A Study of Intravenous Mircera in Hemodialysis Patients With Chronic Renal Anemia

A Single Arm Open Label Study to Assess the Efficacy, Safety and Tolerability of Once-monthly Administration of Intravenous C.E.R.A. for the Maintenance of Haemoglobin Levels in Haemodialysis Patients With Chronic Renal Anaemia.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00661505

Enrollment

132

Registered

2008-04-18

Start date

2008-05-14

Completion date

2010-06-22

Last updated

2017-12-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anemia

Brief summary

This single arm study will assess the efficacy, safety and tolerability of once-monthly administration of intravenous Mircera for the maintenance of hemoglobin levels in hemodialysis patients with chronic renal anemia. Patients will receive 4-weekly intravenous injections of Mircera, at a starting dose of 120, 200 or 360 micrograms. 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

120, 200 or 360 micrograms iv every 4 weeks (starting dose)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* adult patients, \>= 18 years of age; * chronic renal anemia; * continuous stable iv or sc maintenance epoetin therapy during previous 4 weeks; * regular long-term hemodialysis therapy with the same mode of dialysis for previous 3 months.

Exclusion criteria

* transfusion of red blood cells during previous 2 months; * poorly controlled hypertension requiring hospitalization or interruption of epoetin treatment in previous 6 months; * significant acute or chronic bleeding.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Maintained Their Mean Hemoglobin Concentration Within +/- 1.0 Gram/Deciliter of Their Reference Hemoglobin Concentration and Between 10.0 and 12.0 Gram/Deciliter During the Efficacy Evaluation Period	EEP (Week 16 to Week 24)	The reference hemoglobin (Hb) value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). The time adjusted average Hb concentration of all the values recorded during the efficacy evaluation period (EEP) was calculated for each participant and their reference Hb concentration was subtracted from this value. The percentage of participants maintaining their average Hb concentration during the EEP within +/- 1 gram/deciliter (g/dL) of their reference Hb concentration and between the Hb range 10.0 -12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. Data missing at the end of the EEP was handled using the last value carried forward method, including any data missing due to withdrawal of participants following red blood cells (RBC) transfusion.

Secondary

Measure	Time frame	Description
Percentage of Participants Maintaining Hemoglobin Concentration Within the Range of 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period	EEP (Week 16 to Week 24)	The time adjusted average Hb concentration of all the values recorded during the EEP was calculated for each participant. The percentage of participants maintaining their average Hb concentration during the EEP within the Hb concentration range of 10.0-12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24.
Median Time Spent in the Hemoglobin Range 10.0-12.0 Gram/Deciliter During the Efficacy Evaluation Period	EEP (Week 16 to Week 24)	The Hb concentration was recorded for all the participants during the EEP. The median time spent (in days) by participants in the target range (10.0-12.0 g/dL) during the EEP is presented. The EEP was defined as Week 16 to Week 24.
Mean C.E.R.A. Dose Required to Maintain Hemoglobin Level Within the Range 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period	EEP (Week 16 to Week 20)	The mean dose of C.E.R.A. required to maintain Hb level between 10.0-12.0 g/dL during the EEP was calculated per participant and then summarized. The EEP was defined as Week 16 to Week 24. However, C.E.R.A. was not administered at the Week 24 visit. Therefore, the time period for calculation of mean C.E.R.A. dose during EEP is from Week 16 to Week 20.
Percentage of Participants Requiring Any Dose Adjustments in C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period	DTP (Week 1 to Week 16), EEP (Week 16 to Week 24)	Dose adjustments were necessary when Hb increased or decreased by a clinically significant amount. The dose of C.E.R.A. was adjusted to maintain the individual participant's Hb within a range of +/- 1.0 g/dL of the reference Hb concentration and between 10.0 and 12.0 g/dL throughout the dose titration period (DTP) and the EEP (Week 1 to Week 24). The reference Hb value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0).
Mean Monthly Dose of C.E.R.A. During the Dose Titration Period and Efficacy Evaluation Period	DTP (Week 1 to Week 16), EEP (Week 16 to Week 24)	The mean monthly dose of C.E.R.A. administered during the DTP and EEP was calculated per participant and then summarized.
Mean Change From Baseline in Erythrocyte Mean Corpuscular Volume at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from Baseline in erythrocyte mean corpuscular volume (MCV) was calculated as the value at a specific week during the study minus the BL value. The Baseline was defined as Week -4 to Week 0.
Mean Change From Baseline in Hematocrit at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	The hematocrit, also called packed cell volume or erythrocyte volume fraction, is the volume percentage of red blood cells in the blood. Mean change from Baseline (BL) in hematocrit was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Hemoglobin at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in hemoglobin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Leucocytes and Platelet at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in for each parameter (leucocytes and platelet) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Ferritin at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in ferritin was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change in Hemoglobin Concentration Between the Stability Verification Period and the Efficacy Evaluation Period	SVP (Week -4 to Week 0) and EEP (Week 16 to Week 24)	The mean change in the time-adjusted average Hb concentration between the two study periods The Stability Verification Period (SVP) and EEP is presented. The SVP was defined as Week -4 to Week 0. The EEP was defined as Week 16 to Week 24.
Mean Change From Baseline in Transferrin and Albumin at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in each parameter (transferrin and albumin) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Transferrin Saturation at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in transferrin saturation (TSAT) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in C-Reactive Protein at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in C-reactive protein was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Phosphate and Potassium at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in each parameter (phosphate and potassium) was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change From Baseline in Weight at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in weight was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.
Mean Change in From Baseline in Blood Pressure at Week 16 and Week 24	Baseline (Week -4 to Week 0), Week 16, and Week 24	Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before blood sampling and C.E.R.A. administration. Blood pressure was assessed both before and after the dialysis session for participants undergoing hemodialysis. Change from BL in blood pressure was calculated as the value at a specific week (W) during the study minus the BL value. The baseline was defined as Week -4 to Week 0.
Number of Participants Taking Concomitant Medications	Up to Week 28	The number of participants taking different classes of concomitant medications at any time following enrollment into the study is presented.
Number of Participants With Any Adverse Events and Serious Adverse Events	Up to Week 28	An adverse event (AE) is any untoward medical occurrence in a participant who is 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.
Number of Participants With Reports of Anti-erythropoietin Antibodies	Up to Week 24	The number of participants with Anti-epoetin antibodies is presented.
Number of Participants Who Received Red Blood Cell Transfusions During the Dose Titration Period and Efficacy Evaluation Period	Week 1 to Week 24	Red blood cell transfusions were permitted during the DTP and EEP (Week 1 to Week 24) in case of medical need. All participants requiring a blood transfusion were withdrawn from the study. The number of participants who were administered RBC transfusions during the DTP and EEP is presented.
Mean Change From Baseline in Iron, Total Iron Binding Capacity, and Creatinine at Week 16 and Week 24	BL (Week -4 to Week 0), Week 16, and Week 24	Mean change from BL in each parameter \[iron, total iron binding capacity (TIBC), and creatinine\] was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.

Countries

Turkey (Türkiye)

Participant flow

Recruitment details

A total of 132 participants were enrolled in this study conducted from 14 May 2008 to 22 June 2010 at 20 centers in Turkey.

Participants by arm

Arm	Count
C.E.R.A. 120, 200, or 360 mcg Eligible participants were administered Continuous Erythropoietin Receptor Activator (C.E.R.A.) at a dose of 120, 200, or 360 microgram (mcg), intravenously (IV), every 4 weeks i.e. Weeks 4, 8, 12, 16 and 20 but not on Weeks 24 and 28. The initial dose of C.E.R.A.was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA). The ESA therapy was administered from enrollment to the 4 weeks stability verification period (SVP), weekly, either as epoetin (\<8000 IU, 8000-16000 IU, or \>16000 IU) or darbepoetin alpha (\<40 mcg, 40-80 mcg, or \>80 mcg). A telephone follow-up visit took place 4 weeks after the end of C.E.R.A. treatment (Week 28).	131
Total	131

