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 Mircera, given as maintenance treatment for renal anemia in chronic kidney disease patients on dialysis who were previously receiving iv epoetin. 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: Epoetin alfa or beta
* Drug: RO0503821 (1x/2 Weeks)
* Drug: RO0503821 (1x/4 Weeks)


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 IV epoetin 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>Participants received RO0503821 (Mircera [methoxy polyethylene glycol-epoetin beta]) once every two weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (60, 100, or 180 microgram [mcg]) that was based on the Epoetin dose (<8000, 8000-16000, >16000 International units [IU]/Week) administered during the week preceding the switch to the study drug. | Drug: RO0503821 (1x/2 Weeks)<br>* 60, 100, or 180 microgram (mcg) (starting dose) once every two weeks intravenously for 52 weeks.<br>* Other names: Mircera;|
| Experimental: RO0503821 (1x/4 Weeks)<br>Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (120, 200, or 360 mcg) that was based on the Epoetin dose (<8000, 8000-16000, >16000 IU/Week) administered during the week preceding the switch to the study drug. | Drug: RO0503821 (1x/4 Weeks)<br>* 120, 200 or 360 mcg (starting dose) once every four weeks intravenously for 52 weeks.<br>* Other names: Mircera;|
| Active Comparator: Epoetin (1-3x/Weeks)<br>Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks. | Drug: Epoetin alfa or beta<br>* intravenously 3 times weekly for 52 weeks, as prescribed<br>* Other names: Epoetin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period | A time adjusted mean change in Hb concentration was calculated using an Area Under the Curve (AUC) approach, for both periods separately. Change in Hb concentration between the Baseline and evaluation periods was calculated by subtracting the calculated average baseline Hb from the average evaluation period Hb. At the end of the Week 36, data allowing the evaluation of the therapeutic response was available for 188 out of 221 eligible participants in RO0503821 (1x/2 Weeks) arm; 172 out of 220 eligible participants in RO0503821 (1x/4 Weeks); and 180 out of 225 participants in Epoetin (1-3x/Weeks) arm. | Baseline, Week 29 to Week 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration. | The mean Hb of all values recorded during the evaluation period were calculated, and were subtracted from the mean baseline Hb for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline hemoglobin concentration is given. | Baseline, Week 29 to Week 36 | 
| The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods | The number of participants who received RBC transfusions during the titration and evaluation periods were reported . | Week 1 to Week 36 | 
| Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) | Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for Platelet was 100-550x10^9/Litre [L], for WBC was 3.0-18.0.0x10^9/L, and for RBC was 3.80-6.10x10^12/L. | Up to Week 53 | 
| Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes | Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for aspartate aminotransferase (AST) was 0-80 (unit per litre [U/L]), alanine aminotransferase (ALT) 0-110 U/L, alkaline phosphatase (ALP) 0-220 U/L, albumin >=30.0 gram/litre (g/L), glucose in non-diabetics 2.80-11.10 (millimol/litre [mmol/L]); potassium 2.90-5.80 mmol/L, and phosphorus 0.75-1.60 mmol/L | Up to Week 53 | 
| Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 | Blood pressure was measured by manual assessment or automated reading throughout the entire 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 (SBP) and diastolic (DBP) 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 value and a value for specified time period. | Baseline, Week 36 and Week 52 | 
| Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death | An 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. An 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. | Upto Week 53 |