Chronic Renal Anemia
Conditions
Brief summary
This single-arm study will assess the efficacy and safety of intravenous (IV) Mircera when administered for the maintenance of hemoglobin (Hb) levels in participants with chronic renal anemia. Individuals currently receiving maintenance treatment with epoetin alfa or darbepoetin alfa will receive monthly injections of Mircera, with the starting dose (120, 200, or 360 micrograms \[mcg\] IV injection) derived from the dose of epoetin alfa or darbepoetin alfa they were receiving in the week preceding study start.
Interventions
DRUGMethoxy polyethylene glycol-epoetin beta
Participants will receive a starting dose of 120, 200, or 360 mcg via IV injection. Thereafter, the once-monthly dose will be titrated to achieve target Hb concentrations.
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
* Adults greater than or equal to (≥) 18 years of age * Chronic renal anemia * Stable epoetin alfa or darbepoetin alfa therapy for past 2 months * Hemodialysis therapy for ≥3 months
Exclusion criteria
* Transfusion of red blood cells during previous 2 months * Poorly controlled hypertension requiring hospitalization or interruption of ESA treatment in previous 6 months * Acute or chronic bleeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and Within Target Range During the Efficacy Evaluation Period (EEP) | Weeks -4, -3, -2, -1,and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | 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 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. 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 10.5 to 12.5 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Time-Adjusted Hb From Baseline to EEP | At Weeks -4, -3, -2, -1, and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | 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 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., Baseline) Hb and the EEP average Hb was calculated and expressed in g/dL. |
| Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP | Pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The percentage of participants who maintained each single Hb measurement in the target range of 10.5 to 12.5 g/dL was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds. |
| Mean Time Spent in the Target Range for Hb During the EEP | Pre-dose (0 hours) during Weeks 18, 20, 22, and 24 | During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range of 10.5 to 12.5 g/dL was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days. |
| Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP | Weeks 0, 4, 8, 12, 16, 20, and 24 | Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the EEP (Weeks 17 to 24) on the basis of Hb levels or other modification criteria. The percentage of participants who required a dose adjustment for any reason was calculated during the DTP and EEP. |
| Number of Participants Prematurely Withdrawn From the Study to Receive Blood Transfusion | Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24 | The number of participants who were prematurely withdrawn from the study to receive a blood transfusion during treatment, including the DTP (Weeks 0 and 16) and/or EEP (Weeks 17 to 24), was reported. |
Countries
Greece
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mircera in Renal Anemia Participants with chronic renal anemia who were previously treated with ESA therapy received intravenous Mircera/CERA, every 4 weeks for a total of 24 weeks in this single-arm study. The first dose of 120, 200, or 360 mcg was based upon the dose of ESA received prior to administration of study treatment, while subsequent doses were adjusted to maintain Hb concentrations within target of 10.5 and 12.5 g/dL. | 188 |
| Total | 188 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative Reasons | 1 |
| Overall Study | Adverse Event | 5 |
| Overall Study | Death | 3 |
| Overall Study | Early Improvement | 1 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Other | 10 |
| Overall Study | Protocol Violation | 7 |
| Overall Study | Refused Treatment | 19 |
| Overall Study | Screen Failure | 6 |
Baseline characteristics
| Characteristic | Mircera in Renal Anemia |
|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 14.49 |
| Sex: Female, Male Female | 73 Participants |
| Sex: Female, Male Male | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 188 |
| serious Total, serious adverse events | 34 / 188 |
Outcome results
Primary
Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and Within Target Range During the Efficacy Evaluation Period (EEP)
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 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. 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 10.5 to 12.5 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.
Time frame: Weeks -4, -3, -2, -1,and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: Per Protocol (PP) Population: All participants who received at least one dose of Mircera/CERA and provided data for at least one follow-up assessment, and who fulfilled inclusion/exclusion criteria per study protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Maintained Average Hb Within Plus/Minus (±) 1 g/dL of Reference Hb and Within Target Range During the Efficacy Evaluation Period (EEP) | 53.7 percentage of participants |
Secondary
Mean Change in Time-Adjusted Hb From Baseline to EEP
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 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. The average Hb during the EEP was calculated per participant and assessed against the reference value. The mean change in Hb value between reference (i.e., Baseline) Hb and the EEP average Hb was calculated and expressed in g/dL.
Time frame: At Weeks -4, -3, -2, -1, and 0; pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: Intent-to-Treat (ITT) Population: All participants who received at least one dose of Mircera/CERA and provided data for at least one follow-up assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Change in Time-Adjusted Hb From Baseline to EEP | 0.0 g/dL | Standard Deviation 1.17 |
Secondary
Mean Time Spent in the Target Range for Hb During the EEP
During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with Mircera/CERA. Time spent in the target range of 10.5 to 12.5 g/dL was defined as time from first on-target Hb to time of last known on-target Hb, as collected during the EEP. Time spent in the target range was averaged among all participants and expressed in days.
Time frame: Pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: ITT Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mircera in Renal Anemia | Mean Time Spent in the Target Range for Hb During the EEP | 34 days | Standard Deviation 18.1 |
Secondary
Number of Participants Prematurely Withdrawn From the Study to Receive Blood Transfusion
The number of participants who were prematurely withdrawn from the study to receive a blood transfusion during treatment, including the DTP (Weeks 0 and 16) and/or EEP (Weeks 17 to 24), was reported.
Time frame: Continuously and at every visit from Week 0 (every week until Week 2, thereafter every 2 weeks) through Week 24
Population: All Enrolled Population: Includes all participants enrolled into the study regardless of treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Number of Participants Prematurely Withdrawn From the Study to Receive Blood Transfusion | 3 participants |
Secondary
Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP
Study drug administration occurred monthly during the DTP (Weeks 0 to 16), which began with a pre-specified dose of Mircera/CERA according to the dose of ESA administered during Week -1. Subsequent doses could be adjusted throughout the study including during the EEP (Weeks 17 to 24) on the basis of Hb levels or other modification criteria. The percentage of participants who required a dose adjustment for any reason was calculated during the DTP and EEP.
Time frame: Weeks 0, 4, 8, 12, 16, 20, and 24
Population: ITT Population; number (n) of participants who entered each treatment period was reported.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP | DTP (n=187) | 68 percentage of participants |
| Mircera in Renal Anemia | Percentage of Participants Who Required Any Dose Adjustment of Mircera/CERA During the Dose Titration Period (DTP) and EEP | EEP (n=160) | 38 percentage of participants |
Secondary
Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP
During the EEP (Weeks 17 to 24), participants provided a total of four blood samples for Hb monitoring while on treatment with CERA/Mircera. The percentage of participants who maintained each single Hb measurement in the target range of 10.5 to 12.5 g/dL was determined. The 95% CI was calculated using the Pearson-Clopper method for exact confidence bounds.
Time frame: Pre-dose (0 hours) during Weeks 18, 20, 22, and 24
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mircera in Renal Anemia | Percentage of Participants Whose Hb Remained Within Target Range Throughout the EEP | 53.7 percentage of participants |