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

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

Official Title
-----------------
A Randomized, Controlled, Open-Label, Multi- Center, Parallel-Group Study to Demonstrate the Efficacy and Safety of RO0503821 When Administered Subcutaneously for the Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease Who Are on Dialysis

Conditions
-----------------
Anemia

Intervention / Treatment
-----------------
* Drug: epoetin alfa or beta
* Drug: methoxy polyethylene glycol-epoetin beta (Mircera)
* Drug: methoxy polyethylene glycol-epoetin beta (Mircera)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patients >=18 years of age; chronic renal anemia; on dialysis therapy for at least 12 weeks before screening; receiving sc 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
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin Concentration From Baseline to Evaluation Periods | A time adjusted mean change in hemoglobin (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 value from the average evaluation period Hb value. All blood samples for Hb measurements were taken prior to study drug administration. Analysis used last observation carried forward (LOCF) for missing Hb values to correct for the impact of early dropouts. The baseline period is defined as Week -4 to Week -1. The evaluation period is 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 Hb Concentration During the Evaluation Period Within +-1 g/dL of Their Average Baseline Hb Concentration | All mean Hb values recorded during the evaluation period were calculated and subtracted from the mean baseline Hb value for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline hemoglobin concentration is given. The evaluation period is defined as Week 29 to Week 36. | Evaluation period (Week 29 to Week 36) | 
| Number of Participants With Red Blood Cell Transfusions | The number of participants who received RBC transfusions were reported. | Up to Week 36 | 
| Number of Participants With Any Adverse Events, Any Serious Adverse Events, and Deaths | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | Up to week 52 | 
| 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/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 millimoles per liter [mmol/L]), potassium (2.9 - 5.8 mmol/L), glucose (2.80 - 11.10 mmol/L). | Up to week 52 | 
| Change From Baseline in Systolic and Diastolic Blood Pressure - at Weeks 36 and 52 in Hemodialysis Participants | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in sitting position before and after dialysis session in haemodialysis participants. | From Baseline (Week -4 to Week -1) to Week 36 and Week 52 | 
| Change From Baseline in Pulse Rate at Weeks 36 and 52 in Hemodialysis Participants | Pulse rate in beats per minute (BpM) was measured at each study visit, i.e., once a week during the dose titration and evaluation periods, once every two weeks during the long-term safety observation period and at the final visit. It was measured before blood sampling and RO0503821/epoetin administration and before the dialysis session in haemodialysis participants. | From Baseline (Week -4 to Week -1) to Week 36 and Week 52 | 
| Change From Baseline in Systolic and Diastolic Blood Pressure at Weeks 36 and 52 in Peritoneal Dialysis Participants | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured in sitting position before and after dialysis session in peritoneal dialysis participants. | From Baseline (Week -4 to Week -1) to Week 36 and Week 52 | 
| Change From Baseline in Pulse Rate - Peritoneal Dialysis Participants | Pulse rate in BpM was measured at each study visit, i.e., once a week during the dose titration and evaluation periods, once every two weeks during the long-term safety observation period and at the final visit. It was measured before blood sampling and RO0503821/epoetin administration and before the dialysis session in peritoneal dialysis participants. | From Baseline (Week -4 to Week -1) to Week 36 and Week 52 |