Arm

Count

C.E.R.A. 120, 200, or 360 mcg

Eligible participants were administered Continuous Erythropoietin Receptor Activator (C.E.R.A.) at a dose of 120, 200, or 360 microgram (mcg), intravenously (IV), every 4 weeks i.e. Weeks 4, 8, 12, 16 and 20 but not on Weeks 24 and 28. The initial dose of C.E.R.A.was based on the last dose of the previous Erythropoiesis Stimulating Agent (ESA). The ESA therapy was administered from enrollment to the 4 weeks stability verification period (SVP), weekly, either as epoetin (\<8000 IU, 8000-16000 IU, or \>16000 IU) or darbepoetin alpha (\<40 mcg, 40-80 mcg, or \>80 mcg). A telephone follow-up visit took place 4 weeks after the end of C.E.R.A. treatment (Week 28).

131

Total

131

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Adverse Event	3
Overall Study	Lost to Follow-up	3
Overall Study	Other	2
Overall Study	Protocol Violation	14
Overall Study	Withdrawal by Subject	8

Baseline characteristics

Characteristic	C.E.R.A. 120, 200, or 360 mcg
Age, Continuous	50.4 years STANDARD_DEVIATION 13.8
Sex: Female, Male Female	65 Participants
Sex: Female, Male Male	66 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	0 / 131
serious Total, serious adverse events	13 / 131

Outcome results

Primary

Percentage of Participants Who Maintained Their Mean Hemoglobin Concentration Within +/- 1.0 Gram/Deciliter of Their Reference Hemoglobin Concentration and Between 10.0 and 12.0 Gram/Deciliter During the Efficacy Evaluation Period

The reference hemoglobin (Hb) value was taken as the time adjusted average of all Hb assessments during the SVP (Week -4 to Week 0). The time adjusted average Hb concentration of all the values recorded during the efficacy evaluation period (EEP) was calculated for each participant and their reference Hb concentration was subtracted from this value. The percentage of participants maintaining their average Hb concentration during the EEP within +/- 1 gram/deciliter (g/dL) of their reference Hb concentration and between the Hb range 10.0 -12.0 g/dL is presented. The EEP was defined as Week 16 to Week 24. Data missing at the end of the EEP was handled using the last value carried forward method, including any data missing due to withdrawal of participants following red blood cells (RBC) transfusion.

Time frame: EEP (Week 16 to Week 24)

Population: The per protocol (PP) population included all participants who received at least one dose C.E.R.A. and underwent a safety follow-up except who had \< 3 recorded Hb values and had inadequate iron status during EEP, missed C.E.R.A administration during Weeks 16-24, and/or who withdrawn before the end of EEP.

Arm	Measure	Value (NUMBER)
C.E.R.A. 120, 200, or 360 mcg	Percentage of Participants Who Maintained Their Mean Hemoglobin Concentration Within +/- 1.0 Gram/Deciliter of Their Reference Hemoglobin Concentration and Between 10.0 and 12.0 Gram/Deciliter During the Efficacy Evaluation Period	46.43 Percentage of participants

Secondary

Mean C.E.R.A. Dose Required to Maintain Hemoglobin Level Within the Range 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period

The mean dose of C.E.R.A. required to maintain Hb level between 10.0-12.0 g/dL during the EEP was calculated per participant and then summarized. The EEP was defined as Week 16 to Week 24. However, C.E.R.A. was not administered at the Week 24 visit. Therefore, the time period for calculation of mean C.E.R.A. dose during EEP is from Week 16 to Week 20.

Time frame: EEP (Week 16 to Week 20)

Population: The ITT population included participants who received at least one dose of C.E.R.A. at Week 0 and for whom data for at least one follow-up variable was available. Participants with available data at the time of assessment were included in the analysis.

Arm	Measure	Value (MEAN)	Dispersion
C.E.R.A. 120, 200, or 360 mcg	Mean C.E.R.A. Dose Required to Maintain Hemoglobin Level Within the Range 10.0-12.0 Gram/Deciliter Throughout the Efficacy Evaluation Period	103.5 mcg	Standard Deviation 46.95

Secondary

Mean Change From Baseline in C-Reactive Protein at Week 16 and Week 24

Mean change from BL in C-reactive protein was calculated as the value at a specific week during the study minus the BL value. The BL was defined as Week -4 to Week 0.