Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis

Study Overview
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Brief Summary
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This sequential study will assess the efficacy and safety of multiple doses of intravenous (IV) methoxy polyethylene glycol-epoetin beta (MIRCERA), and will determine the optimum starting dose for maintenance treatment of anemia in children with chronic kidney disease on hemodialysis. Pediatric participants will remain on epoetin alfa, epoetin beta or darbepoetin alfa during the screening period, after which they will receive IV MIRCERA monthly, at a starting dose related to the previous weekly epoetin or darbepoetin alfa dose. Depending on the response achieved, another group may be selected to receive a higher or a lower dose.

Official Title
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An Open-Label Multi-center, Multiple Dose Study to Determine the Optimum Starting Dose of Intravenous MIRCERA for Maintenance Treatment of Anemia in Pediatric Participants With Chronic Kidney Disease on Hemodialysis

Conditions
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Renal Anemia

Intervention / Treatment
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* Drug: Methoxy Polyethylene Glycol-Epoetin Beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 5-17 years (in Russia only: 12-17 years) with clinically stable chronic renal anemia Hemodialysis for greater than or equal to (>=) 8 weeks Intravenous stable maintenance treatment with epoetin alfa, epoetin beta, or darbepoetin alfa for >= 8 weeks before screening and with no weekly dose change >= 25 percent (%) (increase or decrease) during the 2 weeks of screening Exclusion Criteria: Overt gastrointestinal bleeding within 8 weeks before screening or during the screening period Red blood cell (RBC) transfusions within 8 weeks before screening or during the screening period Active malignant disease Pure red cell aplasia (PRCA) or history of PRCA Pregnant or lactating females Sexually active participants: not willing to use reliable contraception during treatment and for 90 days following the end of treatment

Ages Eligible for Study
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Minimum Age: 5 Years
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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIRCERA Group 1: Intermediate-Conversion-Factor Group<br>Participants will receive methoxy polyethylene glycol-epoetin beta (MIRCERA) IV injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-stimulating Agent (ESA) dose (4 * previous weekly epoetin dose [international units {IU}]/250 or 4 * previous weekly darbepoetin alfa dose [micrograms {mcg}]/1.1) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks. | Drug: Methoxy Polyethylene Glycol-Epoetin Beta<br>* Will be administered IV, every 4 weeks.<br>* Other names: RO0503821;|
| Experimental: MIRCERA Group 2: High-Conversion-Factor Group<br>Participants will receive MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 * previous weekly epoetin dose [IU]/125 or 4 * previous weekly darbepoetin alfa dose [mcg]/0.55) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with Hb within ± 1 g/dL of their baseline Hb and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks. | Drug: Methoxy Polyethylene Glycol-Epoetin Beta<br>* Will be administered IV, every 4 weeks.<br>* Other names: RO0503821;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Average Hb Concentration Between Baseline and Evaluation Period | A time adjusted average baseline Hb concentration for each individual was calculated using an area under the curve (AUC) approach from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Week 17 to Week 21). The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb concentration from the evaluation period Hb concentration. | Baseline (Day -20 to Day 1), Evaluation Period (Week 17 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 | Baseline Hb value was defined as the average Hb concentration from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21). | Evaluation Period (Week 17 to Week 21) | 
| Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL | The evaluation period Hb concentration was defined as the average Hb concentration from all available Hb measurements taken during the evaluation period (Week 17 to Week 21). | Evaluation Period (Week 17 to Week 21) | 
| Number of Participants With Blood Transfusions |  | Baseline to Week 20 | 
| Change in Average Reticulocyte Count Between the Baseline and Evaluation Period | A time adjusted average baseline reticulocyte count for each individual was calculated using an AUC approach from all available reticulocyte counts taken during the baseline period (Day -20 to Day 1). The average evaluation period reticulocyte count for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Weeks 17 to 21). The change in reticulocyte count between the baseline and evaluation periods was calculated by subtracting the baseline reticulocyte count from the evaluation period reticulocyte count. Relative reticulocytes were recorded conversion to absolute values was performed. | Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21) | 
| Maximum Observed Serum Concentration (Cmax) of MIRCERA | Cmax was defined as the highest serum concentration observed from all sample collection timepoints (as provided in timeframe) and was averaged out among participants and reported. | Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13 | 
| Area Under the Serum Concentration-Time Curve From 0 to 672 Hours (AUC0-672h) of MIRCERA | Area under the serum concentration versus time curve over 672 hours. AUC0-672h represents area under the serum concentration versus time curve from time zero to end of dosing interval (AUC0-tau). | Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13 | 
| Time to Reach Cmax (Tmax) of MIRCERA | Tmax was defined as the time (in hours) to achieve Cmax (Cmax was defined as the highest serum concentration observed over all sample collection timepoints [as provided in timeframe]). The median time, among all participants, was reported. | Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13 | 
| Apparent Terminal Phase Half-Life (t1/2) of MIRCERA | t1/2 was defined as the time (in hours) measured (from all sample collection timepoints [as provided in timeframe]) for the serum concentration to decrease by one half. The t1/2 was calculated as natural logarithm of 2 divided by λz; where λz = terminal elimination rate constant. | Pre-dose (with 1 hour before drug administration) and 2, 48 hours post dose on Week 9, at Weeks 10, 11, and 12, pre-dose (with 1 hour before drug administration) on Week 13 |