A Study of Monthly Subcutaneous (SC) Mircera for Maintenance Treatment of Participants With Chronic Kidney Disease on Peritoneal Dialysis

Study Overview
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Brief Summary
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This single-arm study will assess the efficacy and safety of monthly administration of SC Mircera for the maintenance of hemoglobin levels in participants with chronic kidney disease on peritoneal dialysis. Participants currently receiving maintenance treatment with SC erythropoietin stimulating agents (ESAs) will receive monthly SC injections of Mircera, with the starting dose derived from the last weekly ESA they had been receiving.

Official Title
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A Single Arm, Open-Label, Multicentre Study to Assess the Maintenance of Haemoglobin Levels With Once Monthly Subcutaneous Administration of C.E.R.A (Continuous Erythropoietin Receptor Activator) in Patients With Chronic Kidney Disease on Peritoneal Dialysis

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: Adults greater than or equal to (≥) 18 years of age Chronic kidney disease-related anemia on peritoneal dialysis for ≥3 months Continuous SC maintenance stable ESA therapy for 4 weeks prior to study start Exclusion Criteria: Transfusion of red blood cells during previous 8 weeks Poorly controlled hypertension requiring interruption of ESA treatment in previous 6 months Significant acute or chronic bleeding during previous 8 weeks

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: Mircera in Renal Anemia<br>Participants will receive SC methoxy polyethylene glycol-epoetin beta (Mircera) every 4 weeks for a total of 48 weeks in this single-arm study. The first dose of 120 or 200 micrograms (mcg) will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within the target range. | Drug: Methoxy polyethylene glycol-epoetin beta<br>* Mircera will be administered SC every 4 weeks for a total of 48 weeks. The first dose of 120 or 200 mcg will be determined by the dose of ESA received prior to administration of study treatment, while subsequent doses will be adjusted to maintain hemoglobin within the target range.<br>* Other names: CERA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Maintained Average Hb Value Within Target Range During the EEP | Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) was calculated per participant and assessed against the target range. The percentage of participants who had average Hb during the EEP in the target range (10 to 12 g/dL) was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds. | Weeks 16 to 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Hb Values Within Target Range During the EEP | During the EEP (Weeks 16 to 24), participants provided a total of three pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had at least one, two, or all three Hb values during the EEP in the target range (10 to 12 g/dL) was determined. | Weeks 16 to 24 | 
| Change in Hb Value From Baseline to the EEP | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP (Weeks 16 to 24) was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., Baseline) Hb and the EEP average Hb was calculated and expressed in g/dL. | Baseline and Weeks 16 to 24 | 
| Time Spent in the Target Range for Hb During the EEP and the Overall Treatment Period | Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range (10 to 12 g/dL) was defined as time from first on-target Hb measurement to time of last known on-target Hb measurement, as collected during the EEP (Weeks 16 to 24) and the overall treatment period (Weeks 0 to 48). Time spent in the target range was averaged among all participants and expressed in weeks. | Weeks 16 to 24 and Weeks 0 to 48 | 
| Percentage of Participants With Hb Value Within Plus/Minus (±) 1 g/dL of Reference Hb and Within the Target Range by Study Visit | Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment screening period (Weeks -4 to 0). Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. The percentage of participants who had average Hb during the EEP (Weeks 16 to 24) and follow-up (Weeks 28 to 48) in the target range (10 to 12 g/dL) and within ±1 g/dL of their individual reference Hb was determined by study visit. | Baseline and Weeks 16, 20, 24, 28, 32, 36, 40, 44, 48 | 
| Percentage of Participants With Cycles or Excursions | Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Cycles were defined as a change in Hb greater than (>) 1.5 g/dL lasting longer than 8 weeks. Excursions were defined as half of one full cycle, or an increase (up excursions) or decrease (down excursions) >1.5 g/dL lasting longer than 4 weeks according to Hb measurements collected during the study. The percentage of participants with at least one cycle or excursion during Weeks 4 to 44 was calculated. | Weeks 4 to 44 | 
| Percentage of Participants With Up Excursions | Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase (up excursions) or decrease (down excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one up excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44. | Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44 | 
| Percentage of Participants With Down Excursions | Participants provided pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA during the DAP, EEP, and follow-up. Excursions were defined as half of one full cycle, or an increase (up excursions) or decrease (down excursions) in Hb >1.5 g/dL lasting longer than 4 weeks. The percentage of participants with at least one down excursion was calculated for Weeks 4 to 16, Weeks 16 to 24, and Weeks 24 to 44. | Weeks 4 to 16, Weeks 16 to 24, Weeks 24 to 44 | 
| Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA | Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percentage of participants who required any dose adjustment (including decreased dose, increased dose, and dose not performed) was calculated for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48. | Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48 | 
| Number of Dose Adjustments of Mircera/CERA | Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The number of dose adjustments performed for each participant was averaged among all participants for Weeks 4 to 20, Weeks 24 to 48, and Weeks 4 to 48. | Weeks 4 to 20, Weeks 24 to 48, Weeks 4 to 48 | 
| Absolute Change in Dose of Mircera/CERA by Study Week | Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The absolute difference in dose from the previous week was calculated at each visit and averaged among all participants. | Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | 
| Percent Change in Dose of Mircera/CERA by Study Week | Study drug administration occurred monthly during treatment (Weeks 0 to 48), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during the initial 4-week screening period. Subsequent doses could be adjusted on the basis of Hb levels or other modification criteria. The percent difference in dose from the previous week was calculated at each visit as [(current dose minus previous week dose) divided by previous week dose] multiplied by 100, and averaged among all participants. | Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 | 
| Percentage of Participants Requiring Blood Transfusions | The percentage of participants who received at least one red blood cell transfusion during the overall treatment period (Weeks 0 to 48) was calculated. | Weeks 0 to 48 |