Peginesatide for Maintenance Treatment of Anemia in Participants on Hemodialysis

• Sponsor: Affymax (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00434330
• Collaborator: (none)
• Enrollment: 91
• Locations: 15
• Arms: 6
• Duration (Months): 16
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study was to determine the dose ranges of peginesatide administered intravenously or subcutaneously that maintained hemoglobin in participants on dialysis whose hemoglobin values were stable on epoetin (alfa or beta).

Condition or Disease	Intervention/Treatment	Phase
Anemia; Chronic Kidney Disease; Chronic Renal Failure	Drug: peginesatide; Drug: peginesatide; Drug: peginesatide; Drug: peginesatide; Drug: peginesatide; Drug: peginesatide	Phase 2

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 subjects with chronic kidney disease, and have improved the management of anemia over alternatives such as transfusion. Peginesatide is a parenteral formulation developed for the treatment of anemia associated 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.

Six dose cohorts of 15 participants each were evaluated in this study. Participants received peginesatide injection once every 4 weeks administered intravenously or subcutaneously for a total of 7 doses.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Open-Label, Multi-Center, Dose Finding Study of the Safety, Pharmacodynamics, and Pharmacokinetics of Peginesatide for the Maintenance Treatment of Anemia in Hemodialysis Patients Previously Treated With Epoetin
• Study Start Date: Dec 1, 2006
• Actual Primary Completion Date: Apr 1, 2008
• Actual Study Completion Date: Apr 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1, Q4W, SC, No Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 2, Q4W, IV, No Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 3, Q4W, SC, Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 4, Q4W, IV, Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 5, Q4W, SC, Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Cohort 6, Q4W, IV, Transition	Drug: peginesatide; Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.; Other Names: Omontys Hematide AF37702 Injection

Outcome Measures

Primary Outcome Measures

1. Mean Hemoglobin Throughout the Trial and Mean Hemoglobin Change From Baseline Throughout the Trial. [Baseline and Weeks 2-29]

   The Baseline hemoglobin was the mean of the four most recent mid- or end-of-week predialysis hemoglobin values collected prior to study start. Study start was the date of the first dose of peginesatide injection in participants who did not have a one-week transition period, or the date when Epoetin treatment was first withheld in participants who did have a one-week transition period.

Other Outcome Measures

1. Proportion of Participants With Hemoglobin Within 1.0 g/dL Below Baseline to 1.5 g/dL Above Baseline Throughout the Trial (Weeks 2-29) [Weeks 2 to 29]

   Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within 1 g/dL below to 1.5 g/dL above baseline) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.

2. Proportion of Participants Who Maintained Hemoglobin Within 10 to 12.5 g/dL Throughout the Trial [Weeks 2 to 29]

   Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within the range of 10 g/dL to 12.5 g/dL) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.

3. Proportion of Participants Who Maintain Hemoglobin Within 9.5 to 13.0 g/dL Throughout the Trial [Weeks 2 to 29]

   Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within the range of 9.5 g/dL to 13.0 g/dL) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participant is informed of the investigational nature of this study and has given written, witnessed informed consent in accordance with institutional, local, and national guidelines

• Males or females ≥ 18 years of age. Pre-menopausal females (with the exception of those who are surgically sterile) must have a negative pregnancy test at screening; those who are sexually active must practice a highly effective method of birth control for at least 4 weeks prior to study start, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug

• Clinically stable on hemodialysis for ≥ 3 months prior to study start

• Epoetin (alfa or beta) maintenance therapy, ≥ 50 and ≤ 200 Units/kg/week, at the same dosing frequency, continuously prescribed for 8 weeks prior to study start

• Three mid- or end-of-week hemoglobin values of ≥ 10.0 and ≤ 12.5 grams per deciliter (g/dL) in the 4 weeks prior to study start, with ≤ 1.2 g/dL difference between any of the three values

• One transferrin saturation (TSAT) > 20% within 4 weeks prior to study start

• One ferritin level ≥ 100 ng/mL within 4 weeks prior to study start

• One serum or red cell folate level ≥ lower limit of normal during the 4 weeks prior to study start

