Extension Study to Evaluate Safety and Tolerability of Peginesatide for Long-Term Treatment of Anemia in Participants With CKD (EU)

• Sponsor: Affymax (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00453973
• Collaborator: (none)
• Enrollment: 114
• Locations: 20
• Arms: 2
• Duration (Months): 34
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study was to evaluate the long term safety and tolerability of peginesatide for the maintenance of hemoglobin in participants with chronic kidney disease (CKD) who had received at least 24 weeks of peginesatide treatment in an earlier study.

Condition or Disease	Intervention/Treatment	Phase
Chronic Renal Failure; Chronic Kidney Disease; Anemia	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 (ESAs) 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.

Study participants had received at least 24 weeks of peginesatide dosing in a previous Affymax-sponsored study and were to receive doses of peginesatide for up to 54 months. However, the Sponsor ended the study early.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multi-Center, Extension Study to Evaluate the Safety and Tolerability of Peginesatide for the Long-Term Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Sep 1, 2009
• Actual Study Completion Date: Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maintenance Switch in Dialysis Participants Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). This group is categorized as "Maintenance Switch in Dialysis Participants" regardless of dialysis status at the start of or during this study.	Drug: peginesatide; Participants received the same initial peginesatide dose via the same route, intravenously or subcutaneously, as was administered at the end of the previous peginesatide treatment study in which the participant was enrolled. The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. Each participant was to receive peginesatide as an injection administered once every 4 weeks for approximately 54 months in this trial.; Other Names: Omontys Hematide AF37702 Injection
Experimental: Treatment Initiation in Non-Dialysis Participants Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). This group is categorized as "Initiation of Treatment in Non-Dialysis Participants" regardless of dialysis status at the start of or during this study.	Drug: peginesatide; Participants received the same initial peginesatide dose via the same route, intravenously or subcutaneously, as was administered at the end of the previous peginesatide treatment study in which the participant was enrolled. The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. Each participant was to receive peginesatide as an injection administered once every 4 weeks for approximately 54 months in this trial.; Other Names: Omontys Hematide AF37702 Injection

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change [Up to 54 months]

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, informed consent in accordance with institutional, local, and national guidelines.

• Males or females ≥ 18 years of age.

• Premenopausal 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 drug administration, and must be willing to continue contraception until at least 4 weeks after the last dose of study drug.

• Participant who has received at least 24 weeks of peginesatide dosing in a previous Affymax-sponsored study.

• One hemoglobin value of ≥ 10.0 grams per deciliter (g/dL) in the 4 weeks prior to study drug administration.

Exclusion Criteria:

• Known intolerance to peginesatide or pegylated products.

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

• High likelihood of early withdrawal or interruption of the study (e.g., participant suffers from any clinically significant medical disease or condition that may, in the Investigator's opinion, interfere with safety, assessment, or follow-up of the participant)

• Anticipated life expectancy < 18 months

• Receipt of any ESA other than peginesatide at any time after participant enrollment in the previous Affymax-sponsored study

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	Varna		Bulgaria	9010
6	Research Facility	Veliko Tarnovo		Bulgaria	5000
7	Research Facility	Białystok		Poland	15-540
8	Research Facility	Katowice		Poland	40-027
9	Research Facility	Łódź		Poland	90-153
10	Research Facility	Arad		Romania	310017
11	Research Facility	Bacau		Romania	600114
12	Research Facility	Bucuresti		Romania	014461
13	Research Facility	Iasi		Romania	700506
14	Research Facility	Timisoara		Romania	300736
15	Research Facility	Croydon		United Kingdom	CR7 7YE
16	Research Facility	Derby		United Kingdom	DE22 3NE
17	Research Facility	London		United Kingdom	E1 1BB
18	Research Facility	London		United Kingdom	SES 9RS
19	Research Facility	London		United Kingdom	SW17 0QT
20	Research Facility	Swansea		United Kingdom	SA6 6NL

Sponsors and Collaborators

• Affymax

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: NCT00453973
• Other Study ID Numbers: AFX01-10; 2006-003846-41
• First Posted: Mar 29, 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	Maintenance Switch in Dialysis Participants	Treatment Initiation in Non-Dialysis Participants
Arm/Group Description	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. This group is categorized as "Maintenance Switch in Dialysis Participants" regardless of dialysis status at the start of or during this study.	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. This group is categorized as "Initiation of Treatment in Non-Dialysis Participants" regardless of dialysis status at the start of or during this study.
Period Title: Overall Study
STARTED	51	63
COMPLETED	0	15
NOT COMPLETED	51	48

