Anemia
Conditions
Brief summary
This single arm study will assess the efficacy and safety of subcutaneous methoxy polyethylene glycol-epoetin beta (Mircera) for the correction and maintenance of hemoglobin levels in predialysis patients with renal anemia who are not currently treated with erythropoietin stimulating agents (ESA). Eligible patients will receive monthly subcutaneous injections of Mircera at an initial recommended dose of 1.2 micrograms/kg. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]
sc every month (starting dose 1.2 micrograms/kg)
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
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 renal anemia; * predialysis stage; * no ESA therapy during previous 3 months.
Exclusion criteria
* transfusion of red blood cells during previous 2 months; * poorly controlled hypertension requiring hospitalization in previous 6 months; * significant acute or chronic bleeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period | From Baseline (Week 0) to EEP (Week 29 to Week 36) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Whose Hb Concentrations Remained Within the Target Range of 10.0- 12.0 g/dLThroughout the EEP | From Week 29 to Week 36 | The percentage of participants whose Hb Concentrations remained within the target range of 10.0- 12.0 g/dL throughout the EEP (Week 29 to Week 36) is presented. |
| Mean Time Spent by Participants in the Target Range of 10.0- 12.0 g/dL During the EEP | From Week 29 to Week 36 | Mean time spent by participants in the target range of 10.0- 12.0 g/dL during the EEP (Week 29 to Week 36) is presented. |
| Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Weeks 0 to Week 36 | Percentage of participants requiring dose adjustments during dose titration period (DTP \[Week 0 to Week 28\]) and EEP (Week 29 to Week 36) is presented. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either ≥ 13 g/dL or \< 9 g/dL; if the difference of 2 consecutive Hb concentrations was ≥2 g/dL; if the values of scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of range of 10 to 12 g/dL; if the values of the scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of the range 10.5 to 11.5 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted. |
| Number of Participants Who Received Red Blood Cell Transfusions During the Study Period | Up to Week 52 | Red blood cell transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP (Week 0 to Week 28), EEP (Week 29 to Week 36), and during the long term safety period (LSTP \[Week 37 to Week 52\]) are presented. |
| Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Up to Week 52 | An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect. |
| Mean Change From Baseline in Hb Concentration Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in Hb concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Hematocrit Level Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in hematocrit level was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, and 48 | Mean change from Baseline in erythrocyte mean corpuscular volume was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Time to Achievement of Response During the EEP | From Week 29 to Week 36 | Participants with Hb concentrations within target range of 10-12 g/dl were considered to be responders. Mean time to achievement of response during the EEP (Week 29 to Week 36) is presented. |
| Mean Change From Baseline in Albumin Concentration Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in albumin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in C-Reactive Protein concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in phosphate and potassium concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in total iron binding capacity (TIBC) and iron concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Creatinine Concentration Over Time | Baseline (Week 0), Weeks 8, 16, 32, 40 | Mean change from Baseline in creatinine concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Ferritin Concentration Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in ferritin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in Transferrin Saturation Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in transferrin saturation (TSAT) was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
| Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48 | Mean change from Baseline in white blood cells (WBCs) and platelets concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48. |
Countries
Turkey (Türkiye)
Participant flow
Recruitment details
A total of 75 participants were enrolled in this study conducted from 12 August 2008 to December 2010 at 9 centers in Turkey.
Participants by arm
| Arm | Count |
|---|---|
| C.E.R.A Eligible participants were administered C.E.R.A subcutaneously, every 4 weeks for 44 weeks. The initial dose of C.E.R.A. was 1.2 mcg/kg. Subsequent doses were adjusted to maintain the individual participant's Hb within the target range of 10.0 and 12.0 g/dL. | 75 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative reasons | 1 |
| Overall Study | Adverse Event | 14 |
| Overall Study | Dialysis initiation | 1 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Renal transplantation | 1 |
Baseline characteristics
| Characteristic | C.E.R.A |
|---|---|
| Age, Continuous | 52.8 years STANDARD_DEVIATION 16.36 |
| Sex: Female, Male Female | 57 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 38 / 75 |
| serious Total, serious adverse events | 24 / 75 |
Outcome results
Primary
Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period
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.