• One vitamin B12 level ≥ lower limit of normal during the 4 weeks prior to study start

• One C-reactive protein (CRP) level ≤ 30 mg/L within 4 weeks prior to study start

• Urea clearance/volume (Kt/V) ≥ 1.2 within 4 weeks prior to study start

• One white blood cell count (WBC) ≥ 3.0 x 10^9/L within 4 weeks prior to study start

• One platelet count ≥ 100 x 10^{9/L and ≤ 500 x 10}9/L within 4 weeks prior to study start

Exclusion Criteria:

• Pregnant or breast-feeding participants

• Known intolerance to any erythropoiesis stimulating agent, parenteral iron supplementation or pegylated molecules

• History of antibodies to any erythropoiesis stimulating agent or history of pure red cell aplasia (PRCA)

• Known bleeding or coagulation disorder

• Known hematologic disease (e.g., homozygous sickle-cell disease, thalassemia of all types, multiple myeloma, hemolytic anemia)

• Uncontrolled or symptomatic inflammatory disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, etc.)

• Known history of seizure disorder or received anti-epileptic medication within the previous 6 months

• Uncontrolled or symptomatic secondary hyperparathyroidism, per Investigator's clinical judgment

• Poorly controlled hypertension within 4 weeks prior to study start, per Investigator's clinical judgment

• Chronic congestive heart failure of New York Heart Association class III or IV

• High likelihood of early withdrawal or interruption of the study (e.g., myocardial infarction, severe or unstable coronary artery disease, stroke, respiratory, autoimmune, neuropsychiatric, or neurological abnormalities, liver disease including active hepatitis B or C, active HIV disease, or any other clinically significant medical diseases or conditions in the prior 6 months that may, in the Investigator's opinion, interfere with safety, assessment, or follow-up of the participant)

• Evidence of malignancy within the past 5 years (except non-melanoma skin cancer which is not an exclusion criterion)

• Life expectancy < 12 months

• Temporary (untunneled) dialysis access catheter

• Anticipated elective surgery during the study period, that may be expected to lead to significant blood loss, including vascular access surgery such as an arteriovenous fistula or graft, or a scheduled kidney transplant

• Red blood cell or whole blood transfusion within 12 weeks prior to study start

• Received antibiotics for systemic infection within 2 weeks prior to study start

• Previous exposure to any investigational agent within 6 weeks prior to study start, or planned receipt of an investigational agent, other than as specified by this protocol, during the study period

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Burgas		Bulgaria	8000
2	Research Facility	Pleven		Bulgaria	5800
3	Research Facility	Plovdiv		Bulgaria	4003
4	Research Facility	Rousse		Bulgaria	7002
5	Research Facility	Sofia		Bulgaria	1527
6	Research Facility	Sofia		Bulgaria	1606
7	Research Facility	Sofia		Bulgaria	1709
8	Research Facility	Varna		Bulgaria	9010
9	Research Facility	Veliko Tarnovo		Bulgaria	5000
10	Research Facility	Arad		Romania	310017
11	Research Facility	Bacau		Romania	600114
12	Research Facility	Bucuresti		Romania
13	Research Facility	Iasi		Romania	700503
14	Research Facility	Timisoara		Romania	300736
15	Research Facility	London		United Kingdom	SE5 9RS

Sponsors and Collaborators

• Affymax

Investigators

• Study Director: Vice President, Clinical Development, Affymax, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Affymax
• ClinicalTrials.gov Identifier: NCT00434330
• Other Study ID Numbers: AFX01-07; 2006-002815-28
• First Posted: Feb 13, 2007
• Last Update Posted: Jun 29, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by Affymax: 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
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Anemia

Study Results

Participant Flow

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
Period Title: Overall Study
STARTED	15	15	16	15	15	15
COMPLETED	14	15	13	13	14	14
NOT COMPLETED	1	0	3	2	1	1