Baseline Characteristics

Arm/Group Title	Maintenance Switch in Dialysis Participants	Treatment Initiation in Non-Dialysis Participants	Pooled AF37702 Inj.
Arm/Group Description	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. This group is categorized as "Maintenance Switch in Dialysis Participants" regardless of dialysis status at the start of or during this study.	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. This group is categorized as "Initiation of Treatment in Non-Dialysis Participants" regardless of dialysis status at the start of or during this study.
Overall Participants	51	63	114
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	42 82.4%	22 34.9%	64 56.1%
>=65 years	9 17.6%	41 65.1%	50 43.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.2 (11.92)	66.4 (13.48)	60.5 (14.36)
Sex: Female, Male (Count of Participants)
Female	19 37.3%	34 54%	53 46.5%
Male	32 62.7%	29 46%	61 53.5%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Mean Hemoglobin in the Target Range of 10.0-12.0 Grams Per Deciliter (g/dL) After Final Dosing Guideline Change
Time Frame	Up to 54 months

Outcome Measure Data

Analysis Population Description

Full Analysis - Number of participants with hemoglobin assessed after dosing guideline change

Arm/Group Title	Maintenance Switch in Dialysis Participants	Treatment Initiation in Non-Dialysis Participants
Arm/Group Description	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. This group is categorized as "Maintenance Switch in Dialysis Participants" regardless of dialysis status at the start of or during this study.	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. This group is categorized as "Initiation of Treatment in Non-Dialysis Participants" regardless of dialysis status at the start of or during this study.
Measure Participants	28	40
Number [percentage of participants]	0.786 1.5%	0.875 1.4%

