Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Mircera is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia associated with chronic kidney disease (CKD) in: • adult patients on dialysis and adult patients not on dialysis ( 1.1 ). • pediatric patients 3 months to 17 years of age on dialysis or not on dialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA ( 1.1 ). FDA label
Also known as Methoxy polyethylene glycol-epoetin beta, RO0503821, CERA, Methoxy polyethylene glycol-epoetin beta (C.E.R.A.)
Mircera · 35 trials · 6 indications
The percentage of participants who maintained their mean Hb concentration within +/- 1 g/dL of their reference Hb and between 10.5 and 12.5 g/dL during the Efficacy Evaluation Period (EEP) is reported. The EEP was from Week 17 to Week 24. The reference Hb was calculated from the mean of Hb concentrations based upon the Hb assessments at Weeks -4, -3, -2, -1, and 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 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.
The reference Hb was defined as the average Hb concentration calculated on the basis of all Hb assessments taken at Weeks -4, -2, and 0 (before the first dose administration).
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to -1). During the EEP (Weeks 18 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the target range of 10.0 to 12.0 g/dL and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.
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.
Percentage of participants maintaining the mean hemoglobin concentration within +/- 1.0 g/dL of their reference hemoglobin value and within the target range of 10.0 to 12.0 g/dL during the efficacy evaluation period (EEP) was assessed. The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the stability verification period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 to Week 24) was estimated as a time adjusted average.
The reference hemoglobin (Hb) value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). The time adjusted average Hb concentration of all the values recorded during the efficacy evaluation period (EEP) was calculated for each participant and their reference Hb concentration was subtracted from this value. The percentage of participants maintaining their average Hb concentration during the EEP within +/- 1 gram/deciliter (g/dL) of their reference Hb concentration and between the Hb range 10.0 -12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. Data missing at the end of the EEP was handled using the last value carried forward method, including any data missing due to withdrawal of participants following red blood cells (RBC) transfusion.
The mean change in Hb concentration between Baseline and Efficacy Evaluation Period (EEP) was calculated by subtracting the baseline Hb concentration from the EEP Hb concentration. Each participant included in this analysis had at least 3 recorded Hb values during EEP, and these Hb values were combined using a time-adjusted average. The EEP was from Week 29 to Week 36.
The target hemoglobin (Hb) range was defined as Hb concentration (gram/deciliter \[g/dL\]) between 10.5 and 12.5 g/dL during the efficacy evaluation period (EEP). EEP was from Week 29 to Week 36.
All mean Hb values recorded during the evaluation period were calculated and subtracted from the mean baseline Hb value for each participant. The percentage of participants maintaining their mean Hemoglobin (Hb) concentration within +/- 1 gram/deciliter (g/dL) of their reference Hb and between 10.5 -12.5 g/dL is presented during the EEP. The EEP is defined as Week 16 to Week 24
The reference Hb value was taken as the time adjusted average of all Hb assessments during the Stability Verification Period (SVP) (Week -4 to Week 0). EEP was from Week 16 to Week 24.
Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-12 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned.
Participants with both hemoglobin values of the evaluation phase (Months 8 and 9, i.e., Study Days 200-260, values were at least 21 days apart) in the range of 11-13 g/dL were classified as responder. Participants who received transfusion of erythrocytes between Study Day 139 and 260, or with at least one value missing or outside the range were classified as non-responder for the hemoglobin-range concerned.
The change from the baseline hemoglobin value to the mean hemoglobin value of the evaluation phase was only calculated if both the baseline value and the mean of the evaluation phase (mean of Months 8 and 9) were available. In case of only one available hemoglobin value within the evaluation phase, that single value replaced the mean.
Participants who maintained average Hb concentration within +/-1 g/dL of their reference Hb and between 10 to 12 g/dL during EEP are reported. The reference Hb value was defined on the basis of all assessments at Weeks -4, -3, -2, -1 and 0.
Hb response was an observed increase in Hb greater than or equal to (\>=) 1.0 gram per deciliter (g/dL) from baseline and an Hb concentration \>= 10.0 g/dL before the end of the study without red blood cells (RBC) transfusion before response.
A time adjusted average baseline Hb concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the 2 month evaluation period (Week 21 to 28). The change in Hb concentration between the baseline and evaluation period was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration.