Baseline Characteristics

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition	Total
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Total of all reporting groups
Overall Participants	15	15	16	15	15	15	91
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	11 73.3%	10 66.7%	12 75%	13 86.7%	12 80%	12 80%	70 76.9%
>=65 years	4 26.7%	5 33.3%	4 25%	2 13.3%	3 20%	3 20%	21 23.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.4 (12.42)	58.1 (13.91)	46.1 (17.22)	50.4 (12.47)	51.1 (11.43)	53 (13.22)	51.9 (13.74)
Sex: Female, Male (Count of Participants)
Female	9 60%	6 40%	5 31.3%	4 26.7%	6 40%	4 26.7%	34 37.4%
Male	6 40%	9 60%	11 68.8%	11 73.3%	9 60%	11 73.3%	57 62.6%

Outcome Measures

1. Primary Outcome

Title	Mean Hemoglobin Throughout the Trial and Mean Hemoglobin Change From Baseline Throughout the Trial.
Description	The Baseline hemoglobin was the mean of the four most recent mid- or end-of-week predialysis hemoglobin values collected prior to study start. Study start was the date of the first dose of peginesatide injection in participants who did not have a one-week transition period, or the date when Epoetin treatment was first withheld in participants who did have a one-week transition period.
Time Frame	Baseline and Weeks 2-29

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
Measure Participants	15	15	15	15	15	15
Baseline [N=15, 15, 14, 15, 15, 15]	11.10 (0.600)	11.34 (0.596)	11.42 (0.448)	11.19 (0.628)	11.11 (0.810)	11.24 (0.742)
Weeks 2-29 [N=15, 15, 15, 15, 15, 15]	11.64 (0.722)	11.57 (0.771)	11.98 (0.858)	11.86 (0.538)	11.92 (0.699)	11.19 (1.114)
Change from Baseline [N=15, 15, 14, 15, 15, 15]	0.53 (0.600)	0.23 (0.776)	0.57 (0.793)	0.67 (0.752)	0.82 (0.935)	-0.05 (1.000)

2. Other Pre-specified Outcome

Title	Proportion of Participants With Hemoglobin Within 1.0 g/dL Below Baseline to 1.5 g/dL Above Baseline Throughout the Trial (Weeks 2-29)
Description	Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within 1 g/dL below to 1.5 g/dL above baseline) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.
Time Frame	Weeks 2 to 29

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
Measure Participants	15	15	15	15	15	15
Number [percentage of participants]	0.267 1.8%	0.133 0.9%	0.200 1.3%	0.333 2.2%	0.400 2.7%	0.267 1.8%

3. Other Pre-specified Outcome

Title	Proportion of Participants Who Maintained Hemoglobin Within 10 to 12.5 g/dL Throughout the Trial
Description	Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within the range of 10 g/dL to 12.5 g/dL) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.
Time Frame	Weeks 2 to 29

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
Measure Participants	15	15	15	15	15	15
Number [percentage of participants]	0.333 2.2%	0.200 1.3%	0.200 1.3%	0.200 1.3%	0.200 1.3%	0.067 0.4%

4. Other Pre-specified Outcome

Title	Proportion of Participants Who Maintain Hemoglobin Within 9.5 to 13.0 g/dL Throughout the Trial
Description	Hemoglobin relative to baseline: Hemoglobin at a given time point was considered to be not within the specified range (within the range of 9.5 g/dL to 13.0 g/dL) if the hemoglobin value at the time point was not within the range and the next available hemoglobin value within 14 days after the time point also was not within the specified range. These calculations were determined for all time points within a specified time period.
Time Frame	Weeks 2 to 29

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Cohort 1, Q4W, SC, No Transition	Cohort 2, Q4W, IV, No Transition	Cohort 3, Q4W, SC, Transition	Cohort 4, Q4W, IV, Transition	Cohort 5, Q4W, SC, Transition	Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.	Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
Measure Participants	15	15	15	15	15	15
Number [percentage of participants]	0.800 5.3%	0.667 4.4%	0.533 3.3%	0.533 3.6%	0.600 4%	0.600 4%

Adverse Events

Arm/Group Title	Cohort 1, Q4W, SC, No Transition		Cohort 2, Q4W, IV, No Transition		Cohort 3, Q4W, SC, Transition		Cohort 4, Q4W, IV, Transition		Cohort 5, Q4W, SC, Transition		Cohort 6, Q4W, IV, Transition
Arm/Group Description	Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 milligram per kilogram (mg/kg) for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously (SC) once every 4 weeks (Q4W) for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.		Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously (IV) once every 4 weeks for a total of 7 doses. No transition period between epoetin treatment and start of peginesatide treatment.		Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.		Tiered peginesatide starting doses of 0.05, 0.075, or 0.1 mg/kg for participants on an epoetin (alfa or beta) dose of ≤100 Units/kg/week, >100 to 150 Units/kg/week, or >150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.		Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered subcutaneously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.		Tiered peginesatide starting doses of 0.04 mg/kg or 0.075 mg/kg for participants with an epoetin (alfa or beta) dose of ≤100 Units/kg/week or 100 to 150 Units/kg/week, respectively. Doses were administered intravenously once every 4 weeks for a total of 7 doses. With transition period between epoetin treatment and start of peginesatide treatment.
All Cause Mortality
	Cohort 1, Q4W, SC, No Transition		Cohort 2, Q4W, IV, No Transition		Cohort 3, Q4W, SC, Transition		Cohort 4, Q4W, IV, Transition		Cohort 5, Q4W, SC, Transition		Cohort 6, Q4W, IV, Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1, Q4W, SC, No Transition		Cohort 2, Q4W, IV, No Transition		Cohort 3, Q4W, SC, Transition		Cohort 4, Q4W, IV, Transition		Cohort 5, Q4W, SC, Transition		Cohort 6, Q4W, IV, Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		1/15 (6.7%)		3/16 (18.8%)		1/15 (6.7%)		3/15 (20%)		2/15 (13.3%)
Blood and lymphatic system disorders
Anaemia	0/15 (0%)		1/15 (6.7%)		0/16 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Eye disorders
Keratitis	0/15 (0%)		0/15 (0%)		0/16 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)
Uveitis	0/15 (0%)		0/15 (0%)		0/16 (0%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)
General disorders
Sudden death	1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/15 (0%)		1/15 (6.7%)		1/15 (6.7%)
Infections and infestations
Pyelonephritis chronic	0/15 (0%)		0/15 (0%)		2/16 (12.5%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Hepatitis viral	0/15 (0%)		0/15 (0%)		1/16 (6.3%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Pneumonia	1/15 (6.7%)		0/15 (0%)		0/16 (0%)		0/15 (0%)		0/15 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	0/15 (0%)		0/15 (0%)		0/16 (0%)		0/15 (0%)		2/15 (13.3%)		1/15 (6.7%)
Vascular disorders
Penile necrosis	0/15 (0%)		0/15 (0%)		0/16 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1, Q4W, SC, No Transition		Cohort 2, Q4W, IV, No Transition		Cohort 3, Q4W, SC, Transition		Cohort 4, Q4W, IV, Transition		Cohort 5, Q4W, SC, Transition		Cohort 6, Q4W, IV, Transition
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/15 (66.7%)		8/15 (53.3%)		7/16 (43.8%)		8/15 (53.3%)		10/15 (66.7%)		9/15 (60%)
