Trial Outcomes & Findings for Efficacy and Safety of MEDI6570 in Patients With a History of Myocardial Infarction (NCT NCT04610892)

NCT ID: NCT04610892

Last Updated: 2025-02-21

Results Overview

To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 423 participants
• Primary outcome timeframe: From baseline to Day 253
• Results posted on: 2025-02-21

Participant Flow

Participant milestones

Measure	MEDI6570 50 mg Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 250 mg/400 mg Participants received MEDI6570 250 mg/400 mg every 4 weeks for 32 weeks.	MEDI6570 400 mg Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks
Overall Study STARTED	40	129	8	118	128
Overall Study COMPLETED	35	126	8	110	117
Overall Study NOT COMPLETED	5	3	0	8	11

Reasons for withdrawal

Measure	MEDI6570 50 mg Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 250 mg/400 mg Participants received MEDI6570 250 mg/400 mg every 4 weeks for 32 weeks.	MEDI6570 400 mg Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks
Overall Study Adverse Event	1	0	0	1	3
Overall Study Death	0	1	0	1	0
Overall Study Withdrawal by Subject	3	2	0	6	6
Overall Study Subjects who did not receive treatment	1	0	0	0	2

Baseline Characteristics

Efficacy and Safety of MEDI6570 in Patients With a History of Myocardial Infarction

Baseline characteristics by cohort

Measure	MEDI6570 50 mg n=40 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	Placebo n=128 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total n=423 Participants Total of all reporting groups
Age, Continuous	60.1 Years STANDARD_DEVIATION 8.3 • n=5 Participants	59.9 Years STANDARD_DEVIATION 9.2 • n=7 Participants	59.4 Years STANDARD_DEVIATION 9.6 • n=5 Participants	60.4 Years STANDARD_DEVIATION 9.5 • n=4 Participants	59.9 Years STANDARD_DEVIATION 9.3 • n=21 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	19 Participants n=7 Participants	23 Participants n=5 Participants	21 Participants n=4 Participants	75 Participants n=21 Participants
Sex: Female, Male Male	28 Participants n=5 Participants	110 Participants n=7 Participants	103 Participants n=5 Participants	107 Participants n=4 Participants	348 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants	19 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	124 Participants n=7 Participants	124 Participants n=5 Participants	121 Participants n=4 Participants	404 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized ASIAN	7 Participants n=5 Participants	10 Participants n=7 Participants	8 Participants n=5 Participants	9 Participants n=4 Participants	34 Participants n=21 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized OTHER	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized WHITE	33 Participants n=5 Participants	116 Participants n=7 Participants	118 Participants n=5 Participants	118 Participants n=4 Participants	385 Participants n=21 Participants
Race/Ethnicity, Customized Caucasian	33 Participants n=5 Participants	116 Participants n=7 Participants	118 Participants n=5 Participants	118 Participants n=4 Participants	385 Participants n=21 Participants
Race/Ethnicity, Customized Non-caucasian	7 Participants n=5 Participants	13 Participants n=7 Participants	8 Participants n=5 Participants	10 Participants n=4 Participants	38 Participants n=21 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment Australia	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Region of Enrollment Canada	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	4 Participants n=21 Participants
Region of Enrollment Czech Republic	2 Participants n=5 Participants	17 Participants n=7 Participants	17 Participants n=5 Participants	18 Participants n=4 Participants	54 Participants n=21 Participants
Region of Enrollment Hungary	9 Participants n=5 Participants	11 Participants n=7 Participants	12 Participants n=5 Participants	23 Participants n=4 Participants	55 Participants n=21 Participants
Region of Enrollment Italy	0 Participants n=5 Participants	14 Participants n=7 Participants	21 Participants n=5 Participants	19 Participants n=4 Participants	54 Participants n=21 Participants
Region of Enrollment Japan	7 Participants n=5 Participants	9 Participants n=7 Participants	8 Participants n=5 Participants	8 Participants n=4 Participants	32 Participants n=21 Participants
Region of Enrollment Netherlands	1 Participants n=5 Participants	18 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	41 Participants n=21 Participants
Region of Enrollment Poland	2 Participants n=5 Participants	14 Participants n=7 Participants	14 Participants n=5 Participants	10 Participants n=4 Participants	40 Participants n=21 Participants
Region of Enrollment Spain	13 Participants n=5 Participants	20 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	69 Participants n=21 Participants
Region of Enrollment United Kingdom	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants
Region of Enrollment United States of America	6 Participants n=5 Participants	12 Participants n=7 Participants	13 Participants n=5 Participants	17 Participants n=4 Participants	48 Participants n=21 Participants

