A Study of Subcutaneous Mircera in Patients With Chronic Kidney Disease, Not on Dialysis.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy and safety of Mircera and darbepoetin alfa in the treatment of anemia in patients with chronic kidney disease who are not on dialysis and who are receiving subcutaneous darbepoetin alfa maintenance therapy. Patients will be randomized either to remain on darbepoetin alfa therapy as per local label, or to switch to monthly subcutaneous Mircera, at a starting dose of 120, 200 or 360 micrograms, depending on the weekly dose of darbepoetin alfa administered prior to the first dose of Mircera. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
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An Open-label, Randomized, Multi-center, Parallel Group Non-inferiority Study of Subcutaneous Injections of RO0503821 Given Once Monthly vs. Darbepoetin Alfa Given According to Local Label in Patients With Chronic Kidney Disease Who Are Not on Dialysis.

Conditions
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Anemia

Intervention / Treatment
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* Drug: Mircera
* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; chronic kidney disease, not requiring dialysis; receiving darbepoetin alfa maintenance therapy for >=8 weeks before screening, and during screening/baseline period. Exclusion Criteria: overt gastrointestinal bleeding within 8 weeks before screening, or during screening/baseline period; transfusion of red blood cells within 8 weeks before screening, or during screening/baseline period; active malignant disease; previous treatment with Mircera.

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mircera<br>Participants received Mircera by subcutaneous injection once every month during the dose titration (7 months) and evaluation period (2 months). The starting dose was based on the weekly dose of darbepoetin alfa administered prior to the switch to Mircera, and was either 120, 200 or 360 µg Mircera per month. The dose was then adjusted to maintain Hemoglobin levels within the defined target range and also according to the need for red blood cell transfusions (due to worsening anemia), or for toxicity related to Mircera. | Drug: Mircera<br>* Starting dose of 120, 200 and 360 micrograms administered by subcutaneous injection once a month.<br>* Other names: Methoxy polyethylene glycol-epoetin beta;|
| Active Comparator: Darbepoetin alfa<br>Participants continued to receive the same dose of darbepoetin alfa as before screening by subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling during the dose titration (7 months) and the evaluation period (2 months). | Drug: Darbepoetin alfa<br>* As prescribed, subcutaneous injection once every week, once every 2 weeks or once every month as per local labeling specifications.<br>* Other names: Aranesp®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin (Hb) Concentration From Baseline to the Evaluation Period | A time adjusted average baseline hemoglobin (Hb) concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the two month evaluation period. The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration. | Baseline (measurements at Week -4, Week -2 and Day 1) and Evaluation Period (Months 8 and 9; measurements twice a month and at the final visit). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin Concentration From Baseline Over Time |  | From Baseline to 9 months; blood samples for hemoglobin measurements were taken twice a month, at each study visit. | 
| Number of Participants With Red Blood Cell (RBC) Transfusions | Red blood cell (RBC) transfusions could be given during the treatment period in case of medical need, i.e., in severely anemic patients with recognized symptoms or signs of anemia (e.g., in patients with acute blood loss, with severe angina, or whose Hemoglobin decreased to critical levels). The number of participants who had at least one red blood cell transfusion during the entire study, during the Titration Period and during the Evaluation Period is presented. Participants who received more than one transfusion within a defined period are only counted once. | From randomization to Month 9 | 
| Participants With Adverse Events | Adverse events were collected during the treatment period (from the first treatment dose) up to 30 days after last dose or at least until the date of last contact if the date of last contact occurred after the specified 30 day period. | Randomization to Month 10 (final visit) |