A Study of Intravenous Mircera for the Treatment of Anemia in Dialysis Patients.

An Open Label Study of the Effect of Intravenous Mircera on Hemoglobin Levels in Anemic Patients With Chronic Kidney Disease Who Are on Dialysis, and Who Have Previously Received Epoetin Alfa or Beta or Darbepoetin Alfa Treatment.

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00413894

Enrollment

424

Registered

2006-12-20

Start date

2007-03-31

Completion date

2008-10-31

Last updated

2016-02-15

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 and safety of intravenous Mircera, administered with pre-filled syringes, for the treatment of anemia in patients with chronic kidney disease who are on dialysis, and who have previously received treatment with epoetin alfa or beta or darbepoetin alfa. Patients will receive monthly intravenous injections of Mircera, with the starting dose derived from the dose of epoetin alfa or beta or darbepoetin they were receiving in the week preceding study start. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

Interventions

DRUGmethoxy polyethylene glycol-epoetin beta [Mircera]

iv monthly, with starting dose based on previous dose of epoetin alfa or beta or darbepoetin alfa

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; * longterm hemodialysis for \>=12 weeks before screening; * baseline Hb between 10 and 13g/dL; * iv or sc maintenance epoetin alfa or beta or darbepoetin alfa therapy with same dosing interval for \>=4 weeks before screening.

Exclusion criteria

* acute or chronic bleeding within 8 weeks prior to screening; * transfusion of red blood cells within 8 weeks prior to screening; * poorly controlled hypertension necessitating interruption of erythropoetin treatment in previous 6 months; * previous treatment with Mircera.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Hb Levels Within 11.0-12.5 Grams Per Deciliter (g/dL) During Evaluation Phase	Visits 8 to 10 (Months 6 to 8)	—
Percentage of Participants With Hb Levels Within 10.0-13.0 g/dL During Evaluation Phase	Visits 8 to 10 (Months 6 to 8)	—
Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL by Dose Modifications During Evaluation Phase	Visits 8 to 10 (Months 6 to 8)	Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.
Percentage of Participants With Hemoglobin Levels Within 10.0-13.0 g/dL by Dose Modification During Evaluation Phase	Visits 8 to 10 (Months 6 to 8)	Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.

Secondary

Measure	Time frame	Description
Percentage of Participants With HbLevels Within 10.0-13.0 g/dL by Dose Modification During Screening Phase	Visits 1 to 2 (Months -2 to -1)	Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.
Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels	Visits 1 to 2 (Months -2 to -1) and Visits 8 to 10 (Months 6 to 8)	Shifts in Hb levels between Screening and Evaluation Phase were classified as follows: Category A: Participants with Hb levels in both Screening and Evaluation Phase within 10-13 g/dL; Category B: Participants who had Hb values within 10-13 g/dL during Screening but shifted outside the range during Evaluation; Category C: Participants who had Hb values outside range during Screening but shifted to stable values (at least within 10 - 13 g/dL) during Evaluation.; Category D: Participants with less than two values available during Evaluation Phase. Participants could appear in only 1 category. Participants had to have 2 or 3 values within range (depending on the number of measurements available) to be counted.
Percentage of Participants Requiring Erythrocyte Transfusions	Visits 1 to 10 (Months -2 to 8)	—
Percentage of Participants With Hb Fluctuations Within Screening Phase	Visits 1 to 2 (Months -2 to -1)	Hematology and clinical chemistry were performed partially by a central laboratory as well as by the local laboratories by means of their established methods. Normal ranges and methods as well as quality assurance certificates had to be available to the sponsor prior to the start of the study. Hb fluctuation was defined as the deviation from individual mean Hb-value within the study phase (Screening Phase) and was categorized as ≤ ±1 g/dL, \>±1.0 to ±1.5 g/dL, \>±1.5 to ±2.0 g/dL, and \>±2.0 g/dL. Percentage of participants within these deviation categories are reported for Screening Phase of the study.
Percentage of Participants With Hb Fluctuations Within Evaluation Phase	Visits 8 to 10 (Months 6 to 8)	Hb fluctuation was defined as the deviation from individual mean Hb-value within the study phase (Evaluation Phase) and was categorized as less than or equal to (≤) ±1 g/dL, greater than (\>) ±1.0 to ±1.5 g/dL, \> ±1.5 to ±2.0 g/dL, and \> ±2.0 g/dL. Percentage of participants within these deviation categories were reported for Evaluation Phase of the study.
Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL During Screening Phase	Visits 1 to 2 (Months -2 to -1)	—
Percentage of Participants With Hb Levels Within 10.0-13.0 g/dL During Screening Phase	Visits 1 to 2 (Months -2 to -1)	—
Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL by Dose Modification During Screening Phase	Visits 1 to 2 (Months -2 to -1)	Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.