PRIMARY outcome

Timeframe: From baseline to Day 253

Population: Participants within the Intention To Treat (ITT) Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following clinical study protocol (CSP) amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on non-calcified coronary atherosclerotic plaques compared with placebo. The primary endpoint of change in NCPVMD from baseline to Day 253 was assessed based on the CTA Analysis Populations.

Outcome measures

Measure	MEDI6570 50 mg n=35 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=127 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=118 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=245 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=117 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in Non-calcified Plaque Volume in the Most Diseased Coronary Segment (NCPVMD), as Measured by Computed Tomography Angiography (CTA) Imaging	-15.3220 mm^3 Standard Error 4.9219	-4.5509 mm^3 Standard Error 3.1654	-6.3658 mm^3 Standard Error 3.2559	-5.4220 mm^3 Standard Error 2.6622	-6.9424 mm^3 Standard Error 3.2729	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To evaluate the effect of MEDI6570 on a surrogate biomarker of Heart Failure (HF) compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=35 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=125 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=123 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=248 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=118 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in N Terminal Prohormone Brain Natriuretic Peptide (NT-proBNP)	0.8226 pg/mL Geometric Coefficient of Variation 9.4	0.7787 pg/mL Geometric Coefficient of Variation 5.5	0.7368 pg/mL Geometric Coefficient of Variation 5.6	0.7575 pg/mL Geometric Coefficient of Variation 4.4	0.7370 pg/mL Geometric Coefficient of Variation 5.6	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group

To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=31 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=115 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=112 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=227 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=103 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in Left Ventricular Ejection Fraction (LVEF)	-0.91 Percentage of LVEF Standard Error 0.55	0.32 Percentage of LVEF Standard Error 0.34	0.11 Percentage of LVEF Standard Error 0.35	0.22 Percentage of LVEF Standard Error 0.28	0.53 Percentage of LVEF Standard Error 0.35	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as <50%) compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=7 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=13 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=20 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=33 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=14 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Left Ventricular Ejection Fraction (LVEF) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)	-1.08 Percentage of LVEF Standard Error 1.52	1.32 Percentage of LVEF Standard Error 1.13	2.09 Percentage of LVEF Standard Error 1.00	1.79 Percentage of LVEF Standard Error 0.82	2.41 Percentage of LVEF Standard Error 1.04	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on left ventricular systolic function compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=29 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=105 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=109 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=214 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=100 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in Global Longitudinal Strain (GLS)	-1.20 Percentage of GLS Standard Error 0.56	-0.70 Percentage of GLS Standard Error 0.35	-0.77 Percentage of GLS Standard Error 0.35	-0.74 Percentage of GLS Standard Error 0.29	0.09 Percentage of GLS Standard Error 0.35	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Subjects within the ITT population who have interpretable echocardiograms in the baseline and follow-up periods will be included in the Echocardiogram Analysis Population. Subjects will be analysed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on left ventricular systolic function among participants with reduced ejection fraction (defined as <50%) compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=6 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=12 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=20 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=32 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=15 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Global Longitudinal Strain (GLS) Change From Baseline to Day 253 Among Subjects With Reduced Ejection Fraction (< 50%)	-0.39 Percentage of GLS Standard Error 1.03	-1.16 Percentage of GLS Standard Error 0.78	0.41 Percentage of GLS Standard Error 0.64	-0.19 Percentage of GLS Standard Error 0.55	1.76 Percentage of GLS Standard Error 0.66	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Participants within the ITT Population who had interpretable b CTA scans at baseline and at Day 253 or at Day 122 were included. (Note that separate analyses were conducted for Day 253 and Day 122). Participants were analyzed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=34 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=125 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=116 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=241 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=117 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in Global Non-calcified Plaque Volume (NCPV)	-26.4453 mm^3 Standard Error 10.0524	-10.9010 mm^3 Standard Error 6.4671	-10.4850 mm^3 Standard Error 6.6607	-10.7013 mm^3 Standard Error 5.4415	-10.3083 mm^3 Standard Error 6.7052	—

