Peginesatide for Maintenance Treatment of Anemia in Participants on Hemodialysis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Affymax
ClinicalTrials.gov Identifier:
NCT00434330
First received: February 12, 2007
Last updated: June 22, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Anemia
Chronic Kidney Disease
Chronic Renal Failure
Drug: peginesatide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Affymax:

Primary Outcome Measures:
  • Mean Hemoglobin Throughout the Trial and Mean Hemoglobin Change From Baseline Throughout the Trial. [ Time Frame: Baseline and Weeks 2-29 ] [ Designated as safety issue: No ]
    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.


Enrollment: 91
Study Start Date: December 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00434330

Locations
Bulgaria
Research Facility
Burgas, Bulgaria, 8000
Research Facility
Pleven, Bulgaria, 5800
Research Facility
Plovdiv, Bulgaria, 4003
Research Facility
Rousse, Bulgaria, 7002
Research Facility
Sofia, Bulgaria, 1606
Research Facility
Sofia, Bulgaria, 1527
Research Facility
Sofia, Bulgaria, 1709
Research Facility
Varna, Bulgaria, 9010
Research Facility
Veliko Tarnovo, Bulgaria, 5000
Romania
Research Facility
Arad, Romania, 310017
Research Facility
Bacau, Romania, 600114
Research Facility
Bucuresti, Romania
Research Facility
Iasi, Romania, 700503
Research Facility
Timisoara, Romania, 300736
United Kingdom
Research Facility
London, United Kingdom, SE5 9RS
Sponsors and Collaborators
Affymax
Investigators
Study Director: Vice President, Clinical Development Affymax, Inc.
  More Information

No publications provided

Responsible Party: Affymax
ClinicalTrials.gov Identifier: NCT00434330     History of Changes
Other Study ID Numbers: AFX01-07, 2006-002815-28
Study First Received: February 12, 2007
Results First Received: April 26, 2012
Last Updated: June 22, 2012
Health Authority: Romania: National Medicines Agency
Romania: Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee
Bulgaria: Bulgarian Drug Agency
Bulgaria: Ethics committee

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
Anemia
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Failure, Chronic
Urologic Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on September 22, 2014