Key outcomes will be assessed during the first 12 weeks following the 16 weeks dose titration period, i.e. during the Efficacy Evaluation Period (EEP). Assessments performed every four weeks, beginning at week 16 up to week 28. The reference haemoglobin is defined as the mean of the two assessments recorded during the SVP (weeks -4 and -2). For the purposes of efficacy assessment the target haemoglobin concentration range will be defined as ± 1 g/dL of the reference haemoglobin concentration AND within the range 10 - 12 g/dL.
Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL compared with baseline and Hb\>/=11 g/dL without red blood cell transfusion during 24-week correction phase. The average baseline value was estimated by the mean of all values recorded between the day of first study dose and the previous 20 days. The percentage of participants who achieved Hb response is presented
Percentage of participants maintaining their mean hemoglobin concentration in g/dL within plus or minus (+/-) 1 g/dL of their reference hemoglobin value, and between the target range of 10.0 and 12.0 g/dL during the efficacy evaluation period (EEP). The reference hemoglobin value was defined on the basis of the 5 assessments recorded during the Stability Verification Period (SVP) at Weeks -4, -3, -2, -1 and 0. The mean hemoglobin concentration for each individual participant during the EEP (Week 17 up to Week 24) was estimated as a time adjusted average.
The haemoglobin (Hb) levels were recorded for each participant at enrollment and at different time points during the study up to Week 48. The reference Hb value was defined on the basis of individual participant's all assessments at Weeks -4, -3, -2, -1 and 0. The Hb value on the first day of first dose (Week 0) was included in the calculation, as this assessment was performed before the first dose was given. The percentage of participants maintaining their mean Hb concentration within +/-1.0 gram/deciliter (g/dL) of their reference Hb and between 10.5 and 12.5 g/dL are reported for efficacy evaluation period (EEP). Efficacy evaluation period was from Week 16 to Week 24 after completion of 16-week dose titration period (DTP).
Reference Hb was determined individually per participant as the average of all Hb values during a pre-treatment stability assessment (Weeks -4 to 0). During the EEP (Weeks 18 to 24), participants provided a total of four pre-dose blood samples for Hb monitoring while on treatment with Mircera/CERA. Sampling was also performed prior to each dialysis session. The average Hb during the EEP was calculated per participant and assessed against the reference value. The percentage of participants who had average Hb during the EEP in the country-specific target range (11.0 to 13.0 g/dL in Switzerland and 10.0 to 12.0 g/dL in Austria) and within ±1 g/dL of their individual reference Hb was determined as the primary endpoint. The 95 percent (%) confidence interval (CI) was calculated using the Pearson-Clopper method for exact confidence bounds.
A time adjusted average baseline hemoglobin (Hb) concentration was calculated using the trapezoid rule from all available Hb measurements taken during the baseline period. The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the two month evaluation period. The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb from the evaluation period Hb. All blood samples for Hb measurements were taken prior to study drug administration.
Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.
Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.
Randomized participants with an average hemoglobin (Hb) decrease from Baseline (Week -4 to Week -1) not exceeding 1.0 gram per deciliter (g/dL) and an absolute average Hb \>= 10.5 g/dL during the evaluation period (Weeks 50-53) were defined as responders. Non-responders included participants without any Hb data during the second treatment period and those who did not meet the response criteria and thus were not included in the analysis.
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.
A time adjusted mean change in hemoglobin (Hb) concentration was calculated using an area under the curve approach, for both periods separately. Change in Hb concentration between the baseline (Week -4 to Week -1) and evaluation periods was calculated by subtracting the calculated average baseline Hb value from the average evaluation period Hb value. All blood samples for Hb measurements were taken prior to study drug administration. The analysis used the last observation carried forward (LOCF) for missing Hb values for correction of the impact of early drop outs. The baseline period was defined as Week -4 to Week -1. The evaluation period was defined as Week 29 to Week 36.
The Hb change from baseline was calculated on a per-participant basis using an individual's average for both the baseline and evaluation periods and taking the difference. The baseline period was defined as the time between the day of first study dose and the previous 35 days. The evaluation period was defined as the period between Week 17 and Week 21, inclusive.
The yearly reduction in eGFR was calculated using the MDRD-4 formula. This formula is based on age, sex, and serum creatinine and eGFR values are calculated as follows: GFR in milliliter per minute (mL/min) per 1.73 meter square (m\^2) = 175 x Serum Cr\^-1.154 x age\^-0.203 x 0.742 (if female). The yearly reduction rate (mL/min/1.73m\^2 / Year) is defined as -365.25 multiplied by Beta, where Beta is the slope parameter derived for each participants separately by simple linear regression of the change from baseline in participant's eGFR measurements (from Baseline to Visit 24) on the actual day of measurement.
