Chronic Renal FailurePhase 3EMERALD 2NCT00597584
Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis
A Phase 3 study testing peginesatide and Epoetin alfa or Epoetin beta in people with Chronic Renal Failure and Chronic Kidney Disease, run by Affymax at 84 sites in 9 countries.
Trial summary
The purpose of this study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis. 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 Epoetin alfa or Epoetin beta
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 823 participants
- Where
- 84 sitesin 9 countries
- Study dates
- Oct 2007to Jan 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
- Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.
- On IV epoetin alfa or beta maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.
- Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the Screening Period.
Who cannot join
- Females who are pregnant or breast-feeding.
- Known intolerance to any erythropoiesis stimulating agent or pegylated molecule or to all parenteral iron supplementation products.
- Known bleeding or coagulation disorder.
- Known hematologic disease or cause of anemia other than renal disease
- Poorly controlled hypertension.
- Evidence of active malignancy within one year prior to randomization.
Show all 9Show fewer
- Temporary (untunneled) dialysis access catheter.
- A scheduled kidney transplant.
- A scheduled surgery that may be expected to lead to significant blood loss.
Trial locations and contacts
84 sites in 9 countries.
84 sites in 9 countries
United States39 sites
Research Facility
Arlington, Texas, 76015
Research Facility
Asheville, North Carolina, 28801
Research Facility
Bakersfield, California, 93309
Research Facility
Brookhaven, Mississippi, 39601
Research Facility
Brooklyn, New York, 11238
Research Facility
Detroit, Michigan, 48202
Research Facility
Detroit, Michigan, 48236
Research Facility
Erie, Pennsylvania, 16507
Research Facility
Fairfax, Virginia, 22033
Research Facility
Flossmoor, Illinois, 60422
Research Facility
Flushing, New York, 11355
Research Facility
Glendale, California, 91205
Research Facility
Hines, Illinois, 60141
Research Facility
Hot Springs, Arkansas, 71901
Research Facility
Houston, Texas, 77099
Research Facility
Lauderdale Lakes, Florida, 33313
Research Facility
Los Angeles, California, 90033
Research Facility
Los Angeles, California, 90048
Research Facility
Los Angeles, California, 90073
Research Facility
Louisville, Kentucky, 40202
Research Facility
McGehee, Arkansas, 71654
Research Facility
Miami, Florida, 33173
Research Facility
Oklahoma City, Oklahoma, 73116
Research Facility
Orangeburg, South Carolina, 29118
Research Facility
Philadelphia, Pennsylvania, 19141
Research Facility
Phoenix, Arizona, 85012
Research Facility
Pine Bluff, Arkansas, 71603
Research Facility
Pinecrest, Florida, 33156
Research Facility
Providence, Rhode Island, 02904
Research Facility
Riverside, California, 92505
Research Facility
Rockville, Maryland, 20850
Research Facility
San Antonio, Texas, 78215
Research Facility
Simi Valley, California, 93065
Research Facility
Springfield, Massachusetts, 01107
Research Facility
The Bronx, New York, 10461
Research Facility
Toledo, Ohio, 43606
Research Facility
Westminster, Colorado, 80031
Research Facility
Whittier, California, 90602
Research Facility
Yuba City, California, 95991
Bulgaria12 sites
Research Facility
Burgas, 8000
Research Facility
Pazardzhik, 4400
Research Facility
Pleven, 5800
Research Facility
Plovdiv, 4000
Research Facility
Plovdiv, 4003
Research Facility
Rousse, 7002
Research Facility
Sofia, 1309
Research Facilities (2)
Sofia, 1431
Research Facility
Sofia, 1527
Research Facility
Sofia, 1606
Research Facility
Varna, 9010
Research Facility
Veliko Tarnovo, 5000
Spain8 sites
Research Facility
Alicante, 03010
Research Facility
Barcelona, 08025
Research Facility
Barcelona, 08902
Research Facility
Barcelona, 08907
Research Facility
Ciudad Real, 13005
Research Facility
Madrid, 28041
Research Facility
Madrid, 28922
Research Facility
Santander, 39008
Italy5 sites
Research Facility
Como, 22100
Research Facility
Cremona, 26100
Research Facility
Lecco, 23900
Research Facility
Modena, 41100
Research Facility
Prato, 59100
United Kingdom5 sites
Research Facility
Carshalton, SM5 1AA
Research Facility
London, E1 1BB
Research Facility
London, SE5 9RS
Research Facility
London, SW17 0QT
Research Facility
Swansea, SA6 6NL
France4 sites
Research Facility
Amiens, 80054
Research Facility
Bordeaux, 33000
Research Facility
Montpellier, 34295
Research Facility
Vannes, 56017
Germany4 sites
Research Facilities (2)
Bremen, 28359
Research Facility
Franfurt, 60528
Research Facility
Hamburg, 22297
Research Facility
Kaiserslautern, 67655
Poland4 sites
Research Facility
Ciechanów, 06-400
Research Facility
Katowice, 40-027
Research Facility
Pabianice, 95-200
Research Facility
Włocławek, 87-800
Romania3 sites
Research Facility
Bucharest, 014461
Research Facility
Bucharest, 050098
Research Facility
Iași, 700503
About this study
Official title: AFX01-14: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin
The purpose of this study was to evaluate the safety and efficacy of peginesatide in the maintenance treatment of anemia in participants on dialysis.
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 (ESAs) 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.
Eligible participants were randomized in a 2:1 ratio to peginesatide administered once every 4 weeks or to continued treatment with epoetin administered 1-3 times each week, respectively. Total commitment time for this study was 4 weeks of screening followed by a minimum of 52 weeks of study treatment.