Time frame: From Baseline (Week 0) to EEP (Week 29 to Week 36)
Population: Per protocol (PP) population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants with less than three recorded Hb values during EEP; missing administration of C.E.R.A. during weeks 28-36; having inadequate iron status, were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A | Mean Change in Hb Concentration Between Baseline and the Efficacy Evaluation Period | 1.99 g/dL | Standard Deviation 0.74 |
Secondary
Mean Change From Baseline in Albumin Concentration Over Time
Mean change from Baseline in albumin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 8 (n = 62) | 0.45 g/L | Standard Deviation 3.12 |
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 16 (n = 52) | 0.06 g/L | Standard Deviation 3.27 |
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 24 (n = 53) | -0.30 g/L | Standard Deviation 3.59 |
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 32 (n = 48) | 0.24 g/L | Standard Deviation 5.37 |
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 40 (n = 45) | -0.57 g/L | Standard Deviation 3.34 |
| C.E.R.A | Mean Change From Baseline in Albumin Concentration Over Time | Week 48 (n = 46) | -0.61 g/L | Standard Deviation 3.82 |
Secondary
Mean Change From Baseline in C-Reactive Protein Concentration Over Time
Mean change from Baseline in C-Reactive Protein concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 8 (n = 55) | -1.82 Milligrams /L | Standard Deviation 13.24 |
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 16 (n = 44) | -1.80 Milligrams /L | Standard Deviation 13.05 |
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 24 (n = 45) | 0.03 Milligrams /L | Standard Deviation 9.31 |
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 32 (n = 38) | -0.33 Milligrams /L | Standard Deviation 9.88 |
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 40 (n = 42) | -1.49 Milligrams /L | Standard Deviation 4.78 |
| C.E.R.A | Mean Change From Baseline in C-Reactive Protein Concentration Over Time | Week 48 (n = 39) | 0.86 Milligrams /L | Standard Deviation 6.57 |
Secondary
Mean Change From Baseline in Creatinine Concentration Over Time
Mean change from Baseline in creatinine concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 32, 40
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Creatinine Concentration Over Time | Week 8 (n = 4) | 23.87 Micromole/L |
| C.E.R.A | Mean Change From Baseline in Creatinine Concentration Over Time | Week 16 (n = 2) | 123.67 Micromole/L |
| C.E.R.A | Mean Change From Baseline in Creatinine Concentration Over Time | Week 32 (n = 2) | -8.40 Micromole/L |
| C.E.R.A | Mean Change From Baseline in Creatinine Concentration Over Time | Week 40 (n = 1) | 17.7 Micromole/L |
Secondary
Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time
Mean change from Baseline in erythrocyte mean corpuscular volume was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Week 8 (n = 65) | 0.17 Femtoliters | Standard Deviation 3.2 |
| C.E.R.A | Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Week 16 (n = 57) | -1.31 Femtoliters | Standard Deviation 3.7 |
| C.E.R.A | Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Week 24 (n = 55) | -1.10 Femtoliters | Standard Deviation 4.4 |
| C.E.R.A | Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Week 32 (n = 52) | -0.34 Femtoliters | Standard Deviation 4.62 |
| C.E.R.A | Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume Over Time | Week 48 (n = 47) | 0.97 Femtoliters | Standard Deviation 3.67 |
Secondary
Mean Change From Baseline in Ferritin Concentration Over Time
Mean change from Baseline in ferritin concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 8 (n = 52) | -95.15 mcg/L | Standard Deviation 86.09 |
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 16 (n = 49) | -82.82 mcg/L | Standard Deviation 115.68 |
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 24 (n = 42) | -71.98 mcg/L | Standard Deviation 131.47 |
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 32 (n = 39) | -78.45 mcg/L | Standard Deviation 121.12 |
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 40 (n = 42) | -59.94 mcg/L | Standard Deviation 141.89 |
| C.E.R.A | Mean Change From Baseline in Ferritin Concentration Over Time | Ferritin at Week 48 (n = 43) | -43.46 mcg/L | Standard Deviation 146.58 |
