Trial Outcomes & Findings for A Study of Subcutaneous (sc) Mircera in Dialysis Patients With Chronic Renal Anemia. (NCT NCT00364832)

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 -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 (or Week 21) value.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

From Baseline (Day -28 to Day 1) to EOIT (Week 19 or Week 21)

Results posted on

2016-12-20

Participant Flow

A total of 137 participants were enrolled in this study conducted from 15 October 2001 to 7 July 2003 (core study period) and 19 September 2002 to 7 July 2005 (extension study period) at 22 centers (8 in Italy, 6 in the US, 4 in Germany, and 4 in Spain).

Participant milestones

Participant milestones
Measure	Cohort A (0.4/150, 1x/ Week) Eligible participants were administered RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) subcutaneous (SC) using a dose conversion factor of 0.4/150 microgram (mcg)/ kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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 SC RO0503821 once weekly (1x/ week) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kilogram of the previous weekly ESA dose in Cohort A, Cohort D, and Cohort G, respectively for 19 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/ 3 Weeks) Eligible participants were administered SC RO0503821 once every three weeks (1x/ 3 weeks) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kg of the previous weekly ESA dose in Cohort B, Cohort E, and Cohort H, respectively for 19 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/ 4 Weeks) Eligible participants were administered SC RO0503821 once every four weeks (1x/ 4 weeks) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kg of the previous weekly ESA dose in Cohort C, Cohort F, and Cohort I, respectively for 21 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Core Period STARTED	16	15	15	16	16	12	16	15	16	0	0	0
Core Period COMPLETED	14	13	14	15	16	12	12	14	16	0	0	0
Core Period NOT COMPLETED	2	2	1	1	0	0	4	1	0	0	0	0
Extension Year 1 STARTED	0	0	0	0	0	0	0	0	0	18	17	27
Extension Year 1 COMPLETED	0	0	0	0	0	0	0	0	0	14	15	17
Extension Year 1 NOT COMPLETED	0	0	0	0	0	0	0	0	0	4	2	10
Extension Year 2 STARTED	0	0	0	0	0	0	0	0	0	14	14	14
Extension Year 2 COMPLETED	0	0	0	0	0	0	0	0	0	9	9	11
Extension Year 2 NOT COMPLETED	0	0	0	0	0	0	0	0	0	5	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A (0.4/150, 1x/ Week) Eligible participants were administered RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) subcutaneous (SC) using a dose conversion factor of 0.4/150 microgram (mcg)/ kilogram (kg) of the previous weekly erythropoiesis stimulating agents (ESA) dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 G (1.2/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 SC RO0503821 once weekly (1x/ week) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kilogram of the previous weekly ESA dose in Cohort A, Cohort D, and Cohort G, respectively for 19 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/ 3 Weeks) Eligible participants were administered SC RO0503821 once every three weeks (1x/ 3 weeks) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kg of the previous weekly ESA dose in Cohort B, Cohort E, and Cohort H, respectively for 19 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 19 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	RO0503821 (1x/ 4 Weeks) Eligible participants were administered SC RO0503821 once every four weeks (1x/ 4 weeks) using a dose conversion factor of 0.4/150-, 0.8/150-, and 1.2/150 mcg/kg of the previous weekly ESA dose in Cohort C, Cohort F, and Cohort I, respectively for 21 weeks. The ESA dose 50%, 100%, and 150% assumed equi-effective dose for dose conversion factors 0.4/150, 0.8/150 and 1.2/150, respectively. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Core Period Early Withdrawals	2	2	1	1	4	1	0	0	0
Extension Year 1 Early Withdrawals	0	0	0	0	0	0	4	2	10
Extension Year 2 Early Withdrawals	0	0	0	0	0	0	5	5	3