A time adjusted average baseline Hb concentration for each individual was calculated using an area under the curve (AUC) approach from all available Hb measurements taken during the baseline period (Day -20 to Day 1). The average evaluation period Hb concentration for each individual was calculated using the same method, from all their available measurements taken during the evaluation period (Week 17 to Week 21). The change in Hb concentration between the baseline and evaluation periods was calculated by subtracting the baseline Hb concentration from the evaluation period Hb concentration.
Median change from Baseline in hemoglobin (Hb) levels to end of initial treatment (EOIT) under constant dosing regimen was reported. For ease of interpretation, all individual slope values were multiplied by 42 to give an estimate of change in Hb values over six weeks. Baseline (Day -28 to Day 1) Hb values was calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1). For all participants, an EOIT value was calculated as the last observed Hb value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 value.
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.
| Arm | Type | Description |
|---|---|---|
| C.E.R.A. | EXPERIMENTAL | Eligible participants will be administered continuous erythropoietin receptor activator (C.E.R.A.\[Mircera\]) intravenously (IV) every 4 weeks for 44 weeks. The starting dose of 120, 200, or 360 micrograms (mcg) will be based on the dose of epoetin alfa or beta administered in the week preceding the switch to C.E.R.A. Subsequent doses will be adjusted to maintain the individual participant's hemoglobin (Hb) within a range of +/- 1.0 grams per deciliter (g/dL) of the reference hemoglobin (Hb) concentration and between 10.50 and 12.50 g/dL. |
| Mircera in Renal Anemia | EXPERIMENTAL | 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. |
| Methoxy Polyethylene Glycol-Epoetin Beta | EXPERIMENTAL | Participants will receive methoxy polyethylene glycol-epoetin beta once monthly by subcutaneous (SC) injection for 28 weeks. |
| Continuous erythropoietin receptor activator (C.E.R.A.) | EXPERIMENTAL | 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. |
| Epoetin Beta or Darbepoetin Alfa | ACTIVE_COMPARATOR | Participants who are receiving SC or IV epoetin beta or darbepoetin alfa will continue to receive the same treatment (epoetin beta or darbepoetin alfa at the same dose, same administration intervals, and the same route of administration). When necessary, dose adjustments will be performed according to Summary of Product Characteristics (SmPC). Total duration of treatment will be up to 48 weeks. |
| C.E.R.A. 120, 200, or 360 mcg | EXPERIMENTAL | Eligible participants were administered Continuous Erythropoietin Receptor Activator (C.E.R.A.) at a dose of 120, 200, or 360 microgram (mcg), intravenously (IV), every 4 weeks i.e. Weeks 4, 8, 12, 16 and 20 but not on Weeks 24 and 28. The initial dose of C.E.R.A.was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA). The ESA therapy was administered from enrollment to the 4 weeks stability verification period (SVP), weekly, either as epoetin (\<8000 IU, 8000-16000 IU, or \>16000 IU) or darbepoetin alpha (\<40 mcg, 40-80 mcg, or \>80 mcg). A telephone follow-up visit took place 4 weeks after the end of C.E.R.A. treatment (Week 28). |
| C.E.R.A | EXPERIMENTAL | Participants received methoxy polyethylene glycol-epoetin beta (Continuous Erythropoietin Receptor Activator \[C.E.R.A\]) subcutaneously every four weeks for 44 weeks. The participants received initial dose of 1.2 microgram per kilogram (mcg/kg) of C.E.R.A. Once the Hemoglobin (Hb) concentration was attained within the target range of 11.0 and 13.0 gram per deciliter (g/dL), the dose was adjusted to maintain the Hb concentration within the target range. |
| 1 | EXPERIMENTAL | - |
| 2 | ACTIVE_COMPARATOR | - |
| RO0503821 (C.E.R.A.), 1x/4weeks | EXPERIMENTAL | Eligible participants started RO0503821 (Continuous Erythropoietin Receptor Activator \[C.E.R.A\]) intravenously, at a dose of 120, 200 or 360 microgram (µg) every four weeks. The dose of C.E.R.A was based on the epoetin alfa or beta dose of\<8000, 8000-16000, or \>16000 international units (IU)/week, administered during the stability verification period (SVP) of 4 weeks. The SVP period was followed by dose titration period (DTP) of 16 weeks, efficacy evaluation period (EEP) of 8 weeks and long term safety period (LTSP) of 28 weeks |
| Epoetin Alfa | ACTIVE_COMPARATOR | Participants received IV injection of 6000 International Units (IU) of epoetin alfa every 3 weeks (q3wk) during the Stability Verification Period (SVP; Week -4 to -1), and 7443 IU of epoetin alfa q3wk during Dose Titration Period (DTP; Week 0 to 15), 7363 IU of epoetin alfa q3wk during Efficacy Evaluation Period (EEP; Week 16 to 23) up to 23 weeks. |
