Trial Outcomes & Findings for A Study of Intravenous (iv) Mircera in Hemodialysis Patients With Chronic Renal Anemia (NCT NCT00048035)

Last Updated: 2016-12-20

Results Overview

Median change from Baseline in hemoglobin (Hb) levels to end of initial treatment (EOIT) under constant dosing regimen was reported. For ease of interpretation, all individual slope values were multiplied by 42 to give an estimate of change in Hb values over six weeks. Baseline (Day -28 to Day 1) Hb values was calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1). For all participants, an EOIT value was calculated as the last observed Hb value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 value.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

91 participants

Primary outcome timeframe

From Baseline (Day -28 to Day 1) to EOIT (Week 19)

Results posted on

2016-12-20

Participant Flow

A total of 91 participants were enrolled in this study conducted from 19 March 2002 to 08 June 2005 at 14 Sites in United States.

Participant milestones

Participant milestones
Measure	Cohort 1 (RO0503821 [0.25/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2 Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2 Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/Week) Eligible participants were administered intravenously (IV) RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) once weekly (1x/ week) using a dose conversion factor of 0.25/150-, 0.40/150-, and 0.60/150 microgram (mcg)/kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose in Cohort 1, Cohort 3, and Cohort 5, respectively for 19 weeks. The ESA dose 62.5%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.25/150, 0.40/150 and 0.60/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/2Week) Eligible participants were administered IV RO0503821 once every two weeks (1x/ 2week) using a dose conversion factor of 0.25/150, 0.40/150, and 0.60/150 mcg/kg of the previous weekly ESA dose in Cohort 2, Cohort 4, and Cohort 6, respectively for 19 weeks. The ESA dose 62.5%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.25/150, 0.40/150 and 0.60/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Core Period STARTED	15	15	15	15	16	15	0	0
Core Period COMPLETED	11	13	14	14	15	14	0	0
Core Period NOT COMPLETED	4	2	1	1	1	1	0	0
Extension Year 1 STARTED	0	0	0	0	0	0	27	26
Extension Year 1 COMPLETED	0	0	0	0	0	0	16	15
Extension Year 1 NOT COMPLETED	0	0	0	0	0	0	11	11
Extension Year 2 STARTED	0	0	0	0	0	0	14	13
Extension Year 2 COMPLETED	0	0	0	0	0	0	11	10
Extension Year 2 NOT COMPLETED	0	0	0	0	0	0	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1 (RO0503821 [0.25/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2 Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/ Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2 Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/Week) Eligible participants were administered intravenously (IV) RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) once weekly (1x/ week) using a dose conversion factor of 0.25/150-, 0.40/150-, and 0.60/150 microgram (mcg)/kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose in Cohort 1, Cohort 3, and Cohort 5, respectively for 19 weeks. The ESA dose 62.5%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.25/150, 0.40/150 and 0.60/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/2Week) Eligible participants were administered IV RO0503821 once every two weeks (1x/ 2week) using a dose conversion factor of 0.25/150, 0.40/150, and 0.60/150 mcg/kg of the previous weekly ESA dose in Cohort 2, Cohort 4, and Cohort 6, respectively for 19 weeks. The ESA dose 62.5%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.25/150, 0.40/150 and 0.60/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Core Period Early Withdrawals	4	2	1	1	1	1	0	0
Extension Year 1 Early Withdrawals	0	0	0	0	0	0	11	11
Extension Year 2 Early Withdrawals	0	0	0	0	0	0	3	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2 Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2 Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Total n=91 Participants Total of all reporting groups
Age, Continuous	50.2 years STANDARD_DEVIATION 9.90 • n=5 Participants	58.6 years STANDARD_DEVIATION 12.64 • n=7 Participants	53.8 years STANDARD_DEVIATION 12.72 • n=5 Participants	62.8 years STANDARD_DEVIATION 15.76 • n=4 Participants	60.1 years STANDARD_DEVIATION 11.89 • n=21 Participants	62.5 years STANDARD_DEVIATION 10.77 • n=10 Participants	58.00 years STANDARD_DEVIATION 12.91 • n=115 Participants
Gender Female	2 Participants n=5 Participants	8 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	6 Participants n=21 Participants	3 Participants n=10 Participants	31 Participants n=115 Participants
Gender Male	13 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	9 Participants n=4 Participants	10 Participants n=21 Participants	12 Participants n=10 Participants	60 Participants n=115 Participants

PRIMARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to EOIT (Week 19)

Population: The Intent-to-Treat (ITT) population was defined as all randomized participants.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Median Change From Baseline in Hemoglobin Levels to End of Initial Treatment Under Constant Dosing Regimen	-0.29 g/dL Interval -1.14 to 0.08	-0.92 g/dL Interval -1.72 to 0.29	-0.04 g/dL Interval -0.41 to 1.24	-0.46 g/dL Interval -1.26 to -0.05	0.86 g/dL Interval 0.15 to 1.31	-0.07 g/dL Interval -0.93 to 0.48

SECONDARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to EOIT (Week 19)

Population: The Intent-to-Treat (ITT) population was defined as all randomized participants.

Median change from Baseline in hematocrit (Hct) levels to end of initial treatment under constant dosing regimen was reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA and run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed Hct value before a dose change or blood transfusion. For participants without any dose adjustments or blood transfusion, the EOIT value was identical to the Week 19 value.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Median Change From Baseline in Hematocrit Levels to End of Initial Treatment Under Constant Dosing Regimen	-1.50 g/dL Interval -3.31 to 0.3	-3.01 g/dL Interval -5.14 to -0.89	-0.32 g/dL Interval -1.26 to 4.08	-1.62 g/dL Interval -4.25 to -0.21	2.73 g/dL Interval 0.37 to 4.28	-0.07 g/dL Interval -2.57 to 1.51

SECONDARY outcome

Timeframe: Up to Week 126

Population: The safety population was considered for analysis which included all participants who received at least one dose of study drug.

An Adverse Events (AEs) 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. Serious Adverse Events (SAEs) 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. ). The study design tested 3 different starting dose conversion factors at 3 different dosing schedules during the core study period. As study drug doses can be modified continually over time all results for the two long term safety periods were displayed by dose schedule group only.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=46 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=45 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths Any AEs	42 Participants	37 Participants	—	—	—	—
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths Any SAEs	20 Participants	20 Participants	—	—	—	—
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths Deaths	3 Participants	2 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 126

Population: The safety population was considered for analysis which included all participants who received at least one dose of study drug.

Marked abnormality was defined as above and/or below a value which was considered to be potentially clinically relevant. The number of participants with marked lab abnormality across treatment groups were reported and presented. Marked laboratory abnormalities were analyzed according to the Roche specified limits for the following reference range: White blood cells (WBC) (3.0- 18.0 10\^9/L), Platelets (100 - 550 10\^9/L), Alanine aminotransferase (ALAT) \[0 110 units per litre (U/L)\], Alkaline Phosphatase (ALP) (0 - 220 U/L), Aspartate aminotransferase (ASAT) (0 - 80 U/L), Albumin \>= 30 g/L, Phosphate \[0.75 - 1.60 millimoles per liter (mmol/L)\], Potassium (2.9 - 5.8 mmol/L), Glucose (2.80 - 11.10 mmol/L).

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Number of Participants With Marked Laboratory Abnormalities Monocytes - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Phosphate -High; (n = 15, 15, 15, 15 , 16 , 15)	3 Participants	1 Participants	3 Participants	4 Participants	4 Participants	2 Participants
Number of Participants With Marked Laboratory Abnormalities Phosphate -Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Potassium -High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Potassium -Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Platelets - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Platelets - Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities WBC - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities WBC - Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Basophils - High; (n = 15, 15, 14, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Eosinophils - High; (n = 15, 15, 14, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Lymphocytes - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Lymphocytes - Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	3 Participants	2 Participants	1 Participants	2 Participants	3 Participants
Number of Participants With Marked Laboratory Abnormalities Monocytes - Low; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Neutrophils - Low; (n = 15, 15, 14, 15 , 16 , 15)	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities ALAT - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities ALP - High; (n = 15, 15, 15, 15 , 16 , 15)	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Marked Laboratory Abnormalities ASAT - High; (n = 15, 15, 15, 15 , 16 , 15)	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Total Bilirubin-High; (n = 15, 15, 15, 15, 16, 15)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Marked Laboratory Abnormalities Albumin - Low; (n = 15, 15, 15, 15 , 16 , 15)	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Glucose Fasting -High; (n = 5, 6, 9, 6, 6 , 9)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Glucose Fasting -Low; (n = 5, 6, 9, 6, 6 , 9)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to Week 126

Population: The safety population was considered for analysis which included all participants who received at least one dose of study drug.

Mean Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) is calculated as the end of treatment values minus the Baseline value. Baseline (Day -28 to Day 1) values were calculated as the mean of the screening assessment (SA) and run-in period (Week -2 and Week -1).

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis DBP- before dialysis	-2 mm HG Standard Deviation 12.2	-1 mm HG Standard Deviation 14.7	-10 mm HG Standard Deviation 12.4	-8 mm HG Standard Deviation 14.3	-6 mm HG Standard Deviation 13.1	-10 mm HG Standard Deviation 12.4
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis DBP - After dialysis	4 mm HG Standard Deviation 16.7	0 mm HG Standard Deviation 19.0	-0 mm HG Standard Deviation 14.5	-8 mm HG Standard Deviation 18.0	-6 mm HG Standard Deviation 18.1	-0 mm HG Standard Deviation 14.5
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis SBP - before dialysis	-1 mm HG Standard Deviation 26.4	5 mm HG Standard Deviation 25.5	-15 mm HG Standard Deviation 21.6	-15 mm HG Standard Deviation 23.8	-11 mm HG Standard Deviation 21.7	-15 mm HG Standard Deviation 21.6
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis SBP - After dialysis	6 mm HG Standard Deviation 30.1	3 mm HG Standard Deviation 26.5	-3 mm HG Standard Deviation 30.4	-13 mm HG Standard Deviation 26.7	-6 mm HG Standard Deviation 27.1	-3 mm HG Standard Deviation 30.4

SECONDARY outcome

Timeframe: Up to Week 126

Population: The safety population was considered for analysis which included all participants who received at least one dose of study drug

Participants pulse rates in beats per minute (BpM) were analyzed at sitting position using descriptive statistical methods (ie, means, standard deviations and percentiles). The changes in pulse rate throughout the study were analysed at each study visit and mean change is reported.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821 [0.25/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 2 (RO0503821 [0.25/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.25/150 mcg/kg of the previous weekly ESA dose, (equal to62.50% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 3 (RO0503821 [0.4/150 1x/Week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 4 (RO0503821 [0.4/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.40/150 mcg/kg of the previous weekly ESA dose, (equal to100% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 5 (RO0503821 [0.6/150 1x/Week]) n=16 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once weekly up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort 6 (RO0503821 [0.6/150 1x/2week]) n=15 Participants Eligible participant were administered RO0503821 IV using a dose conversion factor of 0.60/150 mcg/kg of the previous weekly ESA dose, (equal to150% assumed equi-effective dose) once in every two weeks up to 19 weeks. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Mean Change in Pulse Rate	-1 BpM Standard Deviation 10.1	1 BpM Standard Deviation 14.8	2 BpM Standard Deviation 10.5	3 BpM Standard Deviation 14.1	-1 BpM Standard Deviation 10.2	3 BpM Standard Deviation 12.6

Adverse Events

RO0503821 (1/Week)

Serious events: 20 serious events

Other events: 34 other events

Deaths: 0 deaths

RO0503821 (1/2week)

Serious events: 20 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Roche Trial Information Hotline

F. Hoffmann-La Roche AG

Phone: +41 61 6878333

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