Trial Outcomes & Findings for A Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis. (NCT NCT00048048)

Last Updated: 2018-01-02

Results Overview

The primary efficacy variable was blood Hb level and its changes from Baseline (defined as the mean Hb of Screening assessment (SA) (Week -3), Weeks -2 and -1 of the Run-in period) over time during the core treatment period. For each participant, the primary efficacy parameter was the change in hemoglobin level over time based on regression slopes. All values until end-of-initial treatment (EOIT), defined as the last observed value before a dose change or blood transfusion, were included in the calculation of this endpoint. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

65 participants

Primary outcome timeframe

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

Results posted on

2018-01-02

Participant Flow

The study was conducted across 15 centers in 5 countries from 07 March 2002 until 23 November 2004 (last date of extension Year 2)

Participant milestones

Participant milestones
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) Eligible participants received RO0503821 (methoxy polyethylene glycol-epoetin beta \[Mircera\]) at a dose of 0.15 microgram per kilogram (mcg/kg) subcutaneously (SC) once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) Eligible participants received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/Week) Eligible participants received RO0503821 at the dose of either 0.15 mcg/kg (Cohort 1) or 0.3 mcg/kg (Cohort 2) or 0.6 mcg/kg (Cohort 3) SC once weekly over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/2Week) Eligible participants received RO0503821 at the dose of either 0.3 mcg/kg (Cohort 4) or 0.6 mcg/kg (Cohort 5) or 1.2 mcg/kg (Cohort 6) SC once every two weeks over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/3week) Eligible participants received RO0503821 at the dose of either 0.45 mcg/kg (Cohort 7) or 0.9 mcg/kg (Cohort 8) or 1.8 mcg/kg (Cohort 9) SC once every three weeks over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Core Treatment STARTED	6	6	10	6	6	9	6	6	10	0	0	0
Core Treatment COMPLETED	6	6	9	6	6	9	6	5	10	0	0	0
Core Treatment NOT COMPLETED	0	0	1	0	0	0	0	1	0	0	0	0
Extension Year 1 STARTED	0	0	0	0	0	0	0	0	0	16	16	19
Extension Year 1 COMPLETED	0	0	0	0	0	0	0	0	0	14	14	15
Extension Year 1 NOT COMPLETED	0	0	0	0	0	0	0	0	0	2	2	4
Extension Year 2 STARTED	0	0	0	0	0	0	0	0	0	2	23	15
Extension Year 2 COMPLETED	0	0	0	0	0	0	0	0	0	2	19	13
Extension Year 2 NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	4	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/Week) Eligible participants received RO0503821 at the dose of either 0.15 mcg/kg (Cohort 1) or 0.3 mcg/kg (Cohort 2) or 0.6 mcg/kg (Cohort 3) SC once weekly over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/2Week) Eligible participants received RO0503821 at the dose of either 0.3 mcg/kg (Cohort 4) or 0.6 mcg/kg (Cohort 5) or 1.2 mcg/kg (Cohort 6) SC once every two weeks over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	RO0503821 (1x/3week) Eligible participants received RO0503821 at the dose of either 0.45 mcg/kg (Cohort 7) or 0.9 mcg/kg (Cohort 8) or 1.8 mcg/kg (Cohort 9) SC once every three weeks over a period of 18 weeks. Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Core Treatment Withdrawal by Subject	1	0	0	0	0
Core Treatment Adverse Event	0	1	0	0	0
Extension Year 1 Early withdrawals	0	0	2	2	4
Extension Year 2 Early withdrawals	0	0	0	4	2

Baseline Characteristics

A Study of Mircera in Anemic Patients With Chronic Kidney Disease Not Yet on Dialysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821,0.3 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821,0.6 mcg/kg 1x/Week) n=10 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) n=9 Participants Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821,1.8 mcg/kg 1x/3 Week) n=10 Participants Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Total n=65 Participants Total of all reporting groups
Age, Continuous	58.2 Years STANDARD_DEVIATION 21.66 • n=5 Participants	70.0 Years STANDARD_DEVIATION 13.75 • n=7 Participants	58.0 Years STANDARD_DEVIATION 16.55 • n=5 Participants	60.3 Years STANDARD_DEVIATION 16.80 • n=4 Participants	62.7 Years STANDARD_DEVIATION 21.29 • n=21 Participants	62.3 Years STANDARD_DEVIATION 12.63 • n=10 Participants	66.5 Years STANDARD_DEVIATION 9.42 • n=115 Participants	54.5 Years STANDARD_DEVIATION 16.85 • n=6 Participants	58.3 Years STANDARD_DEVIATION 18.42 • n=6 Participants	60.9 Years STANDARD_DEVIATION 16.20 • n=64 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=10 Participants	4 Participants n=115 Participants	5 Participants n=6 Participants	4 Participants n=6 Participants	42 Participants n=64 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	2 Participants n=115 Participants	1 Participants n=6 Participants	6 Participants n=6 Participants	23 Participants n=64 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. Maximum number of participants with available data was reported.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=10 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) n=9 Participants Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) n=10 Participants Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
The Change in Hemoglobin Over Time Between Baseline and End of Initial Treatment Based on Individual Regression Slopes	0.48 gram/deciliter (g/dL) Interval -0.23 to 1.23	1.08 gram/deciliter (g/dL) Interval 0.98 to 1.32	1.34 gram/deciliter (g/dL) Interval 0.47 to 2.12	0.17 gram/deciliter (g/dL) Interval -0.47 to 0.52	0.27 gram/deciliter (g/dL) Interval -0.47 to 1.11	2.17 gram/deciliter (g/dL) Interval 1.38 to 2.61	0.41 gram/deciliter (g/dL) Interval 0.27 to 0.73	0.83 gram/deciliter (g/dL) Interval 0.03 to 1.75	1.28 gram/deciliter (g/dL) Interval 0.86 to 1.67