Countries

Germany

Participant flow

Pre-assignment details

A total of 661 participants with renal anemia due to chronic kidney disease (CKD) were enrolled; of which, 424 participants were treated with methoxy polyethylene glycol-epoetin beta (C.E.R.A) and are included in results.

Participants by arm

Arm	Count
C.E.R.A During screening (Month -2 to -1), participants received their previous ESA (epoetin alfa/beta/delta or darbepoetin alfa) at previously applied dosing scheme. During titration (Month 1-5), participants received C.E.R.A. at a starting dose of 125 or 200 μg/month administered once monthly IV. Doses were subsequently adjusted by investigator according to participant's hemoglobin values. During evaluation (Month 6 to 8), participants received C.E.R.A once monthly administered IV at a dose decided by investigator according to participant's Hb values.	424
Total	424

Arm

Count

C.E.R.A

During screening (Month -2 to -1), participants received their previous ESA (epoetin alfa/beta/delta or darbepoetin alfa) at previously applied dosing scheme. During titration (Month 1-5), participants received C.E.R.A. at a starting dose of 125 or 200 μg/month administered once monthly IV. Doses were subsequently adjusted by investigator according to participant's hemoglobin values. During evaluation (Month 6 to 8), participants received C.E.R.A once monthly administered IV at a dose decided by investigator according to participant's Hb values.

424

Total

424

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Administrative Reasons	1
Overall Study	Adverse Event	28
Overall Study	Hb <10 grams/deciliter	12
Overall Study	Other	18
Overall Study	Protocol Violation	11
Overall Study	Withdrawal by Subject	10

Baseline characteristics

Characteristic	C.E.R.A
Age, Continuous	63.1 years STANDARD_DEVIATION 14.7
Sex: Female, Male Female	166 Participants
Sex: Female, Male Male	258 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	173 / 424
serious Total, serious adverse events	174 / 424

Outcome results

Primary

Percentage of Participants With Hb Levels Within 10.0-13.0 g/dL During Evaluation Phase

Time frame: Visits 8 to 10 (Months 6 to 8)

Population: CP

Arm	Measure	Value (NUMBER)
C.E.R.A	Percentage of Participants With Hb Levels Within 10.0-13.0 g/dL During Evaluation Phase	75.6 percentage of participants

Primary

Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL by Dose Modifications During Evaluation Phase

Dose adjustment included increase or decrease in dose. Percentage of participants with Hb levels within 11.0-12.5 g/dL by dose adjustment categories (with dose adjustment and without dose adjustment) were reported.

Time frame: Visits 8 to 10 (Months 6 to 8)

Population: CP; number (n) equals (=) number of participants in the specified category

Arm	Measure	Group	Value (NUMBER)
C.E.R.A	Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL by Dose Modifications During Evaluation Phase	Without Dose Modification (n=178)	44.9 percentage of participants
C.E.R.A	Percentage of Participants With Hb Levels Within 11.0-12.5 g/dL by Dose Modifications During Evaluation Phase	With Dose Modification (n=166)	17.5 percentage of participants

Primary

Percentage of Participants With Hb Levels Within 11.0-12.5 Grams Per Deciliter (g/dL) During Evaluation Phase

Time frame: Visits 8 to 10 (Months 6 to 8)

Population: Completer Population (CP) included only participants who completed the study until Visit 10 (Month 8).

