A Study of Mircera for the Maintenance Treatment of Anemia in Dialysis Patients

Study Overview
=================
Brief Summary
-----------------
This 2 arm study will compare the efficacy and safety of Mircera and darbepoetin alfa, administered at extended dosing intervals, in the maintenance treatment of anemia in patients with chronic kidney disease (CKD) who are on hemodialysis. Eligible patients receiving once-weekly intravenous (IV) darbepoetin alfa maintenance treatment will be randomized to receive either intravenous Mircera once a month (at a starting dose of 120, 200 or 360 micrograms/month, depending on the weekly dose of darbepoetin alfa prior to start of study) or intravenous darbepoetin alfa every 2 weeks before switching to once monthly administration. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.

Official Title
-----------------
A Randomized, Controlled, Open Label, Multicenter, Parallel-group Study to Compare the Effect of Mircera With That of Darbepoetin Alfa, Administered Intravenously at Extended Dosing Intervals, for the Maintenance Treatment of Anemia in Patients With Chronic Kidney Disease Who Are on Hemodialysis

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: adult patients, >=18 years of age; chronic renal anemia; hemodialysis 3 times weekly for >=12 weeks before screening, and during screening/baseline period; 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 malignancy;

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: MIRCERA<br>Eligible participants with anemia in CKD who were on hemodialysis will receive methoxy polyethylene glycol-epoetin beta (MIRCERA [RO0503821]) IV once every month up to 52 weeks. The starting dose of MIRCERA which will be administered during the treatment period will depend on the dose of darbepoetin alfa administered during screening period i.e., 120, 200 and 360 mcg for weekly darbepoetin alfa doses of <40, 40-80, and >80 mcg, respectively. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* 120, 200 or 360 micrograms iv / month, starting dose<br>|
| Active Comparator: Darbepoetin Alfa<br>Eligible participants with anemia in CKD who were on hemodialysis will receive darbepoetin alfa (Aranesp) IV once every two weeks up to 26 weeks and darbepoetin alfa IV twice the dose than earlier, once every month from Week 27 up to Week 52. | Drug: Darbepoetin alfa<br>* As prescribed, iv.<br>* Other names: Aranesp;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Lesser Than or Equal to One Gram Per Deciliter Decrease in Average Hemoglobin From Baseline and Maintaining Average Hemoglobin Level Greater Than or Equal to 10.5 g/dL Over Evaluation Period | Randomized participants with an average hemoglobin (Hb) decrease from Baseline (Week -4 to Week -1) not exceeding 1.0 gram per deciliter (g/dL) and an absolute average Hb >= 10.5 g/dL during the evaluation period (Weeks 50-53) were defined as responders. Non-responders included participants without any Hb data during the second treatment period and those who did not meet the response criteria and thus were not included in the analysis. | Baseline (Week -4 to Week -1) and Evaluation period (Weeks 50 to 53) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percentage Change in MIRCERA and Darbepoetin Alpha Dose Over Time | All participants received once monthly treatment schedule of both MIRCERA and darbepoetin alpha for the respective treatment arms after Week 27 and these analyses are based on the absolute doses. The average dose in Months 11 and 12 was defined as the mean of all administered doses between study Days 302 and 363. The change in dose was calculated as the percentage change between the respective dose at Week 27 and the average corresponding dose during Months 11 and 12 in each treatment group. | Week 27 to Month 12 | 
| Number of Participants With Marked Laboratory Abnormality Over Time | Values of laboratory parameters higher (H) or lower (L) than the Roche defined reference range were considered as abnormality. The laboratory parameters with abnormality were platelets, white blood cells (WBC), albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and potassium. Blood samples were drawn before drug administration and before the dialysis session. | Up to Week 53 | 
| Median Blood Pressure Over Time | Systolic and diastolic blood pressures (BP) were measured before and after the dialysis session at every week from Baseline (Week -4 to Week -1) to Week 53. Median pre-dialysis diastolic blood pressure (PrD DBP) , median post-dialysis diastolic blood pressure (PoD DBP), median pre-dialysis systolic blood pressure (PrD SBP), and post-dialysis systolic blood pressure (PoD SBP) were reported at Baseline (Week -4 to Week -1) , Week 28 and Week 52. | Baseline (Week -4 to Week -1), Week 28, and Week 52 | 
| Mean Pulse Rate Over Time | Pulse rate is defined as the number of heartbeats in a minute and was assessed in sitting position of the participants at every week from Baseline (Week -4 to Week -1) to Week 53. Summary data of mean values of pulse rate are presented at Baseline (Week -4 to Week -1), Week 28 and Week 52. | Baseline (Week -4 to Week -1), Week 28, and Week 52 | 
| Number of Participants With Any Adverse Events, Serious Adverse Events, and Deaths | An adverse event (AE) can be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. A serious adverse event (SAE) is any adverse event that can result in death or is life-threatening or required in participants hospitalization or prolongation of existing hospitalization or results in persistent or significant disability/incapacity; or is a congenital anomaly/birth defect; or is medically significant or requires intervention to prevent one or other of the outcomes listed above. SAEs were reported up to Week 56, while nonserious AEs up to Week 52. | From screening to Week 56 |