To evaluate the cardiovascular safety of peginesatide injection, a composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide injection 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, Epoetin alfa or Epoetin beta
- Keywords
- anemia, chronic kidney disease, CKD, chronic renal failure, CRF, dialysis, erythropoietin, EPO, erythropoiesis stimulating agent, ESA, Hematide™, hemodialysis, 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 intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study.
The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
Epoetin alfa or Epoetin betaDrug
Also called Epogen, Neorecormon
Participants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta administered after randomization at Week 0.
The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period.
| Study group | Role | What they receive |
|---|---|---|
| Peginesatide | Experimental | Not described Receives: Drug: peginesatide |
| Epoetin | Active comparator | Not described Receives: Drug: Epoetin alfa or Epoetin beta |
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 five hemoglobin values: the four 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 29 through 36.
Measured: Baseline to Weeks 29-36
Secondary outcomes (2)
Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods
Measured: Weeks 0 to 36
Proportion of Participants Whose Mean Hemoglobin Level During the Evaluation Period is Within the Target Range of 10.0 - 12.0 Grams Per Deciliter (g/dL)
Measured: Weeks 29 to 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2008 (estimated)
- Study startOct 2007
- Primary completionJul 2009
- Study completionJan 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
- 823 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
- NCT00597584
- Sponsor's protocol ID
- AFX01-14
- Other IDs
- 2007-004153-28
- Acronym
- EMERALD 2
- Status last verified
- Mar 2013
- First submitted
- 10 Jan 2008
- Last updated
- 8 Mar 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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 23343061Macdougall 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
Study at a glance
From the registry record, last updated by the sponsor on 8 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- AFX01-14: A Phase 3, Randomized, Active-controlled, Open-label, Multi-center Study of the Safety and Efficacy of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin
- ClinicalTrials.gov ID
- NCT00597584
- Acronym / sponsor ID
- EMERALD 2 / AFX01-14
- Conditions
- Chronic Renal Failure, Chronic Kidney Disease, Anemia
- Keywords
- anemia, chronic kidney disease, CKD, chronic renal failure, CRF, dialysis, erythropoietin, EPO
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 823 participants (actual)
- Lead sponsor
- AffymaxIndustry (pharma, biotech, devices)
- Collaborators
- Takeda
- Study start
- Oct 2007
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 18 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 in the maintenance treatment of anemia in participants on dialysis.
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 (ESAs) 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.
Eligible participants were randomized in a 2:1 ratio to peginesatide administered once every 4 weeks or to continued treatment with epoetin administered 1-3 times each week, respectively. Total commitment time for this study was 4 weeks of screening followed by a minimum of 52 weeks of study treatment.
To evaluate the cardiovascular safety of peginesatide injection, a composite safety endpoint (CSE) was defined for use in prospectively planned analyses which combined cardiovascular safety data from the four Phase 3 peginesatide injection 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
- 2
| Arm | Type | Receives |
|---|---|---|
| Peginesatide | Experimental | Drug: peginesatide |
| Epoetin | Active comparator | Drug: Epoetin alfa or Epoetin beta |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Participants with chronic renal failure on hemodialysis for ≥ 3 months prior to randomization.
- On IV epoetin alfa or beta maintenance therapy continuously prescribed for a minimum of 8 weeks prior to randomization.
- Four consecutive hemoglobin values with a mean ≥ 10.0 and ≤ 12.0 g/dL during the Screening Period.
Key exclusion criteria (9 listed)
- Females who are pregnant or breast-feeding.
- Known intolerance to any erythropoiesis stimulating agent or pegylated molecule or to all parenteral iron supplementation products.
- Known bleeding or coagulation disorder.
- Known hematologic disease or cause of anemia other than renal disease
- Poorly controlled 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 |
|---|---|---|
| peginesatideAlso: Omontys, Hematide, AF37702 InjectionParticipants received peginesatide by intravenous (IV) or subcutaneous (SC) injection once every 4 weeks. The starting dose was based on the participant's total weekly epoetin alfa or beta dose during the last week of the Screening Period; the first dose was administered one week after the last epoetin alfa or beta dose. Participants who received epoetin alfa or beta IV at the time of screening received peginesatide IV during the study, and participants who received epoetin alfa or beta SC at the time of screening received peginesatide SC during the study. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period. | Drug | Peginesatide |
| Epoetin alfa or Epoetin betaAlso: Epogen, NeorecormonParticipants continued to receive commercially available epoetin alfa or beta by intravenous or subcutaneous injection, at the same starting dose, frequency and route of administration as received during the last week of the Screening Period, with the first study dose of epoetin alfa or beta administered after randomization at Week 0. The dose was adjusted to maintain hemoglobin levels in a target range of 10.0-12.0 g/dL and ± 1.5 g/dL from baseline during the Titration and Evaluation Periods, and 10.0-12.0 g/dL during the Long-Term Safety and Efficacy Period. | Drug | Epoetin |
Primary outcome
Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Time frame: Baseline to Weeks 29-36
The baseline hemoglobin value is defined as the mean of five hemoglobin values: the four 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 29 through 36.
2 secondary outcomes
Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods
Time frame: Weeks 0 to 36
Proportion of Participants Whose Mean Hemoglobin Level During the Evaluation Period is Within the Target Range of 10.0 - 12.0 Grams Per Deciliter (g/dL)
Time frame: Weeks 29 to 36
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Mar 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: 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.
- Derived from this study: 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.
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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
84 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing peginesatide and Epoetin alfa or Epoetin beta in people with Chronic Renal Failure and Chronic Kidney Disease, run by Affymax at 84 sites in 9 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 3 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 8 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 84 sites in United States, Bulgaria, Spain, Italy, United Kingdom and 4 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 to Weeks 29-36). 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 NCT00597584, 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 8 Mar 2013.