Ear and labyrinth disorders
Vertigo	4/15 (26.7%)		0/15 (0%)		0/16 (0%)		0/15 (0%)		1/15 (6.7%)		0/15 (0%)
Gastrointestinal disorders
Nausea	4/15 (26.7%)		1/15 (6.7%)		2/16 (12.5%)		0/15 (0%)		2/15 (13.3%)		1/15 (6.7%)
Abdominal pain upper	3/15 (20%)		0/15 (0%)		3/16 (18.8%)		0/15 (0%)		0/15 (0%)		1/15 (6.7%)
Abdominal pain	1/15 (6.7%)		2/15 (13.3%)		1/16 (6.3%)		4/15 (26.7%)		1/15 (6.7%)		0/15 (0%)
Vomiting	1/15 (6.7%)		1/15 (6.7%)		0/16 (0%)		1/15 (6.7%)		1/15 (6.7%)		1/15 (6.7%)
Diarrhoea	0/15 (0%)		1/15 (6.7%)		1/16 (6.3%)		1/15 (6.7%)		1/15 (6.7%)		1/15 (6.7%)
General disorders
Chest pain	0/15 (0%)		3/15 (20%)		1/16 (6.3%)		1/15 (6.7%)		0/15 (0%)		0/15 (0%)
Infections and infestations
Bronchitis	4/15 (26.7%)		3/15 (20%)		1/16 (6.3%)		0/15 (0%)		2/15 (13.3%)		1/15 (6.7%)
Tracheobronchitis	3/15 (20%)		1/15 (6.7%)		0/16 (0%)		0/15 (0%)		2/15 (13.3%)		1/15 (6.7%)
Tooth abscess	2/15 (13.3%)		0/15 (0%)		0/16 (0%)		1/15 (6.7%)		2/15 (13.3%)		0/15 (0%)
Hepatitis C	0/15 (0%)		3/15 (20%)		0/16 (0%)		2/15 (13.3%)		0/15 (0%)		0/15 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site haemorrhage	3/15 (20%)		3/15 (20%)		3/16 (18.8%)		1/15 (6.7%)		0/15 (0%)		1/15 (6.7%)
Arteriovenous fistula thrombosis	1/15 (6.7%)		1/15 (6.7%)		2/16 (12.5%)		1/15 (6.7%)		1/15 (6.7%)		0/15 (0%)
Arteriovenous fistula site complication	0/15 (0%)		3/15 (20%)		2/16 (12.5%)		1/15 (6.7%)		1/15 (6.7%)		1/15 (6.7%)
Procedural headache	0/15 (0%)		2/15 (13.3%)		0/16 (0%)		3/15 (20%)		0/15 (0%)		1/15 (6.7%)
Procedural hypertension	0/15 (0%)		2/15 (13.3%)		0/16 (0%)		3/15 (20%)		4/15 (26.7%)		3/15 (20%)
Investigations
Blood pressure increased	4/15 (26.7%)		0/15 (0%)		2/16 (12.5%)		0/15 (0%)		2/15 (13.3%)		0/15 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	5/15 (33.3%)		4/15 (26.7%)		2/16 (12.5%)		4/15 (26.7%)		4/15 (26.7%)		4/15 (26.7%)
Arthralgia	2/15 (13.3%)		0/15 (0%)		2/16 (12.5%)		0/15 (0%)		1/15 (6.7%)		1/15 (6.7%)
Bone pain	2/15 (13.3%)		1/15 (6.7%)		0/16 (0%)		1/15 (6.7%)		2/15 (13.3%)		0/15 (0%)
Nervous system disorders
Headache	9/15 (60%)		4/15 (26.7%)		7/16 (43.8%)		4/15 (26.7%)		5/15 (33.3%)		4/15 (26.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/15 (6.7%)		0/15 (0%)		2/16 (12.5%)		0/15 (0%)		3/15 (20%)		0/15 (0%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	3/15 (20%)		1/15 (6.7%)		3/16 (18.8%)		0/15 (0%)		3/15 (20%)		1/15 (6.7%)
Pruritus	2/15 (13.3%)		0/15 (0%)		1/16 (6.3%)		1/15 (6.7%)		2/15 (13.3%)		0/15 (0%)
Vascular disorders
Hypotension	6/15 (40%)		5/15 (33.3%)		2/16 (12.5%)		2/15 (13.3%)		2/15 (13.3%)		2/15 (13.3%)
Hypertensive crisis	4/15 (26.7%)		6/15 (40%)		2/16 (12.5%)		5/15 (33.3%)		0/15 (0%)		4/15 (26.7%)
Hypertension	2/15 (13.3%)		2/15 (13.3%)		4/16 (25%)		4/15 (26.7%)		1/15 (6.7%)		0/15 (0%)

Limitations/Caveats

Notable issues with some documentation occurred at some of the study sites. In general, overall results excluding the sites with issues were comparable to results based on the full population.

More Information

Certain Agreements

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

Publications may not contain Sponsor confidential information, and will be subject to Sponsor review prior to submission for publication.