SECONDARY outcome

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

Population: The ITT population was defined as all randomized participants. Maximum number of participants with available data was reported.

Hematocrit (Hct) levels at end of initial treatment under constant dosing regimen were reported. Baseline (Day -28 to Day 1) Hct values was calculated as the mean of the SA (Week -3) 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, the EOIT value was identical to the value for Week 19.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=10 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) n=9 Participants Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) n=10 Participants Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Hematocrit Levels at End of Initial Treatment Under Constant Dosing Regimen	31.10 g/dL Interval 30.0 to 33.1	39.10 g/dL Interval 32.7 to 39.9	36.95 g/dL Interval 32.3 to 42.0	28.40 g/dL Interval 28.0 to 31.9	34.70 g/dL Interval 32.0 to 37.7	40.50 g/dL Interval 34.4 to 42.2	32.70 g/dL Interval 27.7 to 32.9	37.75 g/dL Interval 26.6 to 39.0	39 g/dL Interval 33.9 to 42.3

SECONDARY outcome

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

Population: The ITT population was defined as all randomized participants. Maximum number of participants with available data was reported.

Reticulocyte levels at EOIT under constant dosing regimen was analysed and reported. Baseline (Day -28 to Day 1) reticulocyte values were calculated as the mean of the SA (Week -3) and Run-in period (Weeks -2 and -1). For all participants, an EOIT value was calculated as the last observed reticulocyte count before a dose change or blood transfusion. For participants without any dose adjustments, the EOIT value was identical to the value for Week 19.

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) n=3 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=10 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) n=5 Participants Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) n=9 Participants Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) n=5 Participants Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) n=10 Participants Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Reticulocyte Count at End of Initial Treatment Under Constant Dosing Regimen	71.80 Cells x10^3/UL Interval 45.0 to 89.7	46.30 Cells x10^3/UL Interval 42.0 to 50.0	44.70 Cells x10^3/UL Interval 36.56 to 72.5	51.80 Cells x10^3/UL Interval 48.3 to 54.2	72.80 Cells x10^3/UL Interval 39.0 to 90.0	59.20 Cells x10^3/UL Interval 40.9 to 63.5	25.20 Cells x10^3/UL Interval 20.0 to 43.0	38.45 Cells x10^3/UL Interval 28.6 to 50.9	56.20 Cells x10^3/UL Interval 39.7 to 70.0

SECONDARY outcome

Timeframe: Up to Week 125

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, 0.15 mcg/kg 1x/Week) n=22 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=21 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=22 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Number of Participants With Any Serious Adverse Events and Any Adverse Events Participants with SAEs	11 participants	9 participants	12 participants	—	—	—	—	—	—
Number of Participants With Any Serious Adverse Events and Any Adverse Events Participants with AEs	22 participants	21 participants	22 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 125

