A Study of Intravenous Mircera for the Treatment of Anemia in Dialysis Patients.

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of intravenous (iv) Mircera given as maintenance treatment for renal anemia in chronic kidney disease patients on dialysis who were previously receiving iv darbepoetin alfa. The anticipated time on study treatment is 1-2 years and the target sample size is 100-500 individuals.

Official Title
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A Randomized, Controlled, Open-label, Multi-center, Parallel-group Study to Demonstrate the Efficacy and Safety of RO0503821 When Administered Intravenously for the Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease Who Are on Dialysis.

Conditions
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Anemia

Intervention / Treatment
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* Drug: Darbepoetin alfa
* Drug: methoxy polyethylene glycol-epoetin beta [Mircera]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients >=18 years of age; chronic renal anemia; on dialysis therapy for at least 12 weeks before screening; receiving darbepoetin alfa iv for at least 8 weeks before screening. Exclusion Criteria: women who are pregnant, breastfeeding or using unreliable birth control methods; administration of another investigational drug within 4 weeks before screening, or during the study period.

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: RO0503821 (1x/2 Weeks)<br>Eligible participants will be administered with RO0503821 ([methoxy polyethylene glycol-epoetin beta] {Mircera}) intravenously (IV), every 2 weeks during Weeks 1 through 52. The starting dose of RO0503821 (60, 100, or 180 micro gram [µg]) was based on the dose of darbepoetin alfa at the time of randomization (< 40, 40 to 80, or > 80 µg per week, respectively). | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* RO0503821 was administered IV, every 2 weeks during Weeks 1 through 52. The starting dose of RO0503821 (60, 100, or 180 micro gram [µg]) was based on the dose of darbepoetin alfa at the time of randomization (< 40, 40 to 80, or > 80 µg per week, respectively).<br>|
| Active Comparator: Darbepoetin (1x/1-2 Weeks)<br>Eligible participants will be administered with darbepoetin alfa IV, every week or every 2 weeks during Weeks 1 through 52. | Drug: Darbepoetin alfa<br>* Darbepoetin alfa was administered IV, every week or every 2 weeks during Weeks 1 through 52.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin Concentration (g/dL) From Baseline to Evaluation Period | A time adjusted mean change in hemoglobin (Hb) concentration was calculated using an area under the curve approach, for both periods separately. Change in Hb concentration between the baseline (Week -4 to Week -1) and evaluation periods was calculated by subtracting the calculated average baseline Hb value from the average evaluation period Hb value. All blood samples for Hb measurements were taken prior to study drug administration. The analysis used the last observation carried forward (LOCF) for missing Hb values for correction of the impact of early drop outs. The baseline period was defined as Week -4 to Week -1. The evaluation period was defined as Week 29 to Week 36. | Baseline (Week -4 to Week -1) and Evaluation Period (Week 29 to Week 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Maintaining Average Hemoglobin Concentration During the Evaluation Period Within +-1 g/dL of Their Average Baseline Hemoglobin Concentration | The average Hb of all values recorded during the evaluation period was calculated, and this average was subtracted from the average baseline Hb values for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline Hb concentration is displayed. The evaluation period was defined as Week 29 to Week 36. | Baseline (Week -4 to Week -1) and Evaluation Period (Week 29 to Week 36) | 
| Number of Participants With Red Blood Cell Transfusions During the Dose Titration and Evaluation Periods | A combined data of the number of participants who received Red Blood Cell (RBC) transfusions during the titration and evaluation periods is reported. A period of 28 weeks after the first dose of the study drug was used for dose titration and stabilization of Hb concentration. The dose titration period was followed by an 8-week evaluation period (weeks 29 to 36). | Week 1 to Week 36 | 
| Number of Participants With Marked Laboratory Abnormalities | A marked abnormality range was defined as above and/or below a value which was considered to be potentially clinically relevant. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the reference range of the following laboratory parameters: White blood cells (WBC) (3.0- 18.0 10^9/liter [L]), platelets (100 - 550 10^9/L), (alanine aminotransferase [(ALAT)] (0 - 110 units per liter [U/L]), alkaline phosphatase (ALP) (0 - 220 U/L), aspartate aminotransferase (ASAT) (0 - 80 U/L), albumin >= 30 g/L, phosphate (0.75 - 1.60 millimole per liter [mmol/L]), potassium (2.9 - 5.8 mmol/L), glucose (2.80 - 11.10 mmol/L). | Up to Week 52 | 
| Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Blood pressure Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) was measured by manual assessment or automated reading throughout the study for every participant. Blood pressure was taken in the sitting position after at least 5 minutes rest. An appropriate -sized cuff was used and both systolic and diastolic blood pressures were recorded before dialysis (BD) and after dialysis (AD). | Baseline, Week 36, and Week 52 | 
| Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 | Change in pulse rate (beats per minute [bpm]) from baseline values includes only those participants with both a baseline (BL) value and a value for specified time period. | Baseline, Week 36, and Week 52 | 
| Number of Participants With Any Adverse Events, Any Serious Adverse Event, and Deaths | An Adverse Event (AE) is defined as 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. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. Overall deaths occurred in the study were reported. | Up to Week 52 |