa	Active comparator	Drug: Darbepoetin alfa

Who may qualify

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

Key inclusion criteria (2 listed)

Chronic renal failure with an estimated glomerular filtration rate < 60 milliliter per minute per 1.73m^2 and not expected to begin dialysis for at least 12 weeks.
Two consecutive hemoglobin values ≥ 8.0 g/dL and < 11.0 g/dL within 4 weeks prior to randomization.

Key exclusion criteria (9 listed)

Females who are pregnant or breast-feeding.
Treatment with an ESA in the 12 weeks prior to randomization.
Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.
Prior chronic hemodialysis or chronic peritoneal dialysis treatment.
Known bleeding or coagulation disorder.

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
peginesatideAlso: Omontys, Hematide, AF37702 InjectionParticipants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.025 milligram per kilogram (mg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Drug	Peginesatide 0.025 mg/kg
peginesatideAlso: Omontys, Hematide, AF37702 InjectionParticipants received peginesatide by subcutaneous injection once every 4 weeks. The starting dose was 0.04 mg/kg and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Drug	Peginesatide 0.04 mg/kg
Darbepoetin alfaAlso: AranespAs prescribed, starting dose of 0.75 microgram per kilogram (mcg/kg) administered by subcutaneous injection once every 2 weeks. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Drug	Darbepoetin Alfa

Primary outcome

Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Time frame: Baseline and Weeks 25-36
The baseline hemoglobin value is defined as the mean of three hemoglobin values: the two most recent hemoglobin values taken prior to the day of randomization and the value obtained on the day of randomization. The mean hemoglobin during the Evaluation Period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 25 through 36.

2 secondary outcomes

Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Correction and Evaluation Periods
Time frame: Weeks 0 to 36
Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods.
Time frame: Weeks 0 to 36

Results and safety

Results posted to the registry on 30 Jul 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Peginesatide 0.025 mg/kg	161	120
Peginesatide 0.04 mg/kg	165	127
Darbepoetin Alfa	164	125

Primary outcome: Mean Change in Hemoglobin Between Baseline and the Evaluation Period

Time frame: Baseline and Weeks 25-36. Mean (Standard Deviation). Unit: g/dL

Measure	Peginesatide 0.025 mg/kg n = 161	Peginesatide 0.04 mg/kg n = 165	Darbepoetin Alfa n = 164
Baseline [N=161, 165, 164]	10.05 (0.623)	9.95 (0.685)	10.05 (0.638)
Evaluation Period [N=141, 151, 151]	11.47 (0.731)	11.61 (0.856)	11.47 (0.747)
Change from Baseline [N=141, 151, 151]	1.39 (0.866)	1.64 (0.965)	1.37 (0.861)

Peginesatide 0.025 mg/kg vs Darbepoetin Alfa: Least Squares Mean Difference: 0.03 (97.5% CI -0.19 to 0.26), ANOVA
Peginesatide 0.04 mg/kg vs Darbepoetin Alfa: Least Squares Mean Difference: 0.26 (97.5% CI 0.04 to 0.48), ANOVA

Population analysed: Full Analysis Population: All randomized participants who received at least one dose of study medication

2 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
Peginesatide 0.025 mg/kg	77 of 161 (47.8%)	124 of 161 (77%)	Not reported
Peginesatide 0.04 mg/kg	75 of 165 (45.5%)	123 of 165 (74.5%)	Not reported
Darbepoetin Alfa	71 of 164 (43.3%)	116 of 164 (70.7%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23343062Macdougall IC, Provenzano R, Sharma A, Spinowitz BS, Schmidt RJ, Pergola PE, Zabaneh RI, Tong-Starksen S, Mayo MR, Tang H, Polu KR, Duliege AM, Fishbane S; PEARL Study Groups. Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis. N Engl J Med. 2013 Jan 24;368(4):320-32. doi: 10.1056/NEJMoa1203166.
Derived from this study: PubMed 23343061Fishbane S, Schiller B, Locatelli F, Covic AC, Provenzano R, Wiecek A, Levin NW, Kaplan M, Macdougall IC, Francisco C, Mayo MR, Polu KR, Duliege AM, Besarab A; EMERALD Study Groups. Peginesatide in patients with anemia undergoing hemodialysis. N Engl J Med. 2013 Jan 24;368(4):307-19. doi: 10.1056/NEJMoa1203165.

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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.

Vice President, Clinical Development study director

Affymax

72 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing peginesatide and Darbepoetin alfa in people with Chronic Renal Failure and Chronic Kidney Disease, run by Affymax at 72 sites in 2 countries.

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 9 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 12 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States, Puerto Rico. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 30 Jul 2012). 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?

Mean Change in Hemoglobin Between Baseline and the Evaluation Period (time frame: Baseline and Weeks 25-36). 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 NCT00598273, which also lists 2 linked publications.

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 12 Feb 2013.