SECONDARY outcome

Timeframe: From baseline to Day 253

Population: Participants within the ITT Population who had interpretable CTA scans at baseline and at Day 253. Participants were analyzed according to their randomized treatment group. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the effect of MEDI6570 on other measures of non-calcified coronary atherosclerotic plaque compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=34 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=125 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=116 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=241 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=117 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Change From Baseline to Day 253 in Low Attenuation Plaque Volume (LAPV)	-7.9167 mm3 Standard Error 3.5226	-4.8101 mm3 Standard Error 2.2690	-4.2748 mm3 Standard Error 2.3363	-4.5532 mm3 Standard Error 1.9099	-3.5733 mm3 Standard Error 2.3481	—

SECONDARY outcome

Timeframe: From baseline to Day 325/405. Day 325/405: for participants who completed the study under clinical study protocol (CSP) Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.

Population: Subjects included in the As-treated Population who have ≥ 1 immunogenicity sample will be included in the Immunogenicity Population. Subjects will be analysed according to the actual treatment they received. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the immunogenicity of MEDI6570

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=294 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=126 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total n=420 Participants Overall Total
Summary of ADA (Anti-drug Antibody) Responses During the Study ADA (anti-drug antibody) prevalence (positive at baseline or post-baseline)	2 Participants	10 Participants	3 Participants	15 Participants	1 Participants	16 Participants
Summary of ADA (Anti-drug Antibody) Responses During the Study ADA (anti-drug antibody) incidence (TEADA positive)	2 Participants	9 Participants	2 Participants	13 Participants	1 Participants	14 Participants
Summary of ADA (Anti-drug Antibody) Responses During the Study Treatment-induced ADA (anti-drug antibody) positive	2 Participants	9 Participants	2 Participants	13 Participants	1 Participants	14 Participants
Summary of ADA (Anti-drug Antibody) Responses During the Study Treatment-boosted ADA (anti-drug antibody) positive	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Summary of ADA (Anti-drug Antibody) Responses During the Study ADA (anti-drug antibody) persistently positive	2 Participants	7 Participants	1 Participants	10 Participants	1 Participants	11 Participants

SECONDARY outcome

Timeframe: From Baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.

Population: Subjects included in the As-treated Population who have ≥ 1 immunogenicity sample will be included in the Immunogenicity Population. Subjects will be analysed according to the actual treatment they received. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

