Safety & Efficacy of Peginesatide for Treatment of Anemia in Participants on Dialysis Not Receiving an ESA

• Sponsor: Affymax (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00680043
• Collaborator: Takeda (Industry)
• Enrollment: 114
• Locations: 11
• Arms: 3
• Duration (Months): 14
• Patients Per Site: 10.4
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of peginesatide for the treatment of anemia in participants with chronic kidney disease who are on dialysis and are not taking any treatment to increase their red blood cell production.

Condition or Disease	Intervention/Treatment	Phase
Anemia; Chronic Renal Failure; Chronic Kidney Disease	Drug: peginesatide; Drug: peginesatide; Drug: Epoetin Alfa	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 (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 equal proportions to two peginesatide treatment regimens, in which participants received peginesatide once every 4 weeks, and one control, epoetin alfa, treatment regimen, in which participants received epoetin alfa three times per week. Total commitment time of this study was a 4 week screening period followed by a minimum of 7 months of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: AFX01-15: A Phase 2, 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) Undergoing Hemodialysis and Not on Erythropoiesis Stimulating Agent (ESA) Treatment
• Study Start Date: Jun 1, 2008
• Actual Primary Completion Date: Aug 1, 2009
• Actual Study Completion Date: Aug 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Peginesatide 0.04 mg/kg	Drug: peginesatide; Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).; Other Names: Omontys Hematide AF37702 Injection
Experimental: Peginesatide 0.08 mg/kg	Drug: peginesatide; Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Omontys Hematide AF37702 Injection
Active Comparator: Epoetin Alfa	Drug: Epoetin Alfa; Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg. The dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.; Other Names: Eprex

Outcome Measures

Primary Outcome Measures

1. Mean Change in Hemoglobin Between Baseline and the Evaluation Period [Baseline and Weeks 21-28]

   The baseline hemoglobin value is defined as the mean of the two most recent hemoglobin values taken prior to the day of randomization plus the value obtained on the day of randomization prior to Dose 1. The mean hemoglobin during the Evaluation period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 21 through 28.

Secondary Outcome Measures

1. Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods [Weeks 1 to 28]

2. Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods [Weeks 1 to 28]

   A hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 g/dL above baseline and a hemoglobin ≥ 11.0 g/dL without RBC or whole blood transfusion during the previous 8 weeks.

Eligibility Criteria

Criteria

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

Inclusion Criteria

1. On hemodialysis for chronic renal failure for at least 2 weeks prior to randomization.

2. Two consecutive hemoglobin values of ≥ 8.0 g/dL and < 11.0 g/dL within the 4 weeks prior to randomization.

Exclusion Criteria

1. Females who are pregnant or breast-feeding.

2. Prior treatment with an erythropoiesis stimulating agent (ESA) in the 12 weeks prior to randomization.

3. Known intolerance to any ESA, parenteral iron supplementation, or pegylated molecule.

4. Known bleeding or coagulation disorder.

5. Known hematologic disease or cause for anemia other than renal disease

6. Poorly controlled hypertension.

7. Evidence of active malignancy within one year.

8. A scheduled kidney transplant.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Facility	Irkutsk		Russian Federation
2	Research Facility	Krasnodar		Russian Federation
3	Research Facility	Krasnoyarsk		Russian Federation
4	Research Facility	Moscow		Russian Federation
5	Research Facility	Nizhniy Novgorod		Russian Federation
6	Research Facility	Omsk		Russian Federation
7	Research Facility	Petrozavodsk		Russian Federation
8	Research Facility	Saratov		Russian Federation
9	Research Facility	St. Petersburg		Russian Federation
10	Research Facility	Tver		Russian Federation
11	Research Facility	Volzhsk		Russian Federation

Sponsors and Collaborators

• Affymax
• Takeda

Investigators

• Study Director: Vice President, Clinical Development, Affymax

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Affymax
• ClinicalTrials.gov Identifier: NCT00680043
• Other Study ID Numbers: AFX01-15
• First Posted: May 19, 2008
• Last Update Posted: Jun 29, 2012
• Last Verified: Jun 1, 2012

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

Study Results

Participant Flow

Arm/Group Title	Peginesatide 0.04 mg/kg	Peginesatide 0.08 mg/kg	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Period Title: Overall Study
STARTED	39	37	38
COMPLETED	37	36	34
NOT COMPLETED	2	1	4

Baseline Characteristics

Arm/Group Title	Peginesatide 0.04 mg/kg	Peginesatide 0.08 mg/kg	Epoetin Alfa	Total
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Total of all reporting groups
Overall Participants	39	37	38	114
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	37 94.9%	31 83.8%	30 78.9%	98 86%
>=65 years	2 5.1%	6 16.2%	8 21.1%	16 14%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.8 (11.71)	48.8 (13.55)	51.4 (14.16)	49.7 (13.10)
Sex: Female, Male (Count of Participants)
Female	12 30.8%	14 37.8%	19 50%	45 39.5%
Male	27 69.2%	23 62.2%	19 50%	69 60.5%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Hemoglobin Between Baseline and the Evaluation Period
Description	The baseline hemoglobin value is defined as the mean of the two most recent hemoglobin values taken prior to the day of randomization plus the value obtained on the day of randomization prior to Dose 1. The mean hemoglobin during the Evaluation period for each participant is calculated as the mean of the available hemoglobin values during Study Weeks 21 through 28.
Time Frame	Baseline and Weeks 21-28

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Peginesatide 0.04 mg/kg	Peginesatide 0.08 mg/kg	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	39	37	38
Baseline [N=39, 37, 38]	9.34 (0.738)	9.20 (0.701)	9.07 (0.739)
Evaluation Period [N=37, 37, 36]	11.45 (1.101)	11.59 (0.943)	11.49 (0.775)
Change from Baseline [N=37, 37, 36]	2.15 (1.038)	2.39 (0.974)	2.41 (0.991)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.04 mg/kg, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 97.5%; -0.79 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.238
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.08 mg/kg, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 97.5%; -0.56 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.238
	Estimation Comments

2. Secondary Outcome

Title	Proportion of Participants Who Receive Red Blood Cell (RBC) or Whole Blood Transfusions During the Correction and Evaluation Periods
Time Frame	Weeks 1 to 28

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Peginesatide 0.04 mg/kg	Peginesatide 0.08 mg/kg	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	39	37	38
Number [percentage of participants]	0.026 0.1%	0.0 0%	0.0 0%

3. Secondary Outcome

Title	Proportion of Participants Achieving Hemoglobin Response During the Correction and Evaluation Periods
Description	A hemoglobin response is defined as a hemoglobin increase of ≥ 1.0 g/dL above baseline and a hemoglobin ≥ 11.0 g/dL without RBC or whole blood transfusion during the previous 8 weeks.
Time Frame	Weeks 1 to 28

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Peginesatide 0.04 mg/kg	Peginesatide 0.08 mg/kg	Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.	Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
Measure Participants	39	37	38
Number [percentage of participants]	0.923 2.4%	0.973 2.6%	1.0 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.04 mg/kg, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Peginesatide 0.08 mg/kg, Epoetin Alfa
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Peginesatide 0.04 mg/kg		Peginesatide 0.08 mg/kg		Epoetin Alfa
Arm/Group Description	Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.04 milligram per kilogram (mg/kg); the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 grams per deciliter (g/dL).		Participants received peginesatide by intravenous injection once every 4 weeks at the starting dose of 0.08 mg/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.		Participants received Epoetin alfa by intravenous injection three times a week at the starting dose of 50 Units/kg; the dose was adjusted throughout the study to maintain a hemoglobin target range of 11.0-12.0 g/dL.
All Cause Mortality
	Peginesatide 0.04 mg/kg		Peginesatide 0.08 mg/kg		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Peginesatide 0.04 mg/kg		Peginesatide 0.08 mg/kg		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/39 (15.4%)		8/37 (21.6%)		4/38 (10.5%)
Blood and lymphatic system disorders
Haemorrhagic anaemia	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Eye disorders
Vitreous haemorrhage	2/39 (5.1%)		0/37 (0%)		0/38 (0%)
Gastrointestinal disorders
Pancreatitis chronic	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
General disorders
Pyrexia	0/39 (0%)		0/37 (0%)		1/38 (2.6%)
Infections and infestations
Appendicitis	0/39 (0%)		0/37 (0%)		1/38 (2.6%)
Bronchitis	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Hepatitis C	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Pneumonia	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Pyelonephritis	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Sinusitis	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis	3/39 (7.7%)		1/37 (2.7%)		2/38 (5.3%)
Humerus fracture	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Postoperative wound complication	0/39 (0%)		0/37 (0%)		1/38 (2.6%)
Radius fracture	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Metabolism and nutrition disorders
Diabetic foot	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Fluid overload	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Renal and urinary disorders
Calculus urinary	0/39 (0%)		0/37 (0%)		1/38 (2.6%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Skin and subcutaneous tissue disorders
Dry gangrene	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Vascular disorders
Diabetic vascular disorder	1/39 (2.6%)		0/37 (0%)		0/38 (0%)
Extremity necrosis	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Hypertension	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Hypertensive crisis	0/39 (0%)		1/37 (2.7%)		0/38 (0%)
Other (Not Including Serious) Adverse Events
	Peginesatide 0.04 mg/kg		Peginesatide 0.08 mg/kg		Epoetin Alfa
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/39 (53.8%)		26/37 (70.3%)		27/38 (71.1%)
Cardiac disorders
Angina pectoris	1/39 (2.6%)		1/37 (2.7%)		4/38 (10.5%)
Palpitations	1/39 (2.6%)		0/37 (0%)		2/38 (5.3%)
Endocrine disorders
Hyperparathyroidism secondary	3/39 (7.7%)		1/37 (2.7%)		4/38 (10.5%)
Gastrointestinal disorders
Diarrhoea	1/39 (2.6%)		2/37 (5.4%)		0/38 (0%)
Erosive duodenitis	0/39 (0%)		0/37 (0%)		2/38 (5.3%)
Gastritis	0/39 (0%)		2/37 (5.4%)		3/38 (7.9%)
Haemorrhoids	0/39 (0%)		2/37 (5.4%)		0/38 (0%)
General disorders
Catheter site inflammation	1/39 (2.6%)		2/37 (5.4%)		0/38 (0%)
Hepatobiliary disorders
Cholecystitis chronic	0/39 (0%)		2/37 (5.4%)		0/38 (0%)
Infections and infestations
Respiratory tract infection	3/39 (7.7%)		3/37 (8.1%)		1/38 (2.6%)
Influenza	0/39 (0%)		2/37 (5.4%)		1/38 (2.6%)
Nasopharyngitis	0/39 (0%)		0/37 (0%)		5/38 (13.2%)
Injury, poisoning and procedural complications
Procedural hypotension	9/39 (23.1%)		4/37 (10.8%)		8/38 (21.1%)
Procedural hypertension	5/39 (12.8%)		4/37 (10.8%)		6/38 (15.8%)
Subcutaneous haematoma	0/39 (0%)		2/37 (5.4%)		0/38 (0%)
Investigations
Blood pressure increased	1/39 (2.6%)		3/37 (8.1%)		2/38 (5.3%)
Gamma-glutamyltransferase increased	1/39 (2.6%)		1/37 (2.7%)		2/38 (5.3%)
Transaminases increased	1/39 (2.6%)		1/37 (2.7%)		2/38 (5.3%)
Metabolism and nutrition disorders
Hypoglycaemia	2/39 (5.1%)		0/37 (0%)		0/38 (0%)
Musculoskeletal and connective tissue disorders
Muscle spasms	3/39 (7.7%)		7/37 (18.9%)		6/38 (15.8%)
Osteoarthritis	3/39 (7.7%)		2/37 (5.4%)		2/38 (5.3%)
Arthralgia	1/39 (2.6%)		2/37 (5.4%)		0/38 (0%)
Osteoporosis	1/39 (2.6%)		0/37 (0%)		2/38 (5.3%)
Nervous system disorders
Headache	3/39 (7.7%)		3/37 (8.1%)		5/38 (13.2%)
Surgical and medical procedures
Arteriovenous fistula operation	1/39 (2.6%)		1/37 (2.7%)		5/38 (13.2%)
Vascular disorders
Hypertension	9/39 (23.1%)		6/37 (16.2%)		5/38 (13.2%)
Hypotension	1/39 (2.6%)		1/37 (2.7%)		6/38 (15.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.