Adverse Events

Arm/Group Title	Maintenance Switch in Dialysis Participants		Treatment Initiation in Non-Dialysis Participants
Arm/Group Description	Participants were from a prior Affymax peginesatide treatment study conducted in participants who were on dialysis and had been on Epoetin at study entry, and who were switched to peginesatide (NCT00434330). The median first dose at study start was 0.044 milligram per kilogram (mg/kg) with an interquartile range of 0.028 to 0.076 mg/kg. This group is categorized as "Maintenance Switch in Dialysis Participants" regardless of dialysis status at the start of or during this study.		Participants were from a prior Affymax peginesatide treatment study conducted in participants who were not on dialysis and not on erythropoiesis stimulating agents (ESAs), and who received peginesatide (NCT00228436). The median first dose at study start was 0.024 mg/kg with an interquartile range of 0.017 to 0.035 mg/kg. This group is categorized as "Initiation of Treatment in Non-Dialysis Participants" regardless of dialysis status at the start of or during this study.
All Cause Mortality
	Maintenance Switch in Dialysis Participants		Treatment Initiation in Non-Dialysis Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Maintenance Switch in Dialysis Participants		Treatment Initiation in Non-Dialysis Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/51 (19.6%)		31/63 (49.2%)
Cardiac disorders
Atrial fibrillation	2/51 (3.9%)		1/63 (1.6%)
Acute coronary syndrome	0/51 (0%)		2/63 (3.2%)
Acute myocardial infarction	0/51 (0%)		2/63 (3.2%)
Cardiac arrest	0/51 (0%)		2/63 (3.2%)
Angina pectoris	0/51 (0%)		1/63 (1.6%)
Angina unstable	0/51 (0%)		1/63 (1.6%)
Aortic valve disease	0/51 (0%)		1/63 (1.6%)
Cardiac tamponade	1/51 (2%)		0/63 (0%)
Cardiogenic shock	1/51 (2%)		0/63 (0%)
Cardiopulmonary failure	1/51 (2%)		0/63 (0%)
Myocardial infarction	0/51 (0%)		1/63 (1.6%)
Myocardial ischaemia	0/51 (0%)		1/63 (1.6%)
Pericardial haemorrhage	1/51 (2%)		0/63 (0%)
Gastrointestinal disorders
Abdominal adhesions	0/51 (0%)		1/63 (1.6%)
Abdominal pain	0/51 (0%)		1/63 (1.6%)
Gastrointestinal haemorrhage	0/51 (0%)		1/63 (1.6%)
Peritonitis	0/51 (0%)		1/63 (1.6%)
General disorders
Catheter related complication	0/51 (0%)		2/63 (3.2%)
Pyrexia	0/51 (0%)		1/63 (1.6%)
Hepatobiliary disorders
Cholecystitis acute	0/51 (0%)		1/63 (1.6%)
Infections and infestations
Pneumonia	1/51 (2%)		1/63 (1.6%)
Urinary tract infection	0/51 (0%)		2/63 (3.2%)
Arteriovenous fistula site infection	1/51 (2%)		0/63 (0%)
Bronchopneumonia	0/51 (0%)		1/63 (1.6%)
Catheter site infection	0/51 (0%)		1/63 (1.6%)
Diabetic foot infection	0/51 (0%)		1/63 (1.6%)
Herpes zoster	0/51 (0%)		1/63 (1.6%)
Infected skin ulcer	0/51 (0%)		1/63 (1.6%)
Localised infection	1/51 (2%)		0/63 (0%)
Lower respiratory tract infection	0/51 (0%)		1/63 (1.6%)
Lung infection	1/51 (2%)		0/63 (0%)
Pyelonephritis chronic	1/51 (2%)		0/63 (0%)
Sepsis	0/51 (0%)		1/63 (1.6%)
Staphylococcal sepsis	1/51 (2%)		0/63 (0%)
Injury, poisoning and procedural complications
Arteriovenous fistula site complication	0/51 (0%)		1/63 (1.6%)
Femur fracture	0/51 (0%)		1/63 (1.6%)
Joint sprain	1/51 (2%)		0/63 (0%)
Investigations
Haemoglobin decreased	0/51 (0%)		1/63 (1.6%)
Metabolism and nutrition disorders
Hyperkalaemia	1/51 (2%)		3/63 (4.8%)
Dehydration	0/51 (0%)		1/63 (1.6%)
Diabetic foot	0/51 (0%)		1/63 (1.6%)
Diabetic ketoacidosis	0/51 (0%)		1/63 (1.6%)
Hypercalcaemia	0/51 (0%)		1/63 (1.6%)
Hyperglycaemia	0/51 (0%)		1/63 (1.6%)
Malnutrition	0/51 (0%)		1/63 (1.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	0/51 (0%)		1/63 (1.6%)
Nervous system disorders
Basal ganglia haemorrhage	1/51 (2%)		0/63 (0%)
Cerebrovascular accident	0/51 (0%)		1/63 (1.6%)
Lacunar infarction	0/51 (0%)		1/63 (1.6%)
Ruptured cerebral aneurysm	0/51 (0%)		1/63 (1.6%)
Psychiatric disorders
Confusional state	0/51 (0%)		1/63 (1.6%)
Renal and urinary disorders
Renal failure chronic	0/51 (0%)		2/63 (3.2%)
Azotaemia	0/51 (0%)		1/63 (1.6%)
