Chronic Renal FailurePhase 3PEARL 2NCT00598442
Safety and 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 64 sites in 10 countries.
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
- 493 participants
- Where
- 64 sitesin 10 countries
- Study dates
- Nov 2007to Dec 2009
- 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 milliliters per minute per 1.73 m^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
64 sites in 10 countries.
64 sites in 10 countries
United States42 sites
Research Facility
Ames, Iowa, 50010
Research Facility
Arlington, Texas, 76015
Research Facility
Asheville, North Carolina, 28801
Research Facility
Baton Rouge, Louisiana, 70809
Research Facility
Bend, Oregon, 97701
Research Facility
Burlington, Vermont, 05401
Research Facility
Caldwell, Idaho, 83605
Research Facility
Canton, Georgia, 30114
Research Facility
Chicago, Illinois, 60611
Research Facility
Columbus, Georgia, 31904
Research Facility
Columbus, Ohio, 43210
Research Facility
Detroit, Michigan, 48202
Research Facility
Detroit, Michigan, 48236
Research Facility
Fairfax, Virginia, 22030
Research Facility
Fayetteville, Arkansas, 72703
Research Facility
Flint, Michigan, 48504
Research Facility
Flushing, New York, 11355
Research Facility
Fountain Valley, California, 92708
Research Facility
Fullerton, California, 92835
Research Facility
Granada Hills, California, 91344
Research Facility
Houston, Texas, 77004
Research Facility
Lafayette, Louisiana, 70506
Research Facility
Lauderdale Lakes, Florida, 33313
Research Facility
Los Angeles, California, 90022
Research Facility
Marietta, Georgia, 30060
Research Facility
Meridian, Idaho, 83642
Research Facility
Mishawaka, Indiana, 46545
Research Facility
Morgantown, West Virginia, 26506
Research Facility
Neenah, Wisconsin, 54956
Research Facility
Pembroke Pines, Florida, 33028
Research Facility
Petoskey, Michigan, 49770
Research Facility
Phoenix, Arizona, 85012
Research Facility
Pinecrest, Florida, 33156
Research Facility
Rockville, Maryland, 20852
Research Facility
San Antonio, Texas, 78229
Research Facility
San Diego, California, 92123
Research Facility
Springfield, Massachusetts, 01107
Research Facility
Tacoma, Washington, 98405
Research Facility
Troy, Michigan, 48098
Research Facility
Washington, Missouri, 63090
Research Facility
Whittier, California, 90603
Research Facility
Williamsville, New York, 14221
Bulgaria4 sites
Research Facility
Sofia, 1431
Research Facility
Sofia, 1606
Research Facility
Varna, 9000
Research Facility
Veliko Tarnovo, 5000
Poland4 sites
Research Facility
Bialystok, 15 540
Research Facility
Gdansk, 80 952
Research Facility
Katowice, 40 027
Research Facility
Zamość, 22 400
Czechia3 sites
Research Facility
Prague, 14021
Research Facility
Tábor, 39003
Research Facility
Zdar, 591 01
Hungary3 sites
Research Facility
Balatonfüred, 8230
Research Facility
Kistarcsa, 2143
Research Facility
Szigetvár, 7900
Romania3 sites
Research Facility
Iași, 700 503
Research Facility
Oradea, 410469
Research Facility
Timișoara, 300 736
About this study
Official title: AFX01-13: 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
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 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
Participants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
| 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 Received 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 a 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.
- First posted21 Jan 2008 (estimated)
- Study startNov 2007
- Primary completionJul 2009
- Study completionDec 2009
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
- 493 participants (actual)
Sponsor and investigators
- Lead sponsor
- Affymax
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Takeda
- Responsible party
- Sponsor
- Investigators
- Vice President, Clinical Development, Study director, Affymax
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00598442
- Sponsor's protocol ID
- AFX01-13
- Other IDs
- 2007-004146-32
- Acronym
- PEARL 2
- 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 23343062Fishbane 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
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
- AFX01-13: 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
- NCT00598442
- Acronym / sponsor ID
- PEARL 2 / AFX01-13
- 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
- 493 participants (actual)
- Lead sponsor
- AffymaxIndustry (pharma, biotech, devices)
- Collaborators
- Takeda
- Study start
- Nov 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Dec 2009 (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.
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.
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.
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 milliliters per minute per 1.73 m^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: AranespParticipants received darbepoetin alfa by subcutaneous injection once every 2 weeks, as prescribed. The starting dose was 0.75 microgram per kilogram (mcg/kg) and 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 Received 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
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
64 sites in 10 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 64 sites in 10 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 64 sites in United States, Bulgaria, Poland, Czechia, Hungary and 5 more countries. 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 NCT00598442, 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.