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 (according to the Roche specified limits) which was considered to be potentially clinically relevant. The Roche reference range are: white blood cells (WBC) (3.0-18.0 10\^9 cells/L), platelets (100-550 10\^9 cells/L), alanine aminotransferase (ALT) \[0-110 units per litre (U/L)\], alkaline phosphatase (ALP) (0-220 U/L), aspartate aminotransferase (AST) (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), total bilirubin (0-17 µmol/L), lymphocytes (1- 4.80 10\^9 cells/L), eosinophils (0 - 0.45 10\^9 cells/L), monocytes (0 - 0.8 10\^9 cells/L), and neutrophils (1.80 - 7.70 10\^9 cells/L). 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, 0.15 mcg/kg 1x/Week) n=22 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=21 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=22 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Platelets - High, n = 16, 15, 19	0 participants	1 participants	0 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Platelets - Low, n = 16, 15, 19	0 participants	0 participants	3 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time WBC - High, n = 16, 15, 19	0 participants	0 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Eosinophils - High, n = 15, 15, 19	0 participants	1 participants	2 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Lymphocytes - Low, n = 15, 15, 19	2 participants	2 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Monocytes - High, n = 15, 15, 19	0 participants	0 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Neutrophils - High, n = 15, 15, 19	0 participants	3 participants	3 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Neutrophils - Low, n = 15, 15, 19	0 participants	2 participants	0 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time ALT - High, n = 22, 21, 22	1 participants	1 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time ALP - High, n = 22, 21, 22	1 participants	0 participants	2 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time AST - High, n = 22, 21, 22	2 participants	1 participants	2 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Total bilirubin - High, n = 22, 21, 22	0 participants	0 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Albumin - Low, n = 22, 21, 22	2 participants	0 participants	2 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Phosphate - High , n = 12, 13, 14	7 participants	6 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Phosphate - Low, n = 12, 13, 14	2 participants	1 participants	1 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Potassium - High, n = 22, 21, 22	3 participants	2 participants	2 participants	—	—	—	—	—	—
Number of Participants With Marked Laboratory Abnormalities for Blood Chemistry and Electrolytes Over Time Potassium - Low, n = 22, 21, 22	1 participants	0 participants	0 participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 125

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

Heart rate was defined as the measure of heart beats per minute (bpm). 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, 0.15 mcg/kg 1x/Week) n=22 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=21 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=22 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Heart Rate Over Time	65.6 bpm Standard Deviation 4.3	68.4 bpm Standard Deviation 9.8	75.4 bpm Standard Deviation 10.4	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline (Day -28 to Day 1) to Week 125

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

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 SA (Week -3) and Run-in period (Week -2 and Week -1).

Outcome measures

Outcome measures
Measure	Cohort 1 (RO0503821, 0.15 mcg/kg 1x/Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.15 mcg/kg SC once every week to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 2 (RO0503821, 0.3 mcg/kg 1x/Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.3 mcg/kg SC once every week to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 3 (RO0503821, 0.6 mcg/kg 1x/Week) n=10 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 4 (RO0503821, 0.3 mcg/kg 1x/2 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.3 mcg/kg SC once every two week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 5 (RO0503821, 0.6 mcg/kg 1x/2Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.6 mcg/kg SC once every two week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 6 (RO0503821, 1.2 mcg/kg 1x/2 Week) n=9 Participants Eligible participants received RO0503821 at a dose of 1.2 mcg/kg SC once every two week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 7 (RO0503821, 0.45 mcg/kg 1x/3 Week) n=6 Participants Eligible participants in received RO0503821 at a dose of 0.45 mcg/kg SC once every three week, to complete the dosage of 0.9 mcg/kg up to 6 weeks (Week 1 to Week 6). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 8 (RO0503821, 0.9 mcg/kg 1x/3Week) n=6 Participants Eligible participants received RO0503821 at a dose of 0.9 mcg/kg SC once every three week, to complete the dosage of 1.8 mcg/kg up to 6 weeks (Week 7 to Week 12). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.	Cohort 9 (RO0503821, 1.8 mcg/kg 1x/3 Week) n=10 Participants Eligible participants received RO0503821 at a dose of 1.8 mcg/kg SC once every three week, to complete the dosage of 3.6 mcg/kg up to 6 weeks (Week 13 to Week 18). Participants were followed-up for one week post the treatment period. During extension Years 1 and 2, the participants remained at the same frequency of administration as that of core treatment period.
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure DBP	2 mmHg Standard Deviation 10.5	5 mmHg Standard Deviation 6.6	6 mmHg Standard Deviation 5.9	6 mmHg Standard Deviation 13.7	2 mmHg Standard Deviation 9.4	-3 mmHg Standard Deviation 8.3	6 mmHg Standard Deviation 10.3	-2 mmHg Standard Deviation 12.9	4 mmHg Standard Deviation 10.3
Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure SBP	12 mmHg Standard Deviation 20.2	2 mmHg Standard Deviation 15.9	5 mmHg Standard Deviation 16.7	2 mmHg Standard Deviation 16.7	8 mmHg Standard Deviation 3.8	-11 mmHg Standard Deviation 16.3	6 mmHg Standard Deviation 16.5	3 mmHg Standard Deviation 10.0	-3 mmHg Standard Deviation 25.5

Adverse Events

RO0503821 (1x/Week)

Serious events: 11 serious events

Other events: 16 other events

Deaths: 0 deaths

RO0503821 (1x/2Week)

Serious events: 9 serious events

Other events: 18 other events

Deaths: 0 deaths

RO0503821 (1x/3week)

Serious events: 12 serious events

Other events: 22 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