Peginesatide for Maintenance Treatment of Anemia in Participants on Hemodialysis
Condition: Anemia; Chronic Kidney Disease; Chronic Renal Failure
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic; Anemia
Intervention: peginesatide; peginesatide; peginesatide; peginesatide; peginesatide; peginesatide
Intervention description: 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.; 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.; 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.; 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.; 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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).
    

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