Trial Outcomes & Findings for A Study of Intravenous Mircera for the Treatment of Anemia in Dialysis Patients (NCT NCT00077610)

Last Updated: 2017-01-13

Results Overview

A time adjusted mean change in Hb concentration was calculated using an Area Under the Curve (AUC) approach, for both periods separately. Change in Hb concentration between the Baseline and evaluation periods was calculated by subtracting the calculated average baseline Hb from the average evaluation period Hb. At the end of the Week 36, data allowing the evaluation of the therapeutic response was available for 188 out of 221 eligible participants in RO0503821 (1x/2 Weeks) arm; 172 out of 220 eligible participants in RO0503821 (1x/4 Weeks); and 180 out of 225 participants in Epoetin (1-3x/Weeks) arm.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

673 participants

Primary outcome timeframe

Baseline, Week 29 to Week 36

Results posted on

2017-01-13

Participant Flow

A total of 673 participants were recruited at 91 centers in 8 countries with chronic renal anemia and dialysis therapy for at least 12 weeks before screening and during the screening/baseline period. This study was conducted between February 25, 2004 and August 17, 2005

Participant milestones

Participant milestones
Measure	RO0503821 (1x/2 Weeks) Participants received RO0503821 (Mircera \[methoxy polyethylene glycol-epoetin beta\]) once every two weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (60, 100, or 180 microgram \[mcg\]) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 International units \[IU\]/Week) administered during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (120, 200, or 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Weeks) Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Overall Study STARTED	223	224	226
Overall Study Started Treatment	221	220	225
Overall Study COMPLETED	169	168	180
Overall Study NOT COMPLETED	54	56	46

Reasons for withdrawal

Reasons for withdrawal
Measure	RO0503821 (1x/2 Weeks) Participants received RO0503821 (Mircera \[methoxy polyethylene glycol-epoetin beta\]) once every two weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (60, 100, or 180 microgram \[mcg\]) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 International units \[IU\]/Week) administered during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (120, 200, or 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Weeks) Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Overall Study Adverse Event	9	7	1
Overall Study Lost to Follow-up	0	1	2
Overall Study Withdrawal by Subject	4	10	6
Overall Study Death	17	13	13
Overall Study Renal transplant	12	15	11
Overall Study Withdrew from dialysis care	5	0	3
Overall Study Insufficient Therapeutic Response	1	0	0
Overall Study Multiple blood transfusions	0	0	1
Overall Study Principal Investigator's decision	1	0	1
Overall Study Worsening of health condition	1	1	0
Overall Study Given Epogen in hospital	1	0	0
Overall Study Transferred to other unit	0	0	1
Overall Study Transferred to nursing home	0	0	1
Overall Study Transfer to satellite unit	1	0	0
Overall Study Transfer to other center for surgery	1	0	0
Overall Study Change in dialysis modality	1	0	0
Overall Study Relocation	0	8	5
Overall Study Financial issues	0	1	0
Overall Study Sponsors decision to withdraw	0	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RO0503821 (1x/2 Weeks) n=221 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (60, 100, or 180 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=220 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants received a starting dose of RO0503821 (120, 200, or 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Weeks) n=225 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.	Total n=666 Participants Total of all reporting groups
Age, Continuous	59.2 years STANDARD_DEVIATION 15.05 • n=5 Participants	59.0 years STANDARD_DEVIATION 15.00 • n=7 Participants	58.5 years STANDARD_DEVIATION 15.16 • n=5 Participants	58.9 years STANDARD_DEVIATION 15.05 • n=4 Participants
Gender Female	89 Participants n=5 Participants	95 Participants n=7 Participants	92 Participants n=5 Participants	276 Participants n=4 Participants
Gender Male	132 Participants n=5 Participants	125 Participants n=7 Participants	133 Participants n=5 Participants	390 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 29 to Week 36

Population: The Per Protocol population included all randomized participants except those not meeting inclusion criterion related to Hb parameters and \<5 recorded Hb values during the evaluation period with missing administrations of the study drug/ reference drug. Please refer to the outcome measure description section for more details.

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=188 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=172 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=180 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Mean Change in Hemoglobin (Hb) Concentration From Baseline to Evaluation Period	-0.10 gram per deciliter (g/dL) Standard Deviation 1.06	0.01 gram per deciliter (g/dL) Standard Deviation 0.96	-0.10 gram per deciliter (g/dL) Standard Deviation 0.92

SECONDARY outcome

Timeframe: Baseline, Week 29 to Week 36

Population: The intent-to-treat (ITT) population was defined as all randomized participants. At the end of Week 36, data allowing the evaluation of the therapeutic response was available for 196/221, 188/220, and 205/225 participants in RO0503821 (1x/2 Weeks), RO0503821 (1x/4 Weeks), and Epoetin (1 -3x/Weeks), respectively.

