Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Conditions:	Chronic Renal Failure Chronic Kidney Disease Anemia
Interventions:	Drug: peginesatide Drug: Epoetin alfa or Epoetin beta

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
Peginesatide	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 grams per deciliter (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	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.

Description

Peginesatide

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 grams per deciliter (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

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.

Participant Flow: Overall Study

	Peginesatide	Epoetin
STARTED	549 ^[1]	274
COMPLETED	421	211
NOT COMPLETED	128	63
Adverse Event	4	2
Death	53	30
Lack of Efficacy	1	0
Lost to Follow-up	2	4
Physician Decision	3	0
Pregnancy	2	0
Withdrawal by Subject	44	12
Discontinued Dialysis	0	1
Lost ability to consent	1	1
Never dosed	1	0
Relocation	8	6
Renal transplant	9	7

[1]	Randomization was 2:1 peginesatide to epoetin

Baseline Characteristics

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Reporting Groups

	Description
Peginesatide	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 grams per deciliter (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	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.
Total	Total of all reporting groups

Description

Peginesatide

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 grams per deciliter (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

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.

Total

Total of all reporting groups

Baseline Measures

	Peginesatide	Epoetin	Total
Number of Participants [units: participants]	542	273	815
Age ^[1] [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	350	173	523
>=65 years	192	100	292
Age [units: years] Mean ± Standard Deviation	58.8 ± 14.47	58.6 ± 13.73	58.8 ± 14.22
Gender [units: participants]
Female	211	120	331
Male	331	153	484

[1]	Eight participants were excluded from the full analysis population: 7 participants in the Peginesatide group and 1 participant in the Epoetin group. These 8 participants did not receive study medication.

Outcome Measures

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1. Primary:

Mean Change in Hemoglobin Between Baseline and the Evaluation Period [ Time Frame: Baseline to Weeks 29-36 ]

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2. Secondary:

Proportion of Participants Who Receive Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods [ Time Frame: Weeks 0 to 36 ]

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3. Secondary:

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 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The first publication of the primary safety and efficacy results will include data from all appropriate study sites. Either after the first multicenter publication, or following 36 months after the completion of the study, Investigators are free to publish; such publications may not contain Sponsor Confidential Information and may be subject to Sponsor review 60 days prior to submission for publication.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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Results Point of Contact:

Name/Title: Vice President, Clinical Development
Organization: Affymax
phone: 650-812-8700
e-mail: info@affymax.com

Publications of Results:

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.

Publications automatically indexed to this study:

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.

Responsible Party:	Affymax
ClinicalTrials.gov Identifier:	NCT00597584 History of Changes
Other Study ID Numbers:	AFX01-14, 2007-004153-28
Study First Received:	January 10, 2008
Results First Received:	April 26, 2012
Last Updated:	March 6, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board Bulgaria: Bulgarian Drug Agency Bulgaria: Ethics committee Germany: Federal Institute for Drugs and Medical Devices Germany: Ethics Commission Italy: The Italian Medicines Agency Italy: Ethics Committee Poland: The Central Register of Clinical Trials Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Poland: Ethics Committee Romania: National Medicines Agency Romania: Ethics Committee United Kingdom: Medicines and Healthcare Products Regulatory Agency United Kingdom: Research Ethics Committee France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) France: Committee for the Protection of Personnes Spain: Agencia Española de Medicamentos y Productos Sanitarios Spain: Comité Ético de Investigación Clínica

Safety & Efficacy of Peginesatide for Maintenance Treatment of Anemia in Participants With Chronic Kidney Disease on Hemodialysis (EMERALD 2)