A Study of Monthly Subcutaneous Mircera for the Treatment of Chronic Renal Anemia in Predialysis Patients Not Treated With ESA.

Study Overview
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Brief Summary
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This single arm study will assess the efficacy and safety of subcutaneous methoxy polyethylene glycol-epoetin beta (Mircera) for the correction and maintenance of hemoglobin levels in predialysis patients with renal anemia who are not currently treated with erythropoietin stimulating agents (ESA). Eligible patients will receive monthly subcutaneous injections of Mircera at an initial recommended dose of 1.2 micrograms/kg. 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 Subcutaneous C.E.R.A. for the Treatment of Chronic Renal Anaemia in Pre-dialysis Patients Not Currently Treated With ESA.

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; predialysis stage; no ESA therapy during previous 3 months. Exclusion Criteria: transfusion of red blood cells during previous 2 months; poorly controlled hypertension requiring hospitalization 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: Continuous erythropoietin receptor activator (C.E.R.A.)<br>Eligible participants will be administered C.E.R.A subcutaneously, every 4 weeks for 44 weeks. The initial dose of C.E.R.A. will be 1.2 micrograms/kilogram. Subsequent doses will be adjusted to maintain the individual participant's hemoglobin within the target range of 10.0 and 12.0 grams/deciliter. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* sc every month (starting dose 1.2 micrograms/kg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period | Mean change in Hb concentration was calculated as the difference between the time adjusted average of Hb during the efficacy evaluation period (EEP [Week 29 to Week 36]), and the Hb at Baseline (Week 0). A positive change from baseline indicates improvement. | From Baseline (Week 0) to EEP (Week 29 to Week 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Time to Achievement of Response During the EEP | Participants with Hb concentrations within target range of 10-12 g/dl were considered to be responders. Mean time to achievement of response during the EEP (Week 29 to Week 36) is presented. | From Week 29 to Week 36 | 
| The Percentage of Participants Whose Hb Concentrations Remained Within the Target Range of 10.0- 12.0 g/dLThroughout the EEP | The percentage of participants whose Hb Concentrations remained within the target range of 10.0- 12.0 g/dL throughout the EEP (Week 29 to Week 36) is presented. | From Week 29 to Week 36 | 
| Mean Time Spent by Participants in the Target Range of 10.0- 12.0 g/dL During the EEP | Mean time spent by participants in the target range of 10.0- 12.0 g/dL during the EEP (Week 29 to Week 36) is presented. | From Week 29 to Week 36 | 
| Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Percentage of participants requiring dose adjustments during dose titration period (DTP [Week 0 to Week 28]) and EEP (Week 29 to Week 36) is presented. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either ≥ 13 g/dL or < 9 g/dL; if the difference of 2 consecutive Hb concentrations was ≥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 to 12 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 10.5 to 11.5 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted. | Weeks 0 to Week 36 | 
| Number of Participants Who Received Red Blood Cell Transfusions During the Study Period | Red blood cell transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP (Week 0 to Week 28), EEP (Week 29 to Week 36), and during the long term safety period (LSTP [Week 37 to Week 52]) are presented. | Up to Week 52 | 
| Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant 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 52 | 
| Mean Change From Baseline in Hb Concentration Over Time | Mean change from Baseline in Hb concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Hematocrit Level Over Time | Mean change from Baseline in hematocrit level was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Mean change from Baseline in erythrocyte mean corpuscular volume was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, and 48 | 
| Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Mean change from Baseline in white blood cells (WBCs) and platelets concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Albumin Concentration Over Time | Mean change from Baseline in albumin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Mean change from Baseline in C-Reactive Protein concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Mean change from Baseline in phosphate and potassium concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Mean change from Baseline in total iron binding capacity (TIBC) and iron concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Creatinine Concentration Over Time | Mean change from Baseline in creatinine concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 32, 40 | 
| Mean Change From Baseline in Ferritin Concentration Over Time | Mean change from Baseline in ferritin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | 
| Mean Change From Baseline in Transferrin Saturation Over Time | Mean change from Baseline in transferrin saturation (TSAT) was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 |