Secondary
Mean Change From Baseline in Hb Concentration Over Time
Mean change from Baseline in Hb concentration was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 8 (n = 70) | 1.50 g/dL | Standard Deviation 0.96 |
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 16 (n = 62) | 2.03 g/dL | Standard Deviation 1.16 |
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 24 (n = 59) | 1.86 g/dL | Standard Deviation 1.01 |
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 32 (n = 55) | 1.85 g/dL | Standard Deviation 0.84 |
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 40 (n = 52) | 1.84 g/dL | Standard Deviation 1.06 |
| C.E.R.A | Mean Change From Baseline in Hb Concentration Over Time | Week 48 (n = 48) | 1.59 g/dL | Standard Deviation 0.81 |
Secondary
Mean Change From Baseline in Hematocrit Level Over Time
Mean change from Baseline in hematocrit level was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 8 (n = 70) | 0.05 Fraction | Standard Deviation 0.03 |
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 16 (n = 62) | 0.06 Fraction | Standard Deviation 0.04 |
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 24 (n = 59) | 0.06 Fraction | Standard Deviation 0.03 |
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 32 (n = 55) | 0.06 Fraction | Standard Deviation 0.03 |
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 40 (n = 51) | 0.06 Fraction | Standard Deviation 0.03 |
| C.E.R.A | Mean Change From Baseline in Hematocrit Level Over Time | Week 48 (n = 49) | 0.05 Fraction | Standard Deviation 0.02 |
Secondary
Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time
Mean change from Baseline in phosphate and potassium concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 8 (n = 59) | 0.11 Millimoles /L | Standard Deviation 0.35 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 16 (n = 48) | 0.06 Millimoles /L | Standard Deviation 0.26 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 24 (n = 51) | 0.07 Millimoles /L | Standard Deviation 0.36 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 32 (n = 45) | 0.13 Millimoles /L | Standard Deviation 0.27 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 40 (n = 44) | 0.06 Millimoles /L | Standard Deviation 0.31 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Phosphate at Week 48 (n = 43) | 0.07 Millimoles /L | Standard Deviation 0.3 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 8 (n = 63) | 0.12 Millimoles /L | Standard Deviation 0.53 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 16 (n = 54) | 0.03 Millimoles /L | Standard Deviation 0.68 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 24 (n = 53) | 0.02 Millimoles /L | Standard Deviation 0.56 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 32 (n = 49) | -0.04 Millimoles /L | Standard Deviation 0.63 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 40 (n = 46) | 0.16 Millimoles /L | Standard Deviation 0.56 |
| C.E.R.A | Mean Change From Baseline in Phosphate and Potassium Concentrations Over Time | Potassium at Week 48 (n = 47) | 0.03 Millimoles /L | Standard Deviation 0.7 |
Secondary
Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time
Mean change from Baseline in total iron binding capacity (TIBC) and iron concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 8 (n = 62) | 0.09 Micromole /L | Standard Deviation 10.02 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 16 (n = 53) | -0.21 Micromole /L | Standard Deviation 8.12 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 24 (n = 52) | 0.34 Micromole /L | Standard Deviation 10.78 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 32 (n = 47) | 0.15 Micromole /L | Standard Deviation 10.53 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 40 (n = 45) | 2.24 Micromole /L | Standard Deviation 19.75 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | TIBC at Week 48 (n = 46) | -2.02 Micromole /L | Standard Deviation 11.05 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 8 (n = 63) | -1.93 Micromole /L | Standard Deviation 7.31 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 16 (n = 53) | 0.31 Micromole /L | Standard Deviation 6.79 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 24 (n = 54) | 0.55 Micromole /L | Standard Deviation 8.56 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 32 (n = 47) | 0.68 Micromole /L | Standard Deviation 8.64 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 40 (n = 45) | 1.64 Micromole /L | Standard Deviation 6.76 |
