Peginesatide for Maintenance Treatment of Anemia in Participants on Hemodialysis

Anemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00434330
• Other study ID #: AFX01-07
• Secondary ID: 2006-002815-28
• Status: Completed
• Phase: Phase 2
• First received: February 12, 2007
• Last updated: June 22, 2012
• Start date: December 2006
• Est. completion date: April 2008

Study information

• Verified date: June 2012
• Source: Affymax
• Contact: n/a
• Is FDA regulated: No
• Health authority: Romania: National Medicines AgencyRomania: Ethics CommitteeUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: Research Ethics CommitteeBulgaria: Bulgarian Drug AgencyBulgaria: Ethics committee
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 91
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Chronic Kidney Disease
• Chronic Renal Failure
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

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.
• 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.
• 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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Bulgaria	Research Facility	Burgas
Bulgaria	Research Facility	Pleven
Bulgaria	Research Facility	Plovdiv
Bulgaria	Research Facility	Rousse
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Sofia
Bulgaria	Research Facility	Varna
Bulgaria	Research Facility	Veliko Tarnovo
Romania	Research Facility	Arad
Romania	Research Facility	Bacau
Romania	Research Facility	Bucuresti
Romania	Research Facility	Iasi
Romania	Research Facility	Timisoara
United Kingdom	Research Facility	London

Sponsors (1)

Lead Sponsor	Collaborator
Affymax

Countries where clinical trial is conducted

Bulgaria,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Hemoglobin Throughout the Trial and Mean Hemoglobin Change From Baseline Throughout the Trial.	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.	Baseline and Weeks 2-29	No