A Study of Intravenous or Subcutaneous Methoxy Polyethylene Glycol-Epoetin Beta (RO0503821, Mircera) in Chronic Kidney Disease Patients With Renal Anemia

Study Overview
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Brief Summary
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This study assessed the long-term efficacy, safety, and tolerability of intravenous (iv) or subcutaneous (sc) methoxy polyethylene glycol-epoetin beta in chronic kidney disease patients with renal anemia. Eligible patients were those who were receiving stable maintenance therapy with methoxy polyethylene glycol-epoetin beta or erythropoiesis stimulating agents (ESAs) in Phase II or III clinical studies. They continued to receive methoxy polyethylene glycol-epoetin beta or comparator ESAs at the same weekly dose and by the same route of administration (sc or iv) as in the qualifying studies.

Official Title
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An Open-label, Multi-center Study to Document the Efficacy, Safety, and Tolerability of Long-term Administration of RO0503821 in Patients With Chronic Renal Anemia

Conditions
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Anemia

Intervention / Treatment
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* Drug: Methoxy Polyethylene Glycol-Epoetin Beta
* Drug: Epoetin alfa
* Drug: Epoetin beta
* Drug: Darbepoetin alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Adult patients (≥ 18 years old) with chronic renal anemia Maintenance erythropoietic therapy with methoxy polyethylene glycol-epoetin beta or a protocol-specified reference medication (epoetin alfa formulated with human albumin, epoetin beta or darbepoetin alfa) in one of the following studies: BA16528[NCT00048048], BA16285[NCT00048035], BA16286[NCT00364832], BA16736[NCT00077597], BA16738[NCT00081471], BA16739[NCT00077610], BA16740[NCT00077623], BA17283[NCT00077766] and BA17284[NCT00081484] Hemoglobin (Hb) concentration between 10.5 and 13.0 g/dL Adequate iron status defined as serum ferritin ≥ 100 ng/mL or Transferrin Saturation (TSAT)≥ 20% or percentage of hypochromic red blood cells (RBCs) < 10% Exclusion Criteria: Poorly controlled hypertension History of epileptic seizure Pure red cell aplasia Chronic congestive heart failure [New York Heart Association (NYHA) IV] High likelihood of early withdrawal or interruption of the study Active malignant disease (except non-melanoma skin cancer) Life expectancy less than 12 months Pregnancy or breast-feeding

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methoxy Polyethylene Glycol-Epoetin Beta<br>Patients received the same weekly dose of methoxy polyethylene glycol-epoetin beta via the same route of administration (iv or sc) as they received in the Phase II or Phase III study that qualified the patient for participation in this study. Methoxy polyethylene glycol-epoetin beta was administered every 2 or every 4 weeks in the initial 104-week treatment period. Patients on a 4-week dosing interval were switched to once-monthly administration in the 24-month extension phase. The dose of methoxy polyethylene glycol-epoetin beta was adjusted to maintain the patient's hemoglobin (Hb) within a target range of 11 to 13 g/dL. | Drug: Methoxy Polyethylene Glycol-Epoetin Beta<br>* Methoxy polyethylene glycol-epoetin beta was provided as a sterile single-use injectable solution in 2-mL glass vials containing 1 mL solution or in single-use sterile pre-filled syringes (PFSs) containing 0.3 mL or 0.6 mL injectable solution. The injectable solution was available in vials with the following strengths: 50, 100, 200, 400, and 1000 μg/mL. The injectable solution was available in PFSs with the following strengths: 30, 40, 50, 60, 75, 100, 120, 150, 200, and 250 μg/0.3 mL; and 360 and 400 μg/0.6 mL.<br>* Other names: Mircera;|
| Active Comparator: Comparator ESA<br>Patients received the same comparator ESA [epoetin alfa, epoetin beta, or darbepoetin alfa] at the same weekly dose and dosing interval via the same route of administration (iv or sc) as they received in the Phase III study that qualified the patient for participation in this study. The dose of the comparator drug was adjusted to maintain the patient's Hb within a target range of 11 to 13 g/dL. Of the 480 patients in the comparator drug group, 170 received darbepoetin alfa, 134 received epoetin alfa, and 176 received epoetin beta. | Drug: Epoetin alfa<br>* Epoetin alfa was provided with commercial packaging in English with country-specific labels (10,000 IU, 20,000 IU).<br>Drug: Epoetin beta<br>* Epoetin beta was provided with commercial packaging in English with country-specific labels (50,000 IU, 100,000 IU).<br>Drug: Darbepoetin alfa<br>* Darbepoetin alfa was provided with commercial packaging in English with country-specific labels (vials and PFSs in various strengths).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Hemoglobin Concentration to the Last Month of Study Participation | Blood samples were collected at each study visit, that is, every 4 weeks for the first 12 weeks, every 12 weeks until week 105 of the first study period, every 3 months thereafter, and at the end of study or the last visit if the patient discontinued the study prematurely. | Baseline to the end of the study (Up to 49 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Had at Least 1 Adverse Event | See the adverse events section of the results for more information. | From first dose of study drug to date of last contact or 30 days after last drug dose (Up to 49 months) |