To evaluate the immunogenicity of MEDI6570

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=294 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=126 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total n=420 Participants Overall Total
Anti-drug Antibody Titre Summary by Visit Baseline	—	80 Titer units Interval 80.0 to 80.0	320 Titer units Interval 320.0 to 320.0	200 Titer units Interval 80.0 to 320.0	—	200 Titer units Interval 80.0 to 320.0
Anti-drug Antibody Titre Summary by Visit Day 29	—	640 Titer units Interval 640.0 to 640.0	—	640 Titer units Interval 640.0 to 640.0	—	640 Titer units Interval 640.0 to 640.0
Anti-drug Antibody Titre Summary by Visit Day 57	—	80 Titer units Interval 80.0 to 80.0	—	80 Titer units Interval 80.0 to 80.0	—	80 Titer units Interval 80.0 to 80.0
Anti-drug Antibody Titre Summary by Visit Day 113	640 Titer units Interval 640.0 to 640.0	640 Titer units Interval 640.0 to 640.0	—	640 Titer units Interval 640.0 to 640.0	—	640 Titer units Interval 640.0 to 640.0
Anti-drug Antibody Titre Summary by Visit Day 169	320 Titer units Interval 320.0 to 320.0	1600 Titer units Interval 640.0 to 2560.0	—	640 Titer units Interval 320.0 to 2560.0	—	640.0 Titer units Interval 320.0 to 2560.0
Anti-drug Antibody Titre Summary by Visit Day 253	160 Titer units Interval 160.0 to 160.0	1360 Titer units Interval 160.0 to 2560.0	80 Titer units Interval 80.0 to 80.0	160 Titer units Interval 80.0 to 2560.0	—	160 Titer units Interval 80.0 to 2560.0
Anti-drug Antibody Titre Summary by Visit Day 325/405	120.0 Titer units Interval 80.0 to 160.0	320 Titer units Interval 80.0 to 1280.0	80 Titer units Interval 80.0 to 80.0	160 Titer units Interval 80.0 to 1280.0	NA Titer units Result is positive but not quantifiable	160 Titer units Interval 80.0 to 1280.0

SECONDARY outcome

Timeframe: From baseline to Day 325/Day 405

Population: All subjects who received ≥ 1 dose of MEDI6570 and have ≥ 1 one post dose evaluable MEDI6570 serum concentration will be included in the PK population. Subjects will be analysed according to the actual treatment they received. The pk data was analysed only for 50 mg, 150mg and 400mg groups.

MEDI6570 concentrations as measured in serum during the intervention and follow-up periods

Outcome measures

Measure	MEDI6570 50 mg n=38 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=117 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Summary of Serum Concentrations (ug/mL) of MEDI6570 Baseline	NA ug/mL Geometric Coefficient of Variation NA All subjects had values below limit of quantification (LLOQ)	NA ug/mL Geometric Coefficient of Variation NA All subjects had values below limit of quantification (LLOQ)	NA ug/mL Geometric Coefficient of Variation NA All subjects had values below limit of quantification (LLOQ)	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 10	2.3126 ug/mL Geometric Coefficient of Variation 101.5	7.0296 ug/mL Geometric Coefficient of Variation 125.9	20.4472 ug/mL Geometric Coefficient of Variation 37.2	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 29	0.6154 ug/mL Geometric Coefficient of Variation 170.7	3.4641 ug/mL Geometric Coefficient of Variation 103.2	9.5328 ug/mL Geometric Coefficient of Variation 115.4	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 57	0.7622 ug/mL Geometric Coefficient of Variation 235.5	4.3897 ug/mL Geometric Coefficient of Variation 145.9	15.0108 ug/mL Geometric Coefficient of Variation 50.3	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 85	1.1353 ug/mL Geometric Coefficient of Variation 217.3	6.4317 ug/mL Geometric Coefficient of Variation 62.0	10.8714 ug/mL Geometric Coefficient of Variation 608.2	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 113	1.0084 ug/mL Geometric Coefficient of Variation 176.7	5.4403 ug/mL Geometric Coefficient of Variation 120.1	15.5611 ug/mL Geometric Coefficient of Variation 77.1	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 122	4.6703 ug/mL Geometric Coefficient of Variation 37.0	8.1229 ug/mL Geometric Coefficient of Variation 792.0	28.1805 ug/mL Geometric Coefficient of Variation 168.8	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 141	1.4191 ug/mL Geometric Coefficient of Variation 129.5	8.0736 ug/mL Geometric Coefficient of Variation 47.2	10.4080 ug/mL Geometric Coefficient of Variation 647.5	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 169	0.8016 ug/mL Geometric Coefficient of Variation 171.6	5.2865 ug/mL Geometric Coefficient of Variation 163.4	15.9449 ug/mL Geometric Coefficient of Variation 145.9	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 197	—	—	NA ug/mL Geometric Coefficient of Variation NA Not calculable. only 1 patient attend on Day 197 in this group	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 225	2.2469 ug/mL Geometric Coefficient of Variation 86.3	3.6384 ug/mL Geometric Coefficient of Variation 633.4	—	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 253	0.7253 ug/mL Geometric Coefficient of Variation 288.4	5.6832 ug/mL Geometric Coefficient of Variation 136.0	14.9944 ug/mL Geometric Coefficient of Variation 173.4	—	—	—
Summary of Serum Concentrations (ug/mL) of MEDI6570 Day 325/Day 405	NA ug/mL Geometric Coefficient of Variation NA All subjects had values below limit of quantification (LLOQ)	NA ug/mL Geometric Coefficient of Variation NA All subjects had values below limit of quantification (LLOQ)	0.5955 ug/mL Geometric Coefficient of Variation 720.6	—	—	—