| Mircera | EXPERIMENTAL | Participants will receive Mircera (Methoxy polyethylene glycol-epoetin beta), administered subcutaneously (SC) at a starting dose of 1.2 mcg/kg once every 4 weeks for 28 weeks. |
| Darbepoetin Alfa | ACTIVE_COMPARATOR | Participants will receive darbepoetin alfa, administered SC once weekly or once every 2 weeks according to local labeling specifications for 28 weeks. |
| CERA Treatment Once Monthly | EXPERIMENTAL | - |
| Darbepoetin Alfa Once Biweekly | ACTIVE_COMPARATOR | - |
| Correction Phase: CERA | EXPERIMENTAL | - |
| Correction Phase: Epoetin Beta | ACTIVE_COMPARATOR | - |
| Comparator ESA | ACTIVE_COMPARATOR | 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. |
| RO0503821 (1x/2 Weeks) | EXPERIMENTAL | Eligible participants will be administered with RO0503821 (\[methoxy polyethylene glycol-epoetin beta\] {Mircera}) intravenously (IV), every 2 weeks during Weeks 1 through 52. The starting dose of RO0503821 (60, 100, or 180 micro gram \[µg\]) was based on the dose of darbepoetin alfa at the time of randomization (\< 40, 40 to 80, or \> 80 µg per week, respectively). |
| Darbepoetin (1x/1-2 Weeks) | ACTIVE_COMPARATOR | Eligible participants will be administered with darbepoetin alfa IV, every week or every 2 weeks during Weeks 1 through 52. |
| Placebo | PLACEBO_COMPARATOR | - |
| MIRCERA Group 1: Intermediate-Conversion-Factor Group | EXPERIMENTAL | Participants will receive methoxy polyethylene glycol-epoetin beta (MIRCERA) IV injection at a starting dose based on an intermediate conversion factor from their previous Erythropoiesis-stimulating Agent (ESA) dose (4 \* previous weekly epoetin dose \[international units {IU}\]/250 or 4 \* previous weekly darbepoetin alfa dose \[micrograms {mcg}\]/1.1) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with hemoglobin (Hb) level within ± 1 grams per deciliter (g/dL) of their baseline Hb level and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks. |
| MIRCERA Group 2: High-Conversion-Factor Group | EXPERIMENTAL | Participants will receive MIRCERA IV injection based on a high conversion factor from their previous ESA dose (4 \* previous weekly epoetin dose \[IU\]/125 or 4 \* previous weekly darbepoetin alfa dose \[mcg\]/0.55) once every 4 weeks for 20 weeks. Participants who will complete the 20 weeks of treatment with Hb within ± 1 g/dL of their baseline Hb and within the target range of 10-12 g/dL will enter an optional 52-weeks safety extension period. During this period, the participants will continue to receive MIRCERA IV injection once every 4 weeks. |
| Mircera 6.3 micrograms/kg | EXPERIMENTAL | - |
| Mircera 9 micrograms/kg | EXPERIMENTAL | - |
| Mircera 12 micrograms/kg | EXPERIMENTAL | - |
| Cohort 1 (RO0503821 [0.25/150 1x/week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) intravenously (IV) using a dose conversion factor of 0.25/150 microgram (mcg)/kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 2 (RO0503821 [0.25/150 1x/2week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to 62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 3 (RO0503821 [0.4/150 1x/week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 4 (RO0503821 [0.4/150 1x/2week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 5 (RO0503821 [0.6/150 1x/week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 6 (RO0503821 [0.6/150 1x/2week]) | EXPERIMENTAL | Eligible participant will be administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) | EXPERIMENTAL | 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. |
| Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) | EXPERIMENTAL | 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. |
| Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) | EXPERIMENTAL | 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. |
| Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) | EXPERIMENTAL | 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. |
| Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) | EXPERIMENTAL | 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. |
| Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) | EXPERIMENTAL | 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. |
| Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) | EXPERIMENTAL | 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. |
| Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) | EXPERIMENTAL | 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. |
| Cohort 9 (RO0503821,1.8 mcg/kg 1x/3 Week) | EXPERIMENTAL | 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. |