| C.E.R.A | Mean Change From Baseline in Total Iron Binding Capacity and Iron Concentrations Over Time | Iron at Week 48 (n = 46) | 0.80 Micromole /L | Standard Deviation 9.24 |
Secondary
Mean Change From Baseline in Transferrin Saturation Over Time
Mean change from Baseline in transferrin saturation (TSAT) was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 8 (n = 62) | -5.91 Percentage of Transferrin Saturation | Standard Deviation 19.83 |
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 16 (n = 52) | 1.69 Percentage of Transferrin Saturation | Standard Deviation 13.85 |
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 24 (n = 51) | 1.42 Percentage of Transferrin Saturation | Standard Deviation 15.15 |
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 32 (n = 47) | 2.52 Percentage of Transferrin Saturation | Standard Deviation 15.7 |
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 40 (n = 45) | 3.52 Percentage of Transferrin Saturation | Standard Deviation 13.02 |
| C.E.R.A | Mean Change From Baseline in Transferrin Saturation Over Time | TSAT at Week 48 (n = 46) | 5.32 Percentage of Transferrin Saturation | Standard Deviation 21.6 |
Secondary
Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time
Mean change from Baseline in white blood cells (WBCs) and platelets concentrations was calculated as the difference between Baseline and post-baseline measurements. It was recorded for each participant at enrollment (Week 0) and at different time points during the study up to Week 48.
Time frame: Baseline (Week 0), Weeks 8, 16, 24, 32, 40, and 48
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants analyzed at a particular visit is determined by 'n'.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 8 (n = 66) | 0.04 10^9 cells/Liter (L) | Standard Deviation 1.59 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 16 (n = 58) | 0.06 10^9 cells/Liter (L) | Standard Deviation 1.36 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 24 (n = 55) | 0.12 10^9 cells/Liter (L) | Standard Deviation 1.46 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 32 (n = 52) | 0.01 10^9 cells/Liter (L) | Standard Deviation 1.48 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 40 (n = 47) | -0.13 10^9 cells/Liter (L) | Standard Deviation 1.54 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | WBCs at Week 48 (n = 47) | 0.04 10^9 cells/Liter (L) | Standard Deviation 1.43 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 8 (n = 66) | -8.39 10^9 cells/Liter (L) | Standard Deviation 52.64 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 16 (n = 58) | -15.73 10^9 cells/Liter (L) | Standard Deviation 46.37 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 24 (n = 55) | -20.55 10^9 cells/Liter (L) | Standard Deviation 41.59 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 32 (n = 52) | -25.34 10^9 cells/Liter (L) | Standard Deviation 47.22 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 40 (n = 47) | -25.84 10^9 cells/Liter (L) | Standard Deviation 46.9 |
| C.E.R.A | Mean Change From Baseline in White Blood Cells and Platelets Concentrations Over Time | Platelets at Week 48 (n = 47) | -23.40 10^9 cells/Liter (L) | Standard Deviation 40.74 |
Secondary
Mean Time Spent by Participants in the Target Range of 10.0- 12.0 g/dL During the EEP
Mean time spent by participants in the target range of 10.0- 12.0 g/dL during the EEP (Week 29 to Week 36) is presented.
Time frame: From Week 29 to Week 36
Population: PP population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants with less than three recorded Hb values during EEP; missing administration of C.E.R.A. during weeks 28-36; having inadequate iron status, were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A | Mean Time Spent by Participants in the Target Range of 10.0- 12.0 g/dL During the EEP | 40.6 Days | Standard Deviation 16.31 |
Secondary
Mean Time to Achievement of Response During the EEP
Participants with Hb concentrations within target range of 10-12 g/dl were considered to be responders. Mean time to achievement of response during the EEP (Week 29 to Week 36) is presented.
