A Study of Subcutaneous Mircera for the Treatment of Anemia in Peritoneal Dialysis Patients.

Study Overview
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Brief Summary
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This 2 arm study will compare the efficacy of monthly Mircera and epoetin alfa in peritoneal dialysis patients who self-inject at home or receive in-centre injections. The safety of subcutaneous (sc) Mircera and injection site reactions and patient satisfaction will also be assessed. Eligible patients will be randomized either to receive monthly sc injections of Mircera (and will be switched from sc epoetin alfa) at a starting dose of 120-360 micrograms, or to remain on standard of care sc epoetin alfa. Dose adjustments will be permitted to reach/maintain a hemoglobin level of 10-12g/dL. The anticipated time on study treatment is 3-12 months, and the target sample size is 380 individuals.

Official Title
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A Two-arm, Randomized, Open-label, Multicenter Study of Safety and Efficacy of Monthly Injections of RO0503821 Versus Epoetin Alfa in Peritoneal Dialysis Patients Who Self Inject or Receive In-center Injections.

Conditions
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Anemia

Intervention / Treatment
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* Drug: Epoetin alfa
* 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 kidney disease stage V; on peritoneal dialysis for 3 months prior to screening; on epoetin alfa sc >=3 months prior to screening. Exclusion Criteria: patients expecting to change dialysis modality over course of study; patients hospitalized during previous 3 months for any clinically significant condition; active malignancy; bleeding episode necessitating transfusion, or overt gastrointestinal bleeding within 3 months prior to screening; transfusion of red blood cells within 3 months prior to screening.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO0503821<br>Eligible participants will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) subcutaneously (SC) every month for eight months (6 months of titration period [TP] and two months of evaluation period [EP] and 15-days following the final study visit (9 months post randomization). The first dose of Mircera (120, 200, or 360 mcg) will be based upon the dose of epoetin alfa received 1 to 2 weeks prior to administration of study drug, while subsequent doses will be adjusted to maintain haemoglobin (Hb) concentrations within target of >=10.0 gram per decilitre (g/dL) and <=12.0 g/dL. Participants who self-administered/visited to clinics for erythropoiesis stimulating agent (ESA) dosing prior to randomization will continue to do so. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* 120-360 micrograms SC monthly, starting dose<br>|
| Active Comparator: Epoetin Alfa<br>Eligible participants will be administered epoetin alfa SC as per the standard of care for eight months (TP and EP), and will be followed-up for 15 days following the final study visit. Participants who self-administered/visited to clinics for ESA dosing prior to randomization will continue to do so. | Drug: Epoetin alfa<br>* As prescribed, SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Hb Concentration to Average Over the Evaluation Period | Mean change in Hb concentration from Baseline (Day [D] 0) to average during the evaluation period (Month 7 to 9) is reported. | From Baseline (D 0) to 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Safety-Related Hb Measures | Safety-related Hb measures included percentage of participants with Hb value > 13 g/dL, 13.5 g/dL, increase in Hb value from baseline by > 2 g/dL or decrease in Hb value from baseline by > 2 g/dL at any time during the study. | Up to Month 9 | 
| Number of Participants With Marked Laboratory Abnormalities | Participants with marked laboratory abnormalities in hematology and clinical chemistry parameters are reported. Hematology laboratory parameters included hematocrit fraction, hemoglobin, platelets, white blood cells (WBCs) and clinical chemistry parameters included aspartate aminotransferase ([AST], alanine aminotransferase ([ALT], creatine phosphokinase (CPK), alkaline phosphatase, albumin, potassium, fasting glucose and phosphate. | Up to Month 9 | 
| Mean Change From Baseline in Iron | Adequate iron status is prerequisite to achieve and maintain target Hb levels. Mean change from Baseline (D 0) in iron to D1 of Months 2, 3, 4, 5, 6, 7, 8 is reported. | From Baseline (D 0) to Month (M) 2, M3, M4, M5, M6, M7, M8 | 
| Mean Change From Baseline in Ferritin | Adequate iron status is prerequisite to achieve and maintain target Hb levels. Mean change from Baseline (D 0) in ferritin to D1 of M2, 3, 4, 5, 6, 7, and 8 is reported. | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 
| Mean Change From Baseline in Transferrin Saturation | Adequate iron status is prerequisite to achieve and maintain target Hb levels. Mean change from Baseline (D 0) in transferrin to D1 of M2, 3, 4, 5, 6, 7, and 8 is reported. | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 
| Mean Change From Baseline in Serum Transferrin | Adequate iron status is prerequisite to achieve and maintain target Hb levels. Mean change from Baseline (D 0) in serum transferrin to D1 of M2, 3, 4, 5, 6, 7, and 8 is reported. | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 
| Mean Change From Baseline in Total Iron-binding Capacity | Adequate iron status is prerequisite to achieve and maintain target Hb levels. Mean change from Baseline (D 0) in total Iron-binding Capacity to D1 of M2, 3, 4, 5, 6, 7, and 8 is reported. | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 
| Mean Change From Baseline in Temperature |  | From Baseline (D 0) to D1 and D15 of M7, M8 | 
| Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure |  | From Baseline (D 0) to D1 and D15 of M7, M8 | 
| Mean Change From Baseline in Pulse Rate |  | From Baseline (D 0) to D1 and D15 of M7, M8 | 
| Mean Change From Baseline in Weight |  | From Baseline (D 0) to D1 and D15 of M7, M8 | 
| Number of Participants With Anti-erythropoietin Antibody in Human Serum | Erythropoietin is human protein which helps to make more RBCs and is used for the treatment of anemia of chronic kidney disease. However, during treatment with erythropoietin, anti-erythropoietin antibody (Anti-EPO) may develop in human serum. These antibodies have been shown to cross-react with all ESAs and leads to failure to respond to treatment. Number of participants with anti-EPO antibody that are quantifiable and those that were below the limit of quantification (BLQ) at Baseline (Day 0) and Visit 17 (Month 9 [M 9]) or final visit/early termination in human serum samples are reported. | Up to Month 9 | 
| Number of Participants With Anti-RO0503821 Antibody in Human Serum | RO0503821 is a chemically modified erythropoietin which helps to make more RBCs and is used for the treatment of anemia of chronic kidney disease. However, during treatment with RO0503821, anti-RO0503821 antibody may develop in human serum. These antibodies have been shown to cross-react with all ESAs and leads to failure to respond. Number of participants with anti- RO0503821 antibody that are quantifiable and those that were BLQ at Baseline (Day 0) and Visit 17 (M 9) or final visit/early termination in human serum samples are reported. | Up to Month 9 | 
| Number of Participants With Any AEs, Any Serious Adverse Events and Death | An AE is untoward medical occurrence in a participant who received the study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is with any of the following outcomes: Death, initial or prolonged inpatient hospitalisation, life-threatening experience, persistent or significant disability/incapacity; congenital anomaly. | Up to 9 months |