SECONDARY outcome

Timeframe: During study follow-up (from day 1 to day 325)

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To assess the safety and tolerability of MEDI6570 compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=294 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=126 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Number of Participants With Adverse Events in Any Category Any AEs	26 Participants	87 Participants	79 Participants	192 Participants	65 Participants	—
Number of Participants With Adverse Events in Any Category Any AEs with outcome of death	0 Participants	1 Participants	1 Participants	2 Participants	0 Participants	—
Number of Participants With Adverse Events in Any Category Any SAE (including events with outcome of death)	4 Participants	17 Participants	10 Participants	31 Participants	13 Participants	—
Number of Participants With Adverse Events in Any Category Any AE leading to treatment discontinuation	1 Participants	0 Participants	2 Participants	3 Participants	3 Participants	—
Number of Participants With Adverse Events in Any Category Any AE leading to withdrawal from study	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: During study follow-up (from day 1 to day 325)

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To assess the safety and tolerability of MEDI6570 compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=294 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo n=126 Participants Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Number of Participants With Most Common Adverse Events (Frequency > 5%) Participants with any AE	16 Participants	35 Participants	38 Participants	89 Participants	26 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) COVID-19	3 Participants	8 Participants	17 Participants	28 Participants	6 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Hypertension	2 Participants	4 Participants	9 Participants	15 Participants	9 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Non-cardiac chest pain	3 Participants	5 Participants	6 Participants	14 Participants	4 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Dyspnoea	2 Participants	3 Participants	4 Participants	9 Participants	3 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Hypotension	2 Participants	1 Participants	4 Participants	7 Participants	1 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Angina pectoris	2 Participants	10 Participants	3 Participants	15 Participants	6 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Pyrexia	2 Participants	1 Participants	3 Participants	6 Participants	1 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Diarrhoea	2 Participants	5 Participants	2 Participants	9 Participants	4 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Epistaxis	2 Participants	1 Participants	2 Participants	5 Participants	1 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Influenza	2 Participants	4 Participants	2 Participants	8 Participants	1 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Nausea	2 Participants	1 Participants	1 Participants	4 Participants	1 Participants	—