Time frame: From Week 29 to Week 36
Population: PP population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants with less than three recorded Hb values during EEP; missing administration of C.E.R.A. during weeks 28-36; having inadequate iron status, were excluded.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| C.E.R.A | Mean Time to Achievement of Response During the EEP | 24.2 Days | Standard Deviation 20.96 |
Secondary
Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be 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. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time frame: Up to Week 52
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Any AEs | 58 Participants |
| C.E.R.A | Number of Participants Who Experienced Any Adverse Events or Serious Adverse Events | Any SAEs | 24 Participants |
Secondary
Number of Participants Who Received Red Blood Cell Transfusions During the Study Period
Red blood cell transfusions were given during the treatment period in case of medical need. Blood transfusions occurred during the DTP (Week 0 to Week 28), EEP (Week 29 to Week 36), and during the long term safety period (LSTP \[Week 37 to Week 52\]) are presented.
Time frame: Up to Week 52
Population: Safety population included all participants who received at least one dose of the trial medication and underwent a safety follow-up, whether withdrawn prematurely or not. Number of participants who entered a particular phase is determined by 'n'.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A | Number of Participants Who Received Red Blood Cell Transfusions During the Study Period | DTP (n = 75) | 2 Number of participants |
| C.E.R.A | Number of Participants Who Received Red Blood Cell Transfusions During the Study Period | EEP (n = 57) | 1 Number of participants |
| C.E.R.A | Number of Participants Who Received Red Blood Cell Transfusions During the Study Period | LSTP (n = 54) | 1 Number of participants |
Secondary
Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP
Percentage of participants requiring dose adjustments during dose titration period (DTP \[Week 0 to Week 28\]) and EEP (Week 29 to Week 36) is presented. The dose adjustments (increase or decrease) were required: if a single Hb concentration was either ≥ 13 g/dL or \< 9 g/dL; if the difference of 2 consecutive Hb concentrations was ≥2 g/dL; if the values of scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of range of 10 to 12 g/dL; if the values of the scheduled Hb assessments on the day of administration of C.E.R.A. and on the previous study visit were both out of the range 10.5 to 11.5 g/dL. Dose adjustment could be made at any time at the discretion of the clinician if clinically warranted.
Time frame: Weeks 0 to Week 36
Population: PP population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up. Participants with less than three recorded Hb values during EEP; missing administration of C.E.R.A. during weeks 28-36; having inadequate iron status, were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Any dose adjustment in DTP | 85.4 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose increased in DTP | 14.6 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose decreased in DTP | 24.4 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose increased and decreased in DTP | 46.3 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Any dose adjustment in EEP | 56.1 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose increased in EEP | 17.1 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose decreased in EEP | 31.7 Percentage of participants |
| C.E.R.A | Percentage of Participants Requiring Dose Adjustments During Dose Titration Period and EEP | Dose increased and decreased in EEP | 7.3 Percentage of participants |
Secondary
The Percentage of Participants Whose Hb Concentrations Remained Within the Target Range of 10.0- 12.0 g/dLThroughout the EEP
The percentage of participants whose Hb Concentrations remained within the target range of 10.0- 12.0 g/dL throughout the EEP (Week 29 to Week 36) is presented.
Time frame: From Week 29 to Week 36
Population: PP population included all participants who received at least one dose of C.E.R.A. and had at least one follow-up variable were included. Participants with less than three recorded Hb values during EEP; participants missing administration of C.E.R.A. during weeks 28-36; participants with inadequate iron status, were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| C.E.R.A | The Percentage of Participants Whose Hb Concentrations Remained Within the Target Range of 10.0- 12.0 g/dLThroughout the EEP | 43.9 Percentage of participants |