Study to Determine Optimum Intravenous Starting Dose of MIRCERA for Treatment of Pediatric Participants With Anemia and Chronic Kidney Disease on Hemodialysis
- Registration Number
- NCT00717366
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MIRCERA Group 1: Intermediate-Conversion-Factor Group Methoxy Polyethylene Glycol-Epoetin Beta 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. MIRCERA Group 2: High-Conversion-Factor Group Methoxy Polyethylene Glycol-Epoetin Beta 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.
- Primary Outcome Measures
Name Time Method Change in Average Hb Concentration Between Baseline and Evaluation Period Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21) 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.
- Secondary Outcome Measures
Name Time Method Number of Participants With Blood Transfusions Baseline to Week 20 Change in Average Reticulocyte Count Between the Baseline and Evaluation Period Baseline (Day -20 to Day 1), Evaluation Period (Week 17 to Week 21) 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.
Maximum Observed Serum Concentration (Cmax) of MIRCERA 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 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.
Area Under the Serum Concentration-Time Curve From 0 to 672 Hours (AUC0-672h) of MIRCERA 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 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).
Time to Reach Cmax (Tmax) of MIRCERA 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 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.
Number of Participants With an Average Hb Concentration During the Evaluation Period Within ±1 g/dL of Their Baseline Hb Evaluation Period (Week 17 to Week 21) 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).
Number of Participants With an Average Hb Concentration During the Evaluation Period Above, Within or Below the Range of 10-12 g/dL Evaluation Period (Week 17 to Week 21) 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).
Apparent Terminal Phase Half-Life (t1/2) of MIRCERA 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 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.
Trial Locations
- Locations (39)
Royal Children'S Hospital; Department of Nephrology
🇦🇺Parkville, Victoria, Australia
Hôpital Enfants Reine Fabiola
🇧🇪Bruxelles, Belgium
UZ Leuven Gasthuisberg
🇧🇪Leuven, Belgium
Hopital Femme Mere Enfant; Ped Nephrologie Rhumatologie
🇫🇷Bron, France
Hopital Jeanne De Flandre; Cons Pediatrie
🇫🇷Lille, France
Hopital Timone Enfants; Nephrologie Hemodialyse
🇫🇷Marseille, France
Hopital Arnaud De Villeneuve; Pediatrie I
🇫🇷Montpellier, France
Hôpital Robert Debré; Nephrologie pediatrique
🇫🇷Paris, France
Hopital Armand Trousseau; Pediatrie Nephrologie
🇫🇷Paris, France
Höpital Hautepierre; Pediatrie 1
🇫🇷Strasbourg, France
Scroll for more (29 remaining)Royal Children'S Hospital; Department of Nephrology🇦🇺Parkville, Victoria, Australia