A Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis.

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of different subcutaneous starting doses and dosing frequencies of Mircera in anemic patients with chronic kidney disease not yet on dialysis. The anticipated time on study treatment is 3-12 months and the target sample size is <100 individuals.

Official Title
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An Open-label, Randomized, Multi-centre, Multiple Dose Trial to Investigate the Efficacy and Safety of Subcutaneous Injections of RO0503821 at Different Dosing Intervals in Patients With Chronic Renal Anemia Who Are Not on Renal Replacement Therapy

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; not receiving renal replacement therapy. Exclusion Criteria: women who are pregnant, breastfeeding or using unreliable birth control methods; administration of any investigational drug within 30 days preceding the screening visit and during the run-in period.

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: Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week)<br>Eligible participants will be receiving RO0503821 (methoxy polyethylene glycol-epoetin beta [Mircera]) at a dose of 0.15 microgram per kilogram (mcg/kg) subcutaneously (SC) once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week)<br>Eligible participants will be receiving RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week)<br>Eligible participants will be receiving RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|
| Experimental: Cohort 9 (RO0503821,1.8 mcg/kg 1x/3 Week)<br>Eligible participants will be receiving RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants will be followed-up for one week post the treatment period. During extension Years 1 and 2, the participants will remain at the same frequency of administration as that of core treatment period. | Drug: methoxy polyethylene glycol-epoetin beta [Mircera]<br>* Differing doses and frequencies of sc administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Change in Hemoglobin Over Time Between Baseline and End of Initial Treatment Based on Individual Regression Slopes | The primary efficacy variable was blood Hb level and its changes from Baseline (defined as the mean Hb of Screening assessment (SA) (Week -3), Weeks -2 and -1 of the Run-in period) over time during the core treatment period. For each participant, the primary efficacy parameter was the change in hemoglobin level over time based on regression slopes. All values until end-of-initial treatment (EOIT), defined as the last observed value before a dose change or blood transfusion, were included in the calculation of this endpoint. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19. | From Baseline (Day -28 to Day 1) to EOIT (Week 19) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematocrit Levels at End of Initial Treatment Under Constant Dosing Regimen | Hematocrit (Hct) levels at end of initial treatment under constant dosing regimen were reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19. | From Baseline (Day -28 to Day 1) to EOIT (Week 19) | 
| Reticulocyte Count at End of Initial Treatment Under Constant Dosing Regimen | Reticulocyte levels at EOIT under constant dosing regimen was analysed and reported. Baseline (Day -28 to Day 1) reticulocyte values were calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed reticulocyte count before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19. | From Baseline (Day -28 to Day 1) to EOIT (Week 19) | 
| Number of Participants With Any Serious Adverse Events and Any Adverse Events | An Adverse Events (AEs) is defined as 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. Serious Adverse Events (SAEs) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only. | Up to Week 125 | 
| Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time | Marked abnormality was defined as above and/or below a value (according to the Roche specified limits) which was considered to be potentially clinically relevant. The Roche reference range are: white blood cells (WBC) (3.0-18.0 10^9 cells/L), platelets (100-550 10^9 cells/L), alanine aminotransferase (ALT) [0-110 units per litre (U/L)], alkaline phosphatase (ALP) (0-220 U/L), aspartate aminotransferase (AST) (0-80 U/L), albumin >= 30 g/L, phosphate [0.75 - 1.60 millimoles per liter (mmol/L)], potassium (2.9 - 5.8 mmol/L), total bilirubin (0-17 µmol/L), lymphocytes (1- 4.80 10^9 cells/L), eosinophils (0 - 0.45 10^9 cells/L), monocytes (0 - 0.8 10^9 cells/L), and neutrophils (1.80 - 7.70 10^9 cells/L). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time, all results for the two long term safety periods were displayed by dose schedule group only. | Up to Week 125 | 
| Heart Rate Over Time | Heart rate was defined as the measure of heart beats per minute (bpm). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only. | Up to Week 125 | 
| Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) values were calculated as the mean of the SA (Week -3) and Run-in period (Week -2 and Week -1). | From Baseline (Day -28 to Day 1) to Week 125 |