Anemia
Conditions
Brief summary
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.
Interventions
DRUGEpoetin alfa
As prescribed, SC
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
120-360 micrograms SC monthly, starting dose
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Hb Concentration to Average Over the Evaluation Period | From Baseline (D 0) to 9 months | Mean change in Hb concentration from Baseline (Day \[D\] 0) to average during the evaluation period (Month 7 to 9) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Marked Laboratory Abnormalities | Up to Month 9 | 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. |
| Mean Change From Baseline in Iron | From Baseline (D 0) to Month (M) 2, M3, M4, M5, M6, M7, M8 | 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. |
| Mean Change From Baseline in Ferritin | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 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. |
| Mean Change From Baseline in Transferrin Saturation | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 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. |
| Mean Change From Baseline in Serum Transferrin | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 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. |
| Mean Change From Baseline in Total Iron-binding Capacity | From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8 | 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. |
| Percentage of Participants With Safety-Related Hb Measures | Up to Month 9 | 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. |
| 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 | Up to Month 9 | 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. |
| Number of Participants With Anti-RO0503821 Antibody in Human Serum | Up to Month 9 | 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. |
| Number of Participants With Any AEs, Any Serious Adverse Events and Death | Up to 9 months | 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. |
| Mean Change From Baseline in Temperature | From Baseline (D 0) to D1 and D15 of M7, M8 | — |
Countries
United States
Participant flow
Recruitment details
This study was conducted in the United States from 27 February 2007 to 01 January 2008. The study was prematurely terminated during enrolment due to legal reasons.
Pre-assignment details
A total of 80 participants were randomized, of which 78 participants received the study drug and 2 participants did not receive the study drug nor had post baseline safety assessments.
Participants by arm
| Arm | Count |
|---|---|
| RO0503821 Eligible participants were 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) was based upon the dose of epoetin alfa received 1 to 2 weeks prior to administration of study drug, while subsequent doses were 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 continued to do so. | 38 |
| Epoetin Alfa Eligible participants were administered epoetin alfa SC as per the standard of care for eight months (TP and EP), and were followed-up for 15 days following the final study visit. Participants who self-administered/visited to clinics for ESA dosing prior to randomization continued to do so. | 40 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative/Other | 27 | 33 |
| Overall Study | Adverse Event | 4 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lack of Efficacy | 2 | 0 |
| Overall Study | Protocol Violation | 2 | 3 |
| Overall Study | Withdrew consent | 1 | 2 |
Baseline characteristics
| Characteristic | RO0503821 | Epoetin Alfa | Total |
|---|---|---|---|
| Age, Continuous | 58.5 Years STANDARD_DEVIATION 12.59 | 53.6 Years STANDARD_DEVIATION 15.86 | 56.0 Years STANDARD_DEVIATION 14.48 |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Male | 20 Participants | 20 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 38 | 15 / 40 |
| serious Total, serious adverse events | 11 / 38 | 2 / 40 |
Outcome results
Primary
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.
Time frame: From Baseline (D 0) to 9 months
Population: Per-protocol population included all randomized participants who received at least one dose of the study drug and met all study entry criteria with no major protocol violations. Participants with available data at the time of evaluation were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Hb Concentration to Average Over the Evaluation Period | -0.32 g/dL | Standard Deviation 1.31 |
| Epoetin Alfa | Mean Change From Baseline in Hb Concentration to Average Over the Evaluation Period | 0.51 g/dL | Standard Deviation 1.33 |
Secondary
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.
Time frame: From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Ferritin | M4 ( n = 21,22) | 48 microgram per litre | Standard Deviation 319.7 |
| RO0503821 | Mean Change From Baseline in Ferritin | M6 (n = 12, 9) | 86 microgram per litre | Standard Deviation 226.1 |
| RO0503821 | Mean Change From Baseline in Ferritin | M3 (n = 28, 27) | 83 microgram per litre | Standard Deviation 195.1 |
| RO0503821 | Mean Change From Baseline in Ferritin | M7 (n = 7, 6) | 55 microgram per litre | Standard Deviation 117.1 |
| RO0503821 | Mean Change From Baseline in Ferritin | M5 (n = 17, 16) | 85 microgram per litre | Standard Deviation 242 |
| RO0503821 | Mean Change From Baseline in Ferritin | M8 (n = 2, 3) | -59 microgram per litre | Standard Deviation 176.8 |
| RO0503821 | Mean Change From Baseline in Ferritin | M2 (n = 32, 29) | 59 microgram per litre | Standard Deviation 128.8 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M8 (n = 2, 3) | -99 microgram per litre | Standard Deviation 36.8 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M2 (n = 32, 29) | -1 microgram per litre | Standard Deviation 129.5 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M3 (n = 28, 27) | -37 microgram per litre | Standard Deviation 114.2 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M4 ( n = 21,22) | -24 microgram per litre | Standard Deviation 155.4 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M5 (n = 17, 16) | -70 microgram per litre | Standard Deviation 149.6 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M6 (n = 12, 9) | -105 microgram per litre | Standard Deviation 187.8 |
| Epoetin Alfa | Mean Change From Baseline in Ferritin | M7 (n = 7, 6) | -120 microgram per litre | Standard Deviation 166.3 |
Secondary
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.
Time frame: From Baseline (D 0) to Month (M) 2, M3, M4, M5, M6, M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Iron | M4 ( n = 22,24) | 2.0 micromole per litre | Standard Deviation 6.97 |
| RO0503821 | Mean Change From Baseline in Iron | M6 (n = 13, 10) | 2.9 micromole per litre | Standard Deviation 8.33 |
| RO0503821 | Mean Change From Baseline in Iron | M3 (n = 29, 29) | 3.9 micromole per litre | Standard Deviation 5.39 |
| RO0503821 | Mean Change From Baseline in Iron | M7 (n = 8, 6) | 3.4 micromole per litre | Standard Deviation 5.94 |
| RO0503821 | Mean Change From Baseline in Iron | M5 (n = 18, 17) | 3.1 micromole per litre | Standard Deviation 7.66 |
| RO0503821 | Mean Change From Baseline in Iron | M8 (n = 2, 3) | 11.0 micromole per litre | Standard Deviation 13.8 |
| RO0503821 | Mean Change From Baseline in Iron | M2 (n = 33, 31) | 3.4 micromole per litre | Standard Deviation 7.25 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M8 (n = 2, 3) | 7.7 micromole per litre | Standard Deviation 13.8 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M2 (n = 33, 31) | 1.8 micromole per litre | Standard Deviation 5.07 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M3 (n = 29, 29) | -1.3 micromole per litre | Standard Deviation 5.87 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M4 ( n = 22,24) | 0.2 micromole per litre | Standard Deviation 3.26 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M5 (n = 18, 17) | 0.9 micromole per litre | Standard Deviation 2.54 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M6 (n = 13, 10) | 0.6 micromole per litre | Standard Deviation 3.94 |
| Epoetin Alfa | Mean Change From Baseline in Iron | M7 (n = 8, 6) | -1.3 micromole per litre | Standard Deviation 4.84 |
Secondary
Mean Change From Baseline in Pulse Rate
Time frame: From Baseline (D 0) to D1 and D15 of M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Pulse Rate | M7 D1 (n = 9, 6) | -2 Beats per minute | Standard Deviation 11 |
| RO0503821 | Mean Change From Baseline in Pulse Rate | M7 D15 (n = 5, 3) | 1 Beats per minute | Standard Deviation 13.3 |
| RO0503821 | Mean Change From Baseline in Pulse Rate | M8 D1 (n = 2, 3) | -7 Beats per minute | Standard Deviation 0 |
| RO0503821 | Mean Change From Baseline in Pulse Rate | M8 D15 (n = 2, 2) | -4 Beats per minute | Standard Deviation 3.5 |
| Epoetin Alfa | Mean Change From Baseline in Pulse Rate | M8 D15 (n = 2, 2) | 7 Beats per minute | Standard Deviation 6.4 |
| Epoetin Alfa | Mean Change From Baseline in Pulse Rate | M7 D1 (n = 9, 6) | -2 Beats per minute | Standard Deviation 10.6 |
| Epoetin Alfa | Mean Change From Baseline in Pulse Rate | M8 D1 (n = 2, 3) | 2 Beats per minute | Standard Deviation 4.4 |
| Epoetin Alfa | Mean Change From Baseline in Pulse Rate | M7 D15 (n = 5, 3) | 3 Beats per minute | Standard Deviation 3.1 |
Secondary
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.
Time frame: From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M4 ( n = 8, 14) | 7.25 milligram (mg) per dL | Standard Deviation 16.02 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M6 (n = 6, 6) | 10.50 milligram (mg) per dL | Standard Deviation 27.19 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M3 (n = 12,15) | -0.25 milligram (mg) per dL | Standard Deviation 24.68 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M7 (n = 4, 5) | 2.50 milligram (mg) per dL | Standard Deviation 24.06 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M5 (n = 9, 11) | 9.89 milligram (mg) per dL | Standard Deviation 29.36 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M8 (n = 2, 2) | -15.50 milligram (mg) per dL | Standard Deviation 9.19 |
| RO0503821 | Mean Change From Baseline in Serum Transferrin | M2 (n = 15, 14) | -9.27 milligram (mg) per dL | Standard Deviation 20.38 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M8 (n = 2, 2) | -6.50 milligram (mg) per dL | Standard Deviation 12.02 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M2 (n = 15, 14) | -5.00 milligram (mg) per dL | Standard Deviation 16.06 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M3 (n = 12,15) | -7.73 milligram (mg) per dL | Standard Deviation 19.56 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M4 ( n = 8, 14) | -4.21 milligram (mg) per dL | Standard Deviation 20.75 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M5 (n = 9, 11) | -6.64 milligram (mg) per dL | Standard Deviation 23.68 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M6 (n = 6, 6) | 1.50 milligram (mg) per dL | Standard Deviation 16.84 |
| Epoetin Alfa | Mean Change From Baseline in Serum Transferrin | M7 (n = 4, 5) | -5.60 milligram (mg) per dL | Standard Deviation 24.3 |
Secondary
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Time frame: From Baseline (D 0) to D1 and D15 of M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M7 D1 (n = 9, 6) | 3 millimeter of mercury | Standard Deviation 18.4 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M7 D1 (n = 9, 6) | 3 millimeter of mercury | Standard Deviation 10.2 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M7 D15 (n = 5, 3) | 5 millimeter of mercury | Standard Deviation 13.3 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M7 D15 (n = 5, 3) | 1 millimeter of mercury | Standard Deviation 10.7 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M8 D1 (n = 2, 3) | 7 millimeter of mercury | Standard Deviation 12.7 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M8 D1 (n = 2, 3) | -5 millimeter of mercury | Standard Deviation 2.1 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M8 D15 (n = 2, 2) | 6 millimeter of mercury | Standard Deviation 2.8 |
| RO0503821 | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M8 D15 (n = 2, 2) | -6 millimeter of mercury | Standard Deviation 10.6 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M8 D15 (n = 2, 2) | -5 millimeter of mercury | Standard Deviation 10.6 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M7 D1 (n = 9, 6) | 9 millimeter of mercury | Standard Deviation 22.7 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M8 D1 (n = 2, 3) | 5 millimeter of mercury | Standard Deviation 19.3 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M7 D1 (n = 9, 6) | 2 millimeter of mercury | Standard Deviation 6.9 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M8 D15 (n = 2, 2) | -6 millimeter of mercury | Standard Deviation 26.9 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | SBP at M7 D15 (n = 5, 3) | -7 millimeter of mercury | Standard Deviation 14.2 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M8 D1 (n = 2, 3) | -1 millimeter of mercury | Standard Deviation 7.9 |