| Cohort A (0.4/150, 1x/ Week) | EXPERIMENTAL | Eligible participant will be administered RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) SC using a dose conversion factor of 0.4/150 microgram (mcg)/ kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort B (0.4/150, 1x/ 3 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort C (0.4/150, 1x/ 4 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort D (0.8/150, 1x/ Week) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort E (0.8/150, 1x/ 3 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort F (0.8/150, 1x/ 4 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort G (1.2/150, 1x/ Week) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort H (1.2/150, 1x/ 3 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three weeks up to 19 weeks. After 19 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Cohort I (1.2/150, 1x/ 4 Weeks) | EXPERIMENTAL | Eligible participant will be administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants will be followed-up for two optional treatment extension periods (54 weeks each). |
| Name | Type | Description |
|---|---|---|
| methoxy polyethylene glycol-epoetin beta [Mircera] | DRUG | Subcutaneous injection every 4 weeks (starting dose of 120, 200 or 360 micrograms, based on previous ESA therapy) |
| Methoxy polyethylene glycol-epoetin beta | DRUG | 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. |
| Epoetin Beta | DRUG | Participants who are receiving SC or IV epoetin beta will continue to receive the treatment at the same dose, same administration intervals, and the same route of administration. When necessary, dose adjustments will be performed according to SmPC. Total duration of treatment will be up to 48 weeks. |
| Darbepoetin Alfa | DRUG | Participants who are receiving SC or IV darbepoetin alfa will continue to receive the treatment at the same dose, same administration intervals, and the same route of administration. When necessary, dose adjustments will be performed according to SmPC. Total duration of treatment will be up to 48 weeks. |
| Methoxy polyethylene glycol-epoetin beta (C.E.R.A.) | DRUG | Intravenous methoxy polyethylene glycol-epoetin beta (C.E.R.A.) at starting dose of 120, 200, or 360 micrograms every 4 weeks for 24 weeks. |
| methoxy polyethylene glycol-epoetin beta [C.E.R.A.] | DRUG | Recommended starting dose 1.2 micrograms/kg sc monthly |
| Epoetin alfa | DRUG | As prescribed |
| methoxy polyethylene glycol-epoetin beta [RO0503821, Mircera] | DRUG | 0.6 micrograms/kg every 2 weeks |
| Epoetin | DRUG | As prescribed, iv, 3 times weekly |
| Mircera | DRUG | Starting dose of 120, 200 and 360 micrograms administered by subcutaneous injection once a month. |
| Placebo | DRUG | Placebo matching to Methoxy polyethylene glycol-epoetin beta subcutaneous injection once monthly up to 24 months. |
Inclusion Criteria: * adult patients \>=18 years of age; * chronic renal anemia; * regular long-term hemodialysis or peritoneal dialysis, with same mode of dialysis for \>=3 months; * continuous iv maintenance epoetin alfa therapy with same dosing interval during previous 2 months. Exclusion Crite...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Bristol-Myers Squibb Company | BMY | 2 | PHASE3 | Luspatercept |
| Takeda Pharmaceutical Co. Ltd. Sponsored ADR | TAK | 2 | PHASE3 | Elritercept |
| Disc Medicine, Inc. | IRON | 2 | PHASE2 | DISC-0974 |
| Akebia Therapeutics, Inc. | AKBA | 2 | PHASE3 | Vadadustat |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | APG-5918 |
| Bayer | BAYRY | 1 | - | Molidustat |
Mircera is used for the treatment of anemia, including anemia associated with chronic kidney disease. It is being studied in patients with chronic kidney disease who are on dialysis or not yet on dialysis. The drug is administered subcutaneously.
Mircera is developed by Roche Holding AG, a company traded under the ticker RHHBY. Roche is conducting clinical trials to evaluate the drug's use in treating anemia in patients with chronic kidney disease.
Mircera is in Phase 3 clinical development for the treatment of anemia. It has completed Phase 3 and Phase 2 trials, with two completed studies involving a total of 268 participants. The drug remains investigational and is not yet approved.
Mircera has been studied in two completed clinical trials. NCT00442702 was a Phase 3 study in adults with chronic kidney disease not on dialysis, enrolling 228 participants. NCT03552393 was a Phase 2 study in pediatric patients with chronic kidney disease, enrolling 40 participants.
Mircera is not FDA approved. It is an investigational drug currently in clinical development for anemia. The completed trials have evaluated its use in chronic kidney disease patients, but the drug has not received regulatory approval.