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.

Study Overview
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Brief Summary
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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.

Official Title
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An Open-Label, Single-Arm, Multicenter Study to Ascertain the Optimal Starting Dose of MIRCERA® Given Subcutaneously for the Maintenance Treatment of Anemia in Pediatric Patients With Chronic Kidney Disease on Dialysis or Not Yet on Dialysis.

Conditions
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Anemia, Renal Insufficiency, Chronic

Intervention / Treatment
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* Drug: Mircera


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mircera<br>Mircera will be administered subcutaneously once every 4 weeks | Drug: Mircera<br>* 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.<br>* Other names: Methoxy polyethylene glycol-epoetin beta;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin (Hb) Concentration Between the Baseline and the Evaluation Period for Each Patient | The Hb change from baseline was calculated on a per-participant basis using an individual's average for both the baseline and evaluation periods and taking the difference. The baseline period was defined as the time between the day of first study dose and the previous 35 days. The evaluation period was defined as the period between Week 17 and Week 21, inclusive. | Baseline up to Week 21 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Average Hb Concentration During the Evaluation Period Within ± 1 g/dL of Their Baseline Hb and Above, Within or Below the Range of 10-12 g/dL | Number of participants with an average Hb concentration during the evaluation period within ± 1 g/dL of their baseline Hb is reported as well as the number of participants with an average Hb concentration above, within or below the range of 10-12 g/dL. The evaluation period was defined as the period between Week 17 and Week 21 inclusive. | Week 17 up to Week 21 | 
| Mean Hb Values and Change From Baseline | The mean Hb concentration over time and the mean change in Hb from baseline over time are presented. | Baseline, Weeks 3, 5, 9, 13, 17, 19, 21, 25, 29, 33, 37, 41, 45 | 
| Change in Mircera Dose Over Time | A dose change was defined as a change in the administered dose strength compared to the preceding dose. | Week 1 to Week 17 | 
| Ratio of Mircera Starting Dose (Week 1) to the Dose at Week 17 | The ratio of Mircera dose was calculated as the median (min-max) ratio of starting dose (Week 1) to the dose at Week 17. Participants who withdrew before Week 17 or who were not administered a Mircera dose at Week 17 visit due to the applicable dose adjustment rules were excluded from the ratio computation. | Week 1, Week 17 | 
| Number of Participants With Adverse Events by Severity as Assessed by Highest World Health Organization (WHO) Toxicity Grade | An adverse event is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease, or exacerbation of existing disease (a worsening in the character, frequency, or severity of a known condition), recurrence of an intermittent medical condition or any deterioration in a laboratory value or other clinical test. | Baseline up to Week 45 | 
| Bioavailability (F) of Mircera in Pediatric Participants Based on Population PK Model | Bioavailability (F) is defined as the percentage of the administered drug, that reaches the systemic circulation. A population PK model was developed for Mircera that adequately describes pediatric data: a 1-compartment model with first order absorption and elimination processes. The bioavailability (F) was estimated using all the data points listed under time frame using the population PK model. | Pre-dose at Week 1, 9, 17; Post-dose at Week 3, Week 19 and additional sample taken between 24 hours and 5 days at participant's convenience |