| Epoetin Alfa | Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure | DBP at M7 D15 (n = 5, 3) | -2 millimeter of mercury | Standard Deviation 2.5 |
Secondary
Mean Change From Baseline in Temperature
Time frame: From Baseline (D 0) to D1 and D15 of M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Temperature | M7 D1 (n = 9, 6) | -0.0 Degree Celsius | Standard Deviation 0.43 |
| RO0503821 | Mean Change From Baseline in Temperature | M7 D15 (n = 5, 3) | 0.2 Degree Celsius | Standard Deviation 0.54 |
| RO0503821 | Mean Change From Baseline in Temperature | M8 D1 (n = 2, 3) | 0.5 Degree Celsius | Standard Deviation 0.14 |
| RO0503821 | Mean Change From Baseline in Temperature | M8 D15 (n = 2, 2) | 0.1 Degree Celsius | Standard Deviation 0.21 |
| Epoetin Alfa | Mean Change From Baseline in Temperature | M8 D15 (n = 2, 2) | -0.4 Degree Celsius | Standard Deviation 0.07 |
| Epoetin Alfa | Mean Change From Baseline in Temperature | M7 D1 (n = 9, 6) | -0.3 Degree Celsius | Standard Deviation 1.03 |
| Epoetin Alfa | Mean Change From Baseline in Temperature | M8 D1 (n = 2, 3) | -0.5 Degree Celsius | Standard Deviation 0.95 |
| Epoetin Alfa | Mean Change From Baseline in Temperature | M7 D15 (n = 5, 3) | -0.7 Degree Celsius | Standard Deviation 1.44 |
Secondary
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.
Time frame: From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M4 ( n = 12, 9) | 15.17 mg per dL | Standard Deviation 41.51 |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M6 (n = 7, 4) | 9.29 mg per dL | Standard Deviation 62.96 |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M3 (n = 17,14) | -3.29 mg per dL | Standard Deviation 45.64 |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M7 (n = 4, 1) | 3.25 mg per dL | Standard Deviation 85.99 |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M5 (n = 9, 5) | 19.67 mg per dL | Standard Deviation 53.53 |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M8 (n = 0, 1) | NA mg per dL | — |
| RO0503821 | Mean Change From Baseline in Total Iron-binding Capacity | M2 (n = 18, 17) | 20.94 mg per dL | Standard Deviation 67.8 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M8 (n = 0, 1) | -43.00 mg per dL | — |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M2 (n = 18, 17) | 1.94 mg per dL | Standard Deviation 29.47 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M3 (n = 17,14) | -9.57 mg per dL | Standard Deviation 25.58 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M4 ( n = 12, 9) | 4.67 mg per dL | Standard Deviation 19.25 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M5 (n = 9, 5) | 8.60 mg per dL | Standard Deviation 7.89 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M6 (n = 7, 4) | 21.25 mg per dL | Standard Deviation 48.34 |
| Epoetin Alfa | Mean Change From Baseline in Total Iron-binding Capacity | M7 (n = 4, 1) | 3.00 mg per dL | — |
Secondary
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.
Time frame: From Baseline (D 0) to M2, M3, M4, M5, M6, M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M4 ( n = 22,24) | 4.55 Percentage of Transferrin Saturation | Standard Deviation 17.08 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M6 (n = 13, 10) | 7.07 Percentage of Transferrin Saturation | Standard Deviation 18.1 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M3 (n = 29, 29) | 8.51 Percentage of Transferrin Saturation | Standard Deviation 12.04 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M7 (n = 8, 6) | 8.59 Percentage of Transferrin Saturation | Standard Deviation 12.2 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M5 (n = 18, 17) | 5.94 Percentage of Transferrin Saturation | Standard Deviation 16.21 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M8 (n = 2, 3) | 24.13 Percentage of Transferrin Saturation | Standard Deviation 27.83 |
| RO0503821 | Mean Change From Baseline in Transferrin Saturation | M2 (n = 33, 31) | 7.10 Percentage of Transferrin Saturation | Standard Deviation 15.32 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M8 (n = 2, 3) | 15.13 Percentage of Transferrin Saturation | Standard Deviation 23.28 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M2 (n = 33, 31) | 4.08 Percentage of Transferrin Saturation | Standard Deviation 10.39 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M3 (n = 29, 29) | -2.44 Percentage of Transferrin Saturation | Standard Deviation 13.33 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M4 ( n = 22,24) | 1.36 Percentage of Transferrin Saturation | Standard Deviation 8.52 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M5 (n = 18, 17) | 3.47 Percentage of Transferrin Saturation | Standard Deviation 6.91 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M6 (n = 13, 10) | 0.39 Percentage of Transferrin Saturation | Standard Deviation 10.79 |
| Epoetin Alfa | Mean Change From Baseline in Transferrin Saturation | M7 (n = 8, 6) | -1.80 Percentage of Transferrin Saturation | Standard Deviation 10.9 |
Secondary
Mean Change From Baseline in Weight
Time frame: From Baseline (D 0) to D1 and D15 of M7, M8
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| RO0503821 | Mean Change From Baseline in Weight | M7 D1 (n = 9, 6) | 0.5 kilogram | Standard Deviation 3.56 |
| RO0503821 | Mean Change From Baseline in Weight | M7 D15 (n = 5, 3) | 1.2 kilogram | Standard Deviation 2.93 |
| RO0503821 | Mean Change From Baseline in Weight | M8 D1 (n = 2, 3) | 3.0 kilogram | Standard Deviation 4.74 |
| RO0503821 | Mean Change From Baseline in Weight | M8 D15 (n = 2, 2) | 1.5 kilogram | Standard Deviation 3.04 |
| Epoetin Alfa | Mean Change From Baseline in Weight | M8 D15 (n = 2, 2) | 2.5 kilogram | Standard Deviation 2.33 |
| Epoetin Alfa | Mean Change From Baseline in Weight | M7 D1 (n = 9, 6) | 3.2 kilogram | Standard Deviation 3.46 |
| Epoetin Alfa | Mean Change From Baseline in Weight | M8 D1 (n = 2, 3) | 1.9 kilogram | Standard Deviation 1.57 |
| Epoetin Alfa | Mean Change From Baseline in Weight | M7 D15 (n = 5, 3) | 1.1 kilogram | Standard Deviation 2.14 |
Secondary
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.
Time frame: Up to Month 9
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 | Number of Participants With Anti-erythropoietin Antibody in Human Serum | Quantifiable at Baseline | 2 Participants |
| RO0503821 | Number of Participants With Anti-erythropoietin Antibody in Human Serum | BLQ at Baseline | 33 Participants |
| RO0503821 | Number of Participants With Anti-erythropoietin Antibody in Human Serum | Quantifiable at M 9 final visit/early termination | 1 Participants |
| RO0503821 | Number of Participants With Anti-erythropoietin Antibody in Human Serum | BLQ at M 9 final visit/early termination | 29 Participants |
| Epoetin Alfa | Number of Participants With Anti-erythropoietin Antibody in Human Serum | BLQ at M 9 final visit/early termination | 34 Participants |
| Epoetin Alfa | Number of Participants With Anti-erythropoietin Antibody in Human Serum | Quantifiable at Baseline | 1 Participants |
| Epoetin Alfa | Number of Participants With Anti-erythropoietin Antibody in Human Serum | Quantifiable at M 9 final visit/early termination | 4 Participants |
| Epoetin Alfa | Number of Participants With Anti-erythropoietin Antibody in Human Serum | BLQ at Baseline | 37 Participants |
Secondary
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.