The mean Hb of all values recorded during the evaluation period were calculated, and were subtracted from the mean baseline Hb for each participant. The number of participants maintaining their average Hb within +/- 1 g/dL of their average baseline hemoglobin concentration is given.

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=196 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=188 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=205 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Number of Participants Maintaining Average Hemoglobin Concentration During Evaluation Period Within +/- 1 Gram Per Deciliter (g/dl) of Average Baseline Hemoglobin Concentration.	133 participants	127 participants	138 participants

SECONDARY outcome

Timeframe: Week 1 to Week 36

Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not.

The number of participants who received RBC transfusions during the titration and evaluation periods were reported .

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=221 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=220 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=225 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
The Incidence of Red Blood Cell (RBC) Transfusions During the Titration and Evaluation Periods	21 participants	16 participants	17 participants

SECONDARY outcome

Timeframe: Up to Week 53

Population: The Safety Population was defined as all participants who received at least one dose of RO0503821 or Epoetin, and a safety follow-up, whether withdrawn prematurely or not. Participants available at particular time point were included in the analysis (n).

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=218 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=217 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=223 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) High Platelet (n=218, 216, 223)	0 participants	1 participants	3 participants
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) Low Platelet (n=218, 216, 223)	14 participants	10 participants	6 participants
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) High WBC (n=218, 217, 223)	0 participants	2 participants	3 participants
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) Low WBC (n=218, 217, 223)	8 participants	6 participants	5 participants
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) High RBC (n=124, 129, 89)	1 participants	2 participants	0 participants
Number of Participants With Marked Laboratory Abnormalities in Platelet, White Blood Cell Counts (WBC) and Red Blood Cells (RBC) Low RBC (n=124, 129, 89)	1 participants	2 participants	0 participants

SECONDARY outcome

Timeframe: Up to Week 53

Marked laboratory abnormalities were defined as those values that were outside the Roche marked abnormality reference range. These abnormality laboratory values were flagged as Low or High if they were below the lower limit or above the upper limit of Roche marked abnormality reference range, respectively. The marked abnormality reference range for aspartate aminotransferase (AST) was 0-80 (unit per litre \[U/L\]), alanine aminotransferase (ALT) 0-110 U/L, alkaline phosphatase (ALP) 0-220 U/L, albumin \>=30.0 gram/litre (g/L), glucose in non-diabetics 2.80-11.10 (millimol/litre \[mmol/L\]); potassium 2.90-5.80 mmol/L, and phosphorus 0.75-1.60 mmol/L

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=218 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=216 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=224 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High ALT. (n=218, 216, 224)	4 participants	2 participants	5 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High ALP (n=218, 216, 224)	15 participants	14 participants	16 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Low Albumin (n=218, 216, 224)	14 participants	13 participants	18 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High Phosphate (n=218, 216, 224)	106 participants	95 participants	94 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Low Phosphate (n=218, 216, 224)	21 participants	21 participants	17 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High Potassium (n=218, 216, 224)	33 participants	35 participants	36 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Low Potassium (n=218, 216, 224)	10 participants	3 participants	3 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High AST (n=218, 215, 224)	6 participants	3 participants	4 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes High Blood glucose in non-diabetic (n=114,131,110)	0 participants	3 participants	1 participants
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Low Blood Glucose in Non-Diabetic (n=114,131,110)	0 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Baseline, Week 36 and Week 52

Blood pressure was measured by manual assessment or automated reading throughout the entire study for every participant. Blood pressure was taken in the sitting position after at least 5 minutes rest. An appropriate -sized cuff was used and both systolic (SBP) and diastolic (DBP) blood pressures were recorded before dialysis (BD) and after dialysis (AD).