Arm	Measure	Value (NUMBER)
C.E.R.A	Percentage of Participants With Hb Levels Within 11.0-12.5 Grams Per Deciliter (g/dL) During Evaluation Phase	31.7 percentage of participants

Primary

Percentage of Participants With Hemoglobin Levels Within 10.0-13.0 g/dL by Dose Modification During Evaluation Phase

Time frame: Visits 8 to 10 (Months 6 to 8)

Population: CP; n = number of participants in the specified category

Arm	Measure	Group	Value (NUMBER)
C.E.R.A	Percentage of Participants With Hemoglobin Levels Within 10.0-13.0 g/dL by Dose Modification During Evaluation Phase	Without Dose Modification (n=178)	88.8 percentage of participants
C.E.R.A	Percentage of Participants With Hemoglobin Levels Within 10.0-13.0 g/dL by Dose Modification During Evaluation Phase	With Dose Modification (n=166)	61.5 percentage of participants

Secondary

Percentage of Participants Requiring Erythrocyte Transfusions

Time frame: Visits 1 to 10 (Months -2 to 8)

Population: Safety Population (SAF): All participants who received at least one dose of study medication independent from whether they completed the study or not were included into the safety analysis.

Arm	Measure	Group	Value (NUMBER)
C.E.R.A	Percentage of Participants Requiring Erythrocyte Transfusions	During Screening Phase	0.7 percentage of participants
C.E.R.A	Percentage of Participants Requiring Erythrocyte Transfusions	During Titration or Evaluation Phase	5.0 percentage of participants

Secondary

Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels

Shifts in Hb levels between Screening and Evaluation Phase were classified as follows: Category A: Participants with Hb levels in both Screening and Evaluation Phase within 10-13 g/dL; Category B: Participants who had Hb values within 10-13 g/dL during Screening but shifted outside the range during Evaluation; Category C: Participants who had Hb values outside range during Screening but shifted to stable values (at least within 10 - 13 g/dL) during Evaluation.; Category D: Participants with less than two values available during Evaluation Phase. Participants could appear in only 1 category. Participants had to have 2 or 3 values within range (depending on the number of measurements available) to be counted.

Time frame: Visits 1 to 2 (Months -2 to -1) and Visits 8 to 10 (Months 6 to 8)

Population: ITT Population;

Arm	Measure	Group	Value (NUMBER)
C.E.R.A	Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels	Category C	4.3 percentage of participants
C.E.R.A	Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels	Category D	14.9 percentage of participants
C.E.R.A	Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels	Category A	59.4 percentage of participants
C.E.R.A	Percentage of Participants With Changes Between Screening and Evaluation Phase With Respect To Hb Levels	Category B	19.5 percentage of participants

Secondary

Percentage of Participants With Hb Fluctuations Within Evaluation Phase

Hb fluctuation was defined as the deviation from individual mean Hb-value within the study phase (Evaluation Phase) and was categorized as less than or equal to (≤) ±1 g/dL, greater than (\>) ±1.0 to ±1.5 g/dL, \> ±1.5 to ±2.0 g/dL, and \> ±2.0 g/dL. Percentage of participants within these deviation categories were reported for Evaluation Phase of the study.

Time frame: Visits 8 to 10 (Months 6 to 8)

Population: ITT population

Arm	Measure	Group	Value (NUMBER)
C.E.R.A	Percentage of Participants With Hb Fluctuations Within Evaluation Phase	≤ ± 1.0 g/dl	82.9 percentage of participants
C.E.R.A	Percentage of Participants With Hb Fluctuations Within Evaluation Phase	> ± 1.0 to ± 1.5 g/d	7.9 percentage of participants
C.E.R.A	Percentage of Participants With Hb Fluctuations Within Evaluation Phase	> ± 1.5 to ± 2.0 g/dl	2.9 percentage of participants
C.E.R.A	Percentage of Participants With Hb Fluctuations Within Evaluation Phase	> ± 2.0 g/dl	0.5 percentage of participants
C.E.R.A	Percentage of Participants With Hb Fluctuations Within Evaluation Phase	Missing	5.8 percentage of participants

Secondary

Percentage of Participants With Hb Fluctuations Within Screening Phase

Hematology and clinical chemistry were performed partially by a central laboratory as well as by the local laboratories by means of their established methods. Normal ranges and methods as well as quality assurance certificates had to be available to the sponsor prior to the start of the study. Hb fluctuation was defined as the deviation from individual mean Hb-value within the study phase (Screening Phase) and was categorized as ≤ ±1 g/dL, \>±1.0 to ±1.5 g/dL, \>±1.5 to ±2.0 g/dL, and \>±2.0 g/dL. Percentage of participants within these deviation categories are reported for Screening Phase of the study.