A Study of Once Monthly Subcutaneous Mircera in Dialysis Patients With Chronic Renal Anemia

Study Overview
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Brief Summary
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This single arm study will assess the efficacy, safety and tolerability of once monthly administration of subcutaneous Mircera for the maintenance of hemoglobin levels in dialysis patients with chronic renal anemia. Patients will receive subcutaneous Mircera at a starting dose of 120, 200 or 360 micrograms every 4 weeks, calculated from the last weekly dose of epoetin or darbepoetin alfa previously administered. Subsequent doses will be adjusted to maintain hemoglobin levels within the target range. Treatment duration is 56 weeks, and the target sample size is 200 individuals.

Official Title
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A Single Arm, Open Label Study to Assess the Efficacy, Safety and Tolerability of Once- Monthly Administration of Subcutaneous CERA for the Maintenance of Haemoglobin Levels in Dialysis Patients With Chronic Renal Anemia

Conditions
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Anemia

Intervention / Treatment
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* 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; regular long-term hemodialysis or peritoneal dialysis, with same mode of dialysis for >=3 months; continuous iv maintenance epoetin alfa therapy with same dosing interval during previous 2 months. Exclusion Criteria: transfusion of red blood cells during previous 2 months; poorly controlled hypertension; significant acute or chronic bleeding; active malignant disease (except non-melanoma skin cancer).

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C.E.R.A.<br>Eligible participants will be administered continuous erythropoietin receptor activator (C.E.R.A.[Mircera]) intravenously (IV) every 4 weeks for 44 weeks. The starting dose of 120, 200, or 360 micrograms (mcg) will be based on the dose of epoetin alfa or beta administered in the week preceding the switch to C.E.R.A. Subsequent doses will be adjusted to maintain the individual participant's hemoglobin (Hb) within a range of +/- 1.0 grams per deciliter (g/dL) of the reference hemoglobin (Hb) concentration and between 10.50 and 12.50 g/dL. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Subcutaneous injection every 4 weeks (starting dose of 120, 200 or 360 micrograms, based on previous ESA therapy)<br>* Other names: C.E.R.A.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Maintaining Mean Hemoglobin Concentration Within +/- 1 g/dL of Their Reference Hb and Between 10.5 and 12.5 g/dL During Efficacy Evaluation Period | The percentage of participants who maintained their mean Hb concentration within +/- 1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the Efficacy Evaluation Period (EEP) is reported. The EEP was from Week 17 to Week 24. The reference Hb was calculated from the mean of Hb concentrations based upon the Hb assessments at Weeks -4, -3, -2, -1, and 0. | EEP (Week 17 to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin Concentration Between Reference (Stability Verification Period) and the Efficacy Evaluation Period | Mean change in Hb concentration between reference SVP and the EEP is reported. The SVP was at Weeks -3, -2, -1, and EEP was from Week 17 to Week 24. Participants received epoetin alfa or beta during SVP. | SVP (Weeks -3, -2, -1) and EEP (Week 17 to Week 24) | 
| Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.5-12.5 g/dL Throughout the EEP | Percentage of participants maintaining Hb concentration within the range of 10.5-12.5 g/dL throughout the EEP is reported. The EEP was from Week 17 to Week 24. | EEP (Week 17 to Week 24) | 
| Mean Time Spent By Participants With Hemoglobin Range of 10.5-12.5 g/dL During the EEP | Mean time spent by participants in Hb range of 10.5-12.5 g/dL during the EEP is reported. The EEP was from Week 17 to Week 24. | EEP (Week 17 to Week 24) | 
| Number of Participants With Any Adverse Events or Serious Adverse Events | An adverse event (AE) is untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAEs) is with any of the following outcomes: Death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, and congenital anomaly. | Up to Week 52 | 
| Percentage of Participants Requiring Any Dose Adjustment During DTP and EEP | Percentage of participants requiring any dose adjustment during DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24) is reported. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either > or = 13 g/dL or < or = 9 g/dL; if the difference of 2 consecutive Hb concentrations was > or =2 g/dL; if the values of scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of range of 10.5 to 11.5 g/dL, the difference between the reference value (mean of Hb concentrations based on the Hb assessments at Weeks -4, -3, -2, -1, and 0) and the most recent value was >1 g/dL; if the values of the scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of the range 10 to 12 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted. | DTP (Week 1 to Week 16) and EEP (Week 17 to Week 24) | 
| Incidences of Red Blood Cell Transfusions During the C.E.R.A. Treatment Phase | Red Blood Cells (RBCs) transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP, EEP, and during the long term safety period (LTSP) were reported. | Up to Week 52 | 
| Mean Hemoglobin Levels Over Time | The Hb levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Hematocrit Levels Over Time | The hematocrit (HCT) levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Albumin Levels Over Time | The albumin levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean White Blood Cells and Thrombocytes Over Time | The white blood cells (WBCs) and thrombocyte levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Phosphate and Potassium Levels Over Time | The phosphate and potassium levels were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Creatinine, Iron, and Total Iron Binding Capacity Levels Over Time | The mean creatinine, iron, and total iron binding capacity (TIBC) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean C-Reactive Protein Levels Over Time | The mean C-Reactive Protein (CRP) Levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Ferritin Levels Over Time | The mean ferritin levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Transferrin Saturation Levels Over Time | The mean transferrin saturation (TSAT) levels over time were recorded for each participant at enrolment and at different time points during the study up to Week 48. | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Pulse Rate Over Time | Mean change in pulse rate was defined as the difference between mean pulse rate at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48). | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Blood Pressure Over Time | Mean change in blood pressure (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) before and after dialysis was defined as the difference between mean blood pressure at Baseline and following visits (Weeks 8, 16, 24, 32, 40, and 48). | Baseline (Week 0) and Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Weight Over Time | Mean change in weight was defined as the difference between mean weight at Baseline and following visits (Week 16 and Week 48). | Week 16 and Week 48 |