A Study of Intravenous Mircera in Hemodialysis 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 intravenous Mircera for the maintenance of hemoglobin levels in hemodialysis patients with chronic renal anemia. Patients will receive 4-weekly intravenous injections of Mircera, at a starting dose of 120, 200 or 360 micrograms. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 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 Intravenous C.E.R.A. for the Maintenance of Haemoglobin Levels in Haemodialysis Patients With Chronic Renal Anaemia.

Conditions
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Anemia

Intervention / Treatment
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* Drug: methoxy polyethylene glycol-epoetin beta


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >= 18 years of age; chronic renal anemia; continuous stable iv or sc maintenance epoetin therapy during previous 4 weeks; regular long-term hemodialysis therapy with the same mode of dialysis for previous 3 months. Exclusion Criteria: transfusion of red blood cells during previous 2 months; poorly controlled hypertension requiring hospitalization or interruption of epoetin treatment in previous 6 months; significant acute or chronic bleeding.

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. 120, 200, or 360 mcg<br>Eligible participants were administered Continuous Erythropoietin Receptor Activator (C.E.R.A.) at a dose of 120, 200, or 360 microgram (mcg), intravenously (IV), every 4 weeks i.e. Weeks 4, 8, 12, 16 and 20 but not on Weeks 24 and 28. The initial dose of C.E.R.A.was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA). The ESA therapy was administered from enrollment to the 4 weeks stability verification period (SVP), weekly, either as epoetin (<8000 IU, 8000-16000 IU, or >16000 IU) or darbepoetin alpha (<40 mcg, 40-80 mcg, or >80 mcg). A telephone follow-up visit took place 4 weeks after the end of C.E.R.A. treatment (Week 28). | Drug: methoxy polyethylene glycol-epoetin beta<br>* 120, 200 or 360 micrograms iv every 4 weeks (starting dose)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained Their Mean Hemoglobin Concentration Within +/- 1.0 Gram/Deciliter of Their Reference Hemoglobin Concentration and Between 10.0 and 12.0 Gram/Deciliter During the Efficacy Evaluation Period | The reference hemoglobin (Hb) value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). The time adjusted average Hb concentration of all the values recorded during the efficacy evaluation period (EEP) was calculated for each participant and their reference Hb concentration was subtracted from this value. The percentage of participants maintaining their average Hb concentration during the EEP within +/- 1 gram/deciliter (g/dL) of their reference Hb concentration and between the Hb range 10.0 -12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. Data missing at the end of the EEP was handled using the last value carried forward method, including any data missing due to withdrawal of participants following red blood cells (RBC) transfusion. | EEP (Week 16 to Week 24) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hemoglobin Concentration Between the Stability Verification Period and the Efficacy Evaluation Period | The mean change in the time-adjusted average Hb concentration between the two study periods The Stability Verification Period (SVP) and EEP is presented. The SVP was defined as Week -4 to Week 0. The EEP was defined as Week 16 to Week 24. | SVP (Week -4 to Week 0) and EEP (Week 16 to Week 24) | 
| Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period | The time adjusted average Hb concentration of all the values recorded during the EEP was calculated for each participant. The percentage of participants maintaining their average Hb concentration during the EEP within the Hb concentration range of 10.0-12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. | EEP (Week 16 to Week 24) | 
| Median Time Spent in the Hemoglobin Range 10.0-12.0 Gram/Deciliter During the Efficacy Evaluation Period | The Hb concentration was recorded for all the participants during the EEP. The median time spent (in days) by participants in the target range (10.0-12.0 g/dL) during the EEP is presented. The EEP was defined as Week 16 to Week 24. | EEP (Week 16 to Week 24) | 
| Mean C.E.R.A. Dose Required to Maintain Hemoglobin Level Within the Range 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period | The mean dose of C.E.R.A. required to maintain Hb level between 10.0-12.0 g/dL during the EEP was calculated per participant and then summarized. The EEP was defined as Week 16 to Week 24. However, C.E.R.A. was not administered at the Week 24 visit. Therefore, the time period for calculation of mean C.E.R.A. dose during EEP is from Week 16 to Week 20. | EEP (Week 16 to Week 20) | 
| Percentage of Participants Requiring Any Dose Adjustments in C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period | Dose adjustments were necessary when Hb increased or decreased by a clinically significant amount. The dose of C.E.R.A. was adjusted to maintain the individual participant's Hb within a range of +/- 1.0 g/dL of the reference Hb concentration and between 10.0 and 12.0 g/dL throughout the dose titration period (DTP) and the EEP (Week 1 to Week 24). The reference Hb value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). | DTP (Week 1 to Week 16), EEP (Week 16 to Week 24) | 
| Mean Monthly Dose of C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period | The mean monthly dose of C.E.R.A. administered during the DTP and EEP was calculated per participant and then summarized. | DTP (Week 1 to Week 16), EEP (Week 16 to Week 24) | 
| Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume at Week 16 and Week 24 | Mean change from Baseline in erythrocyte mean corpuscular volume (MCV) was calculated as the value at a specific week during the study minus the BL value. The Baseline was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Hematocrit at Week 16 and Week 24 | The hematocrit, also called packed cell volume or erythrocyte volume fraction, is the volume percentage of red blood cells in the blood. Mean change from Baseline (BL) in hematocrit was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Hemoglobin at Week 16 and Week 24 | Mean change from BL in hemoglobin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Leucocytes and Platelet at Week 16 and Week 24 | Mean change from BL in for each parameter (leucocytes and platelet) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Ferritin at Week 16 and Week 24 | Mean change from BL in ferritin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Iron, Total Iron Binding Capacity, and Creatinine at Week 16 and Week 24 | Mean change from BL in each parameter [iron, total iron binding capacity (TIBC), and creatinine] was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Transferrin and Albumin at Week 16 and Week 24 | Mean change from BL in each parameter (transferrin and albumin) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Transferrin Saturation at Week 16 and Week 24 | Mean change from BL in transferrin saturation (TSAT) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in C-Reactive Protein at Week 16 and Week 24 | Mean change from BL in C-reactive protein was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Phosphate and Potassium at Week 16 and Week 24 | Mean change from BL in each parameter (phosphate and potassium) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change From Baseline in Weight at Week 16 and Week 24 | Mean change from BL in weight was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0. | BL (Week -4 to Week 0), Week 16, and Week 24 | 
| Mean Change in From Baseline in Blood Pressure at Week 16 and Week 24 | Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before blood sampling and C.E.R.A. administration. Blood pressure was assessed both before and after the dialysis session for participants undergoing hemodialysis. Change from BL in blood pressure was calculated as the value at a specific week (W) during the study minus the BL value. The baseline was defined as Week -4 to Week 0. | Baseline (Week -4 to Week 0), Week 16, and Week 24 | 
| Number of Participants Taking Concomitant Medications | The number of participants taking different classes of concomitant medications at any time following enrollment into the study is presented. | Up to Week 28 | 
| Number of Participants With Any Adverse Events and Serious Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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 any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. | Up to Week 28 | 
| Number of Participants With Reports of Anti-erythropoietin Antibodies | The number of participants with Anti-epoetin antibodies is presented. | Up to Week 24 | 
| Number of Participants Who Received Red Blood Cell Transfusions During the Dose Titration Period and Efficacy Evaluation Period | Red blood cell transfusions were permitted during the DTP and EEP (Week 1 to Week 24) in case of medical need. All participants requiring a blood transfusion were withdrawn from the study. The number of participants who were administered RBC transfusions during the DTP and EEP is presented. | Week 1 to Week 24 |