Baseline Characteristics

A Study of Subcutaneous (sc) Mircera in Dialysis Patients With Chronic Renal Anemia.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Total n=137 Participants Total of all reporting groups
Age, Continuous	67.0 years STANDARD_DEVIATION 13.03 • n=5 Participants	65.6 years STANDARD_DEVIATION 11.29 • n=7 Participants	64.8 years STANDARD_DEVIATION 10.28 • n=5 Participants	61.8 years STANDARD_DEVIATION 13.51 • n=4 Participants	64.1 years STANDARD_DEVIATION 12.83 • n=21 Participants	67.3 years STANDARD_DEVIATION 13.30 • n=10 Participants	62.7 years STANDARD_DEVIATION 13.74 • n=115 Participants	58.9 years STANDARD_DEVIATION 13.12 • n=6 Participants	64.1 years STANDARD_DEVIATION 13.34 • n=6 Participants	63.9 years STANDARD_DEVIATION 12.63 • n=64 Participants
Gender Female	5 Participants n=5 Participants	8 Participants n=7 Participants	5 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	7 Participants n=10 Participants	4 Participants n=115 Participants	5 Participants n=6 Participants	7 Participants n=6 Participants	52 Participants n=64 Participants
Gender Male	11 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	10 Participants n=4 Participants	11 Participants n=21 Participants	5 Participants n=10 Participants	12 Participants n=115 Participants	10 Participants n=6 Participants	9 Participants n=6 Participants	85 Participants n=64 Participants

PRIMARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to EOIT (Week 19 or Week 21)

Population: The ITT population was considered for analysis which included all randomized participants.

Outcome measures

Outcome measures
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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	-0.80 gram per deciliter Interval -1.6 to -0.36	-0.60 gram per deciliter Interval -1.01 to -0.16	-0.29 gram per deciliter Interval -0.91 to -0.23	0.02 gram per deciliter Interval -0.4 to 0.52	-0.14 gram per deciliter Interval -0.6 to 0.27	-0.28 gram per deciliter Interval -0.77 to 0.11	0.65 gram per deciliter Interval 0.12 to 1.57	0.33 gram per deciliter Interval -0.11 to 1.14	0.22 gram per deciliter Interval -0.09 to 1.02

SECONDARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to EOIT (Week 19 or Week 21)

Population: The ITT population was considered for analysis which included 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 (or Week 21) value.

Outcome measures

Outcome measures
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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	-2.45 Percentage of Hct Interval -6.33 to -0.83	-1.95 Percentage of Hct Interval -3.28 to -0.34	-0.93 Percentage of Hct Interval -2.56 to -0.63	0.25 Percentage of Hct Interval -1.25 to 1.36	-0.37 Percentage of Hct Interval -1.67 to 1.02	-0.75 Percentage of Hct Interval -2.23 to 0.35	2.25 Percentage of Hct Interval 0.72 to 4.08	1.22 Percentage of Hct Interval -0.18 to 3.09	0.73 Percentage of Hct Interval -0.34 to 2.86

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) value is the measurements taken at screening assessment and run-in period (Weeks -2 and -1).

Outcome measures

Outcome measures
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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 SBP before dialysis	-1 Millimeters of Mercury Standard Deviation 25.5	7 Millimeters of Mercury Standard Deviation 15.5	2 Millimeters of Mercury Standard Deviation 30.4	-8 Millimeters of Mercury Standard Deviation 18.1	-4 Millimeters of Mercury Standard Deviation 10.8	-6 Millimeters of Mercury Standard Deviation 20.3	-2 Millimeters of Mercury Standard Deviation 21.4	1 Millimeters of Mercury Standard Deviation 18.6	-7 Millimeters of Mercury Standard Deviation 20
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis SBP after dialysis	0 Millimeters of Mercury Standard Deviation 24.4	10 Millimeters of Mercury Standard Deviation 34.3	1 Millimeters of Mercury Standard Deviation 26.9	-4 Millimeters of Mercury Standard Deviation 25.2	7 Millimeters of Mercury Standard Deviation 17.1	-5 Millimeters of Mercury Standard Deviation 27.6	0 Millimeters of Mercury Standard Deviation 25	-1 Millimeters of Mercury Standard Deviation 27.1	-7 Millimeters of Mercury Standard Deviation 18.2
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis DBP before dialysis	-1 Millimeters of Mercury Standard Deviation 14.2	1 Millimeters of Mercury Standard Deviation 9	3 Millimeters of Mercury Standard Deviation 12.5	-3 Millimeters of Mercury Standard Deviation 11.4	-2 Millimeters of Mercury Standard Deviation 9.4	2 Millimeters of Mercury Standard Deviation 12.9	-3 Millimeters of Mercury Standard Deviation 11.9	-0 Millimeters of Mercury Standard Deviation 11.4	1 Millimeters of Mercury Standard Deviation 8.6
Mean Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Before and After Dialysis DBP after dialysis	-3 Millimeters of Mercury Standard Deviation 14.6	4 Millimeters of Mercury Standard Deviation 10.4	-1 Millimeters of Mercury Standard Deviation 12.9	-3 Millimeters of Mercury Standard Deviation 15.8	0 Millimeters of Mercury Standard Deviation 11.1	2 Millimeters of Mercury Standard Deviation 13.4	-3 Millimeters of Mercury Standard Deviation 12.2	5 Millimeters of Mercury Standard Deviation 10.2	-5 Millimeters of Mercury Standard Deviation 10.3

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 with available data at the time of evaluation were analyzed.

Mean change in pulse rate was reported.

Outcome measures

Outcome measures
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).
Mean Change in Pulse Rate	-6 Beats per minute Standard Deviation 8.8	-2 Beats per minute Standard Deviation 9.1	7 Beats per minute Standard Deviation 9.1	-1 Beats per minute Standard Deviation 13.7	-1 Beats per minute Standard Deviation 7.7	2 Beats per minute Standard Deviation 8.1	2 Beats per minute Standard Deviation 9.9	0 Beats per minute Standard Deviation 6.3	1 Beats per minute Standard Deviation 9.1

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 with marked laboratory abnormalities were reported. Marked abnormality criteria: Serum glutamic oxaloacetic transaminase (SGOT); high \>25 units per litre (U/L), albumin (low \< 31 grams per litre \[g/L\]), total protein (\< 60 g/L), phosphate (high \>1.45 millimoles per litre \[mmol/L\]); Low \<0.84 mmol/L), potassium (high \>5 mmol/L; Low \<3.5 mmol/L), platelets (low:\<150×10\^9/L), White blood cells (\[WBCs\]); high: 10.8×10\^9/L and Low:4.3×10\^9/L), basophils (high:\>0.15×10\^9/L), eosinophils (high:\>0.70×10\^9/L), lymphocytes (low:\<1.50×10\^9/L), and neutrophils (low:\<1.83×10\^9/L).

Outcome measures

Outcome measures
Measure	Cohort A (0.4/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) n=12 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) n=15 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) n=16 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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 Total protein, Low	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities SGOT, High	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Marked Laboratory Abnormalities Albumin, Low	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 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.

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 A (0.4/150, 1x/ Week) n=48 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 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 B (0.4/150, 1x/ 3 Weeks) n=46 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every three 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 C (0.4/150, 1x/ 4 Weeks) n=43 Participants Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.4/150 mcg/kg of the previous weekly ESA dose, (equal to 50% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort D (0.8/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% 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 E (0.8/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every three 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 F (0.8/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 0.8/150 mcg/kg of the previous weekly ESA dose, (equal to 100% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 weeks of core treatment period, participants were followed-up for two optional treatment extension periods (54 weeks each).	Cohort G (1.2/150, 1x/ Week) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% 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 H (1.2/150, 1x/ 3 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every three 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 I (1.2/150, 1x/ 4 Weeks) Eligible participants were administered RO0503821 SC using a dose conversion factor of 1.2/150 mcg/kg of the previous weekly ESA dose, (equal to 150% assumed equi-effective dose) once every four weeks up to 21 weeks. After 21 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	44 Participants	33 Participants	40 Participants	—	—	—	—	—	—
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths Any SAEs	15 Participants	13 Participants	20 Participants	—	—	—	—	—	—
Number of Participants With Any Adverse Events, Any Serious Adverse Events, And Deaths Deaths	7 Participants	4 Participants	10 Participants	—	—	—	—	—	—

Adverse Events

RO0503821 (1x/ Week)

Serious events: 15 serious events

Other events: 36 other events

Deaths: 0 deaths

RO0503821 (1x/ 3 Weeks)

Serious events: 13 serious events

Other events: 30 other events

Deaths: 0 deaths

RO0503821 (1x/ 4 Weeks)

Serious events: 20 serious events

Other events: 39 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