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=189 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=178 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=196 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in SBP, BD at Wk 36 (n=189, 178,196)	1 millimeter of mercury (mmHg) Standard Deviation 25.3	-2 millimeter of mercury (mmHg) Standard Deviation 22.7	3 millimeter of mercury (mmHg) Standard Deviation 25.1
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in SBP, BD at Wk 52 (n=168, 166, 180)	-0 millimeter of mercury (mmHg) Standard Deviation 24.6	-3 millimeter of mercury (mmHg) Standard Deviation 24.6	1 millimeter of mercury (mmHg) Standard Deviation 26.0
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in DBP, BD at Wk 36 (n=189, 178, 195)	0 millimeter of mercury (mmHg) Standard Deviation 14.7	-3 millimeter of mercury (mmHg) Standard Deviation 16.3	1 millimeter of mercury (mmHg) Standard Deviation 16.8
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in DBP, BD at Wk 52 (n=168, 166, 179)	1 millimeter of mercury (mmHg) Standard Deviation 15.2	-3 millimeter of mercury (mmHg) Standard Deviation 18.3	-1 millimeter of mercury (mmHg) Standard Deviation 15.4
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in SBP, AD at Wk 36 (n=189, 177, 196)	3 millimeter of mercury (mmHg) Standard Deviation 28.3	-1 millimeter of mercury (mmHg) Standard Deviation 27.0	-0 millimeter of mercury (mmHg) Standard Deviation 24.3
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in SBP, AD at Wk 52 (n=167, 168, 179)	2 millimeter of mercury (mmHg) Standard Deviation 24.5	-0 millimeter of mercury (mmHg) Standard Deviation 29.3	1 millimeter of mercury (mmHg) Standard Deviation 24.9
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in DBP, AD at Wk 36 (n=189, 177, 196)	-1 millimeter of mercury (mmHg) Standard Deviation 16.4	-0 millimeter of mercury (mmHg) Standard Deviation 15.2	-2 millimeter of mercury (mmHg) Standard Deviation 12.4
Mean Change in Blood Pressure From Baseline at Week 36 and Week 52 Change in DBP, AD at Wk 52 (n=167, 168, 178)	-1 millimeter of mercury (mmHg) Standard Deviation 14.9	-0 millimeter of mercury (mmHg) Standard Deviation 15.9	-3 millimeter of mercury (mmHg) Standard Deviation 14.9

SECONDARY outcome

Timeframe: Baseline, Week 36 and Week 52

Change in pulse rate (beats per minute \[bpm\]) from baseline values includes only those participants with both a baseline value and a value for specified time period.

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=188 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=176 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=193 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 Change from BL at Week 52 (n=168, 166, 179)	1 beats per minute (bpm) Standard Deviation 13.6	1 beats per minute (bpm) Standard Deviation 13.4	-1 beats per minute (bpm) Standard Deviation 13.2
Mean Change in Pulse Rate (Sitting) From Baseline at Week 36 and Week 52 Change from BL at Week 36 (n=188, 176, 193)	1 beats per minute (bpm) Standard Deviation 12.0	2 beats per minute (bpm) Standard Deviation 11.8	0 beats per minute (bpm) Standard Deviation 14.5

SECONDARY outcome

Timeframe: Upto Week 53

An AE is defined as 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. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is a significant medical event in the investigator's judgment or requires intervention to prevent one or other of these outcomes. Overall deaths occurred in the study were reported.

Outcome measures

Outcome measures
Measure	RO0503821 (1x/2 Weeks) n=221 Participants Participants received RO0503821 once every two weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (60, 120,180 mcg) that was based on the Epoetin dose administered (\<8000, 8000-16000, \>16000 IU/Week) during the week preceding the switch to the study drug.	RO0503821 (1x/4 Weeks) n=220 Participants Participants received RO0503821 once every four weeks intravenously for 52 weeks. Participants randomized received a starting dose of RO0503821 (120, 200, 360 mcg) that was based on the Epoetin dose (\<8000, 8000-16000, \>16000 IU/Week) administered during the week preceding the switch to the study drug.	Epoetin (1-3x/Week) n=225 Participants Participants received their ongoing weekly intravenous dose of Epoetin alfa or beta one, two or three times weekly for 52 weeks.
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Number of participants with adverse events	203 participants	202 participants	214 participants
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Number of participants with serious adverse events	101 participants	87 participants	99 participants
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs) and Death Number of deaths	19 participants	15 participants	17 participants

Adverse Events

RO0503821 (1x/2 Weeks)

Serious events: 101 serious events

Other events: 166 other events

Deaths: 0 deaths

RO0503821 (1x/4 Weeks)

Serious events: 87 serious events

Other events: 151 other events

Deaths: 0 deaths

Epoetin (1-3x/Weeks)

Serious events: 99 serious events

Other events: 175 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 616878333

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER