Clinical trial NCT00434330: Peginesatide for Maintenance Treatment of Anemia in Participants on Hemodialysis
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia
Chronic Kidney Disease
Chronic Renal Failure
Keywords: 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
Lead sponsor: Affymax
Sponsor class: INDUSTRY
First posted: 2007-02-13
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 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

Primary outcomes:
measure: Mean Hemoglobin Throughout the Trial and Mean Hemoglobin Change From Baseline Throughout the Trial.
timeFrame: Baseline and Weeks 2-29
Secondary outcomes:
Other outcomes:
measure: 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)
timeFrame: Weeks 2 to 29
measure: Proportion of Participants Who Maintained Hemoglobin Within 10 to 12.5 g/dL Throughout the Trial
timeFrame: Weeks 2 to 29
measure: Proportion of Participants Who Maintain Hemoglobin Within 9.5 to 13.0 g/dL Throughout the Trial
timeFrame: Weeks 2 to 29
Locations:
city: Burgas
country: Bulgaria
facility: Research Facility
city: Pleven
country: Bulgaria
facility: Research Facility
city: Plovdiv
country: Bulgaria
facility: Research Facility
city: Rousse
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facility
city: Sofia
country: Bulgaria
facility: Research Facility
city: Varna
country: Bulgaria
facility: Research Facility
city: Veliko Tarnovo
country: Bulgaria
facility: Research Facility
city: Arad
country: Romania
facility: Research Facility
city: Bacau
country: Romania
facility: Research Facility
city: Bucuresti
country: Romania
facility: Research Facility
city: Iasi
country: Romania
facility: Research Facility
city: Timisoara
country: Romania
facility: Research Facility
city: London
country: United Kingdom
facility: Research Facility
Study officials:
affiliation: Affymax, Inc.
name: Vice President, Clinical Development
role: STUDY_DIRECTOR
References: