Ascertain the Optimal Starting Dose of Mircera Given Subcutaneously for Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.
Condition: Anemia; Renal Insufficiency, Chronic
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Anemia
Intervention: Mircera
Intervention description: The initial dose of Mircera will be one of nine starting doses corresponding to the prefilled syringe strengths based on the total weekly erythropoiesis-stimulating agent (ESA) dose during the screening period.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 3 Months
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      Ascertain the starting dose of Mircera given subcutaneously for the maintenance treatment of
      anemia in pediatric participants with chronic kidney disease (CKD) on dialysis or not yet on
      dialysis when switching from stable subcutaneous (SC) maintenance treatment with epoetin
      alfa, epoetin beta, or darbepoetin alfa.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pediatric participants 3 months to 17 years of age with clinically stable chronic
             renal anemia

          -  CKD with estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73 m2
             (determined by the Bedside Schwartz formula) or dialysis treatment for at least 8
             weeks before the first dose of Mircera

          -  For participants on peritoneal dialysis (PD): a weekly Kt/V≥ 1.8

          -  For participants on hemodialysis (HD): adequate HD, urea reduction ratio (URR) > 65%
             or Kt/V > 1.2 for participants on HD three times per week.

        Participants with fewer than or more than three HD sessions per week should have a weekly
        Kt/V≥ 3.6.

          -  Baseline Hb concentration 10.0-12.0 g/dL determined from the mean of two Hb values
             measured at Visit 1 (Week -3) and Visit 2 (Week -1)

          -  Stable SC maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa
             with the same dosing interval for at least 6 weeks before the first dose of Mircera

          -  Stable dose of epoetin alfa, epoetin beta, or darbepoetin alfa treatment with no
             weekly dose change > 25% (increase or decrease) for at least 4 weeks before the first
             dose of Mircera

          -  Adequate iron status defined as ferritin≥100 ng/mL or transferrin saturation (TSAT)≥
             20% (or percentage of hypochromic red cells < 10%); mean of two values measured during
             screening.

        Exclusion Criteria:

          -  Overt gastrointestinal bleeding within 8 weeks before screening or during the
             screening period

          -  RBC transfusions within 8 weeks before screening or during the screening period

          -  Hemoglobinopathies (e.g., homozygous sickle-cell disease, thalassemia of all types)
             Hemolytic anemia, Active malignant disease

          -  PD subjects with an episode of peritonitis within the past 30 days prior to screening
             and/or during the screening period

          -  Uncontrolled or symptomatic inflammatory disease (e.g., systemic lupus erythematosus)

          -  Uncontrolled hypertension as assessed by the investigator

          -  Epileptic seizures within 3 months prior to screening and during the screening period

          -  Administration of any investigational drug within 4 weeks prior to screening or
             planned during the study

          -  Severe hyperparathyroidism (intact parathyroid hormone [PTH]≥ 1000 pg/mL or whole PTH≥
             500 pg/mL) or biopsy-proven bone marrow fibrosis

          -  Kidney transplant with use of immunosuppressive therapies known to exacerbate anemia

          -  Known hypersensitivity to recombinant human erythropoietin (EPO), polyethylene glycol,
             or any constituent of the study drug formulation

          -  Anti-EPO antibody (AEAB)-mediated pure red cell aplasia (PRCA) or history of AEAB
             mediated PRCA or positive AEAB test result in the absence of PRCA

          -  High likelihood of early withdrawal or interruption of the study (e.g., planned living
             donor kidney transplant within 5 months of study start)

          -  Planned elective surgery during the entire study period