Renal failure	0/51 (0%)		1/63 (1.6%)
Renal failure acute	0/51 (0%)		1/63 (1.6%)
Renal impairment	0/51 (0%)		1/63 (1.6%)
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema	1/51 (2%)		1/63 (1.6%)
Respiratory failure	0/51 (0%)		1/63 (1.6%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/51 (0%)		2/63 (3.2%)
Skin necrosis	0/51 (0%)		1/63 (1.6%)
Vascular disorders
Hypertension	0/51 (0%)		2/63 (3.2%)
Deep vein thrombosis	0/51 (0%)		1/63 (1.6%)
Extremity necrosis	0/51 (0%)		1/63 (1.6%)
Haematoma	1/51 (2%)		0/63 (0%)
Hypertensive crisis	1/51 (2%)		0/63 (0%)
Other (Not Including Serious) Adverse Events
	Maintenance Switch in Dialysis Participants		Treatment Initiation in Non-Dialysis Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	46/51 (90.2%)		55/63 (87.3%)
Cardiac disorders
Angina pectoris	3/51 (5.9%)		2/63 (3.2%)
Ear and labyrinth disorders
Vertigo	4/51 (7.8%)		1/63 (1.6%)
Endocrine disorders
Hyperparathyroidism secondary	4/51 (7.8%)		0/63 (0%)
Gastrointestinal disorders
Nausea	10/51 (19.6%)		10/63 (15.9%)
Abdominal pain	9/51 (17.6%)		3/63 (4.8%)
Abdominal pain upper	6/51 (11.8%)		1/63 (1.6%)
Diarrhoea	5/51 (9.8%)		4/63 (6.3%)
Vomiting	5/51 (9.8%)		5/63 (7.9%)
Toothache	4/51 (7.8%)		0/63 (0%)
Constipation	0/51 (0%)		4/63 (6.3%)
General disorders
Chest pain	5/51 (9.8%)		1/63 (1.6%)
Catheter site haemorrhage	4/51 (7.8%)		0/63 (0%)
Influenza like illness	2/51 (3.9%)		4/63 (6.3%)
Fatigue	1/51 (2%)		6/63 (9.5%)
Oedema peripheral	1/51 (2%)		12/63 (19%)
Infections and infestations
Bronchitis	9/51 (17.6%)		7/63 (11.1%)
Tracheobronchitis	6/51 (11.8%)		0/63 (0%)
Hepatitis C	5/51 (9.8%)		0/63 (0%)
Tooth abscess	5/51 (9.8%)		0/63 (0%)
Respiratory tract infection viral	4/51 (7.8%)		0/63 (0%)
Urinary tract infection	4/51 (7.8%)		7/63 (11.1%)
Catheter related infection	3/51 (5.9%)		0/63 (0%)
Nasopharyngitis	1/51 (2%)		13/63 (20.6%)
Influenza	0/51 (0%)		9/63 (14.3%)
Lower respiratory tract infection	0/51 (0%)		5/63 (7.9%)
Injury, poisoning and procedural complications
Procedural hypertension	9/51 (17.6%)		0/63 (0%)
Arteriovenous fistula site complication	7/51 (13.7%)		1/63 (1.6%)
Arteriovenous fistula site haemorrhage	6/51 (11.8%)		0/63 (0%)
Arteriovenous fistula thrombosis	6/51 (11.8%)		2/63 (3.2%)
Procedural hypotension	4/51 (7.8%)		1/63 (1.6%)
Arteriovenous fistula site haematoma	3/51 (5.9%)		0/63 (0%)
Procedural headache	3/51 (5.9%)		0/63 (0%)
Contusion	2/51 (3.9%)		4/63 (6.3%)
Fall	0/51 (0%)		4/63 (6.3%)
Investigations
Blood pressure increased	6/51 (11.8%)		3/63 (4.8%)
Metabolism and nutrition disorders
Hypokalaemia	3/51 (5.9%)		0/63 (0%)
Hypoglycaemia	2/51 (3.9%)		4/63 (6.3%)
Gout	0/51 (0%)		5/63 (7.9%)
Hyperphosphataemia	0/51 (0%)		4/63 (6.3%)
Musculoskeletal and connective tissue disorders
Muscle spasms	22/51 (43.1%)		3/63 (4.8%)
Arthralgia	6/51 (11.8%)		6/63 (9.5%)
Back pain	4/51 (7.8%)		7/63 (11.1%)
Bone pain	4/51 (7.8%)		2/63 (3.2%)
Pain in extremity	3/51 (5.9%)		5/63 (7.9%)
Nervous system disorders
Headache	28/51 (54.9%)		5/63 (7.9%)
Dizziness	3/51 (5.9%)		5/63 (7.9%)
Psychiatric disorders
Insomnia	4/51 (7.8%)		3/63 (4.8%)
Renal and urinary disorders
Renal failure	0/51 (0%)		5/63 (7.9%)
Respiratory, thoracic and mediastinal disorders
Cough	6/51 (11.8%)		4/63 (6.3%)
Epistaxis	4/51 (7.8%)		1/63 (1.6%)
Interstitial lung disease	4/51 (7.8%)		0/63 (0%)
Dyspnoea	1/51 (2%)		6/63 (9.5%)
Pharyngolaryngeal pain	0/51 (0%)		4/63 (6.3%)
Skin and subcutaneous tissue disorders
Hyperhidrosis	11/51 (21.6%)		0/63 (0%)
Pruritus	5/51 (9.8%)		6/63 (9.5%)
Vascular disorders
Hypertensive crisis	19/51 (37.3%)		0/63 (0%)
Hypotension	19/51 (37.3%)		4/63 (6.3%)
Hypertension	4/51 (7.8%)		13/63 (20.6%)

Limitations/Caveats

Early termination of study due to generation of controlled long-term data in Phase 3 studies. Amended dosing guidelines during the trial to reflect label changes for ESAs; the primary outcome was assessed after the dosing guideline change.

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.