Time frame: Up to Month 9
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 | Number of Participants With Anti-RO0503821 Antibody in Human Serum | Quantifiable at Baseline | 0 Participants |
| RO0503821 | Number of Participants With Anti-RO0503821 Antibody in Human Serum | BLQ at Baseline | 35 Participants |
| RO0503821 | Number of Participants With Anti-RO0503821 Antibody in Human Serum | Quantifiable at M 9 final visit/early termination | 0 Participants |
| RO0503821 | Number of Participants With Anti-RO0503821 Antibody in Human Serum | BLQ at M 9 final visit/early termination | 29 Participants |
Secondary
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.
Time frame: Up to 9 months
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Any AEs | 24 Participants |
| RO0503821 | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Any SAEs | 11 Participants |
| RO0503821 | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Death | 1 Participants |
| Epoetin Alfa | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Any AEs | 23 Participants |
| Epoetin Alfa | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Any SAEs | 2 Participants |
| Epoetin Alfa | Number of Participants With Any AEs, Any Serious Adverse Events and Death | Death | 0 Participants |
Secondary
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.
Time frame: Up to Month 9
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment. Participants with available data at the time of evaluation were denoted as 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Hematocrit - Low (n = 38, 40) | 8 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Hemoglobin - Low (n = 38, 40) | 11 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Platelets - High (n = 38, 40) | 0 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Platelets - Low (n = 38, 40) | 1 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | WBCs - Low (n = 38, 40) | 0 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | AST - High (n = 37, 40) | 0 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | ALT - High (n = 38, 40) | 1 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | CPK- High (n = 37, 40) | 7 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Alkaline phosphatase - High, (n = 37, 40) | 1 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Albumin - Low (n = 38, 40) | 6 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Potassium - High (n = 38, 40) | 3 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Fasting glucose - High (n = 38, 40) | 6 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Fasting glucose - Low (n = 38, 40) | 0 Participants |
| RO0503821 | Number of Participants With Marked Laboratory Abnormalities | Phosphate - High (n = 38, 40) | 17 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Potassium - High (n = 38, 40) | 4 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Hematocrit - Low (n = 38, 40) | 3 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | CPK- High (n = 37, 40) | 3 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Hemoglobin - Low (n = 38, 40) | 3 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Fasting glucose - Low (n = 38, 40) | 1 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Platelets - High (n = 38, 40) | 1 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Alkaline phosphatase - High, (n = 37, 40) | 1 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Platelets - Low (n = 38, 40) | 0 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Fasting glucose - High (n = 38, 40) | 5 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | WBCs - Low (n = 38, 40) | 1 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Albumin - Low (n = 38, 40) | 0 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | AST - High (n = 37, 40) | 2 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | Phosphate - High (n = 38, 40) | 7 Participants |
| Epoetin Alfa | Number of Participants With Marked Laboratory Abnormalities | ALT - High (n = 38, 40) | 2 Participants |
Secondary
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.
Time frame: Up to Month 9
Population: Safety population included all participants who received at least one dose of the study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RO0503821 | Percentage of Participants With Safety-Related Hb Measures | Hb value > 13 g/dL | 34 Percentage of participants |
| RO0503821 | Percentage of Participants With Safety-Related Hb Measures | Hb value > 13.5 g/dL | 13 Percentage of participants |
| RO0503821 | Percentage of Participants With Safety-Related Hb Measures | Increase in Hb value > 2 g/dL | 24 Percentage of participants |
| RO0503821 | Percentage of Participants With Safety-Related Hb Measures | Decrease in Hb value > 2 g/dL | 16 Percentage of participants |
| Epoetin Alfa | Percentage of Participants With Safety-Related Hb Measures | Decrease in Hb value > 2 g/dL | 5 Percentage of participants |
| Epoetin Alfa | Percentage of Participants With Safety-Related Hb Measures | Hb value > 13 g/dL | 33 Percentage of participants |
| Epoetin Alfa | Percentage of Participants With Safety-Related Hb Measures | Increase in Hb value > 2 g/dL | 20 Percentage of participants |
| Epoetin Alfa | Percentage of Participants With Safety-Related Hb Measures | Hb value > 13.5 g/dL | 13 Percentage of participants |