Number of Participants With Most Common Adverse Events (Frequency > 5%) Pain in extremity	2 Participants	1 Participants	1 Participants	4 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To assess the safety and tolerability of MEDI6570 compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=126 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 10	0.3 mmHg Standard Deviation 9.9	0.9 mmHg Standard Deviation 12.7	-1.4 mmHg Standard Deviation 13.0	0.4 mmHg Standard Deviation 12.8	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 29	-0.7 mmHg Standard Deviation 10.8	-1.1 mmHg Standard Deviation 14.6	-1.5 mmHg Standard Deviation 11.9	-1.3 mmHg Standard Deviation 12.6	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 57	1.4 mmHg Standard Deviation 11.6	0.7 mmHg Standard Deviation 14.1	-1.6 mmHg Standard Deviation 12.3	-0.1 mmHg Standard Deviation 12.8	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 85	0.7 mmHg Standard Deviation 10.2	1.5 mmHg Standard Deviation 13.8	-1.2 mmHg Standard Deviation 12.7	-0.5 mmHg Standard Deviation 14.9	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 113	-0.6 mmHg Standard Deviation 10.6	1.3 mmHg Standard Deviation 15.2	0.2 mmHg Standard Deviation 13.7	0.6 mmHg Standard Deviation 13.1	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 122	1.6 mmHg Standard Deviation 16.4	-4.0 mmHg Standard Deviation 15.5	-2.0 mmHg Standard Deviation 13.8	7.8 mmHg Standard Deviation 17.1	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 141	0.7 mmHg Standard Deviation 15.0	-0.2 mmHg Standard Deviation 14.1	-0.2 mmHg Standard Deviation 14.1	0.8 mmHg Standard Deviation 13.3	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 169	1.2 mmHg Standard Deviation 13.4	1.5 mmHg Standard Deviation 12.5	-0.3 mmHg Standard Deviation 14.9	0.5 mmHg Standard Deviation 14.5	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 197	0.7 mmHg Standard Deviation 15.8	0.6 mmHg Standard Deviation 14.0	-3.6 mmHg Standard Deviation 13.5	-0.4 mmHg Standard Deviation 13.6	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 225	2.8 mmHg Standard Deviation 14.3	1.7 mmHg Standard Deviation 14.8	-0.6 mmHg Standard Deviation 15.1	-0.3 mmHg Standard Deviation 14.7	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 253	-1.8 mmHg Standard Deviation 15.5	0.7 mmHg Standard Deviation 14.4	-0.9 mmHg Standard Deviation 15.6	0.2 mmHg Standard Deviation 14.5	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Systolic blood pressure Day 325/405	-1.8 mmHg Standard Deviation 12.8	0.7 mmHg Standard Deviation 14.1	-2.5 mmHg Standard Deviation 14.7	0.1 mmHg Standard Deviation 16.0	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 10	-0.2 mmHg Standard Deviation 6.0	0.6 mmHg Standard Deviation 8.5	-0.3 mmHg Standard Deviation 8.4	-0.4 mmHg Standard Deviation 8.7	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 29	0.3 mmHg Standard Deviation 8.5	-1.3 mmHg Standard Deviation 8.7	-1.1 mmHg Standard Deviation 9.7	-1.3 mmHg Standard Deviation 9.1	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 57	-1.1 mmHg Standard Deviation 8.5	-0.5 mmHg Standard Deviation 8.4	-0.9 mmHg Standard Deviation 8.9	-0.4 mmHg Standard Deviation 8.5	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 85	-0.1 mmHg Standard Deviation 9.0	-0.5 mmHg Standard Deviation 10.5	-0.9 mmHg Standard Deviation 8.9	-0.6 mmHg Standard Deviation 9.2	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 113	-0.3 mmHg Standard Deviation 8.5	0.1 mmHg Standard Deviation 9.4	-0.5 mmHg Standard Deviation 8.9	1.0 mmHg Standard Deviation 9.1	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 122	-3.7 mmHg Standard Deviation 10.4	-3.9 mmHg Standard Deviation 8.0	-2.0 mmHg Standard Deviation 7.5	4.1 mmHg Standard Deviation 12.3	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 141	-1.5 mmHg Standard Deviation 8.4	-1.1 mmHg Standard Deviation 9.6	-0.3 mmHg Standard Deviation 8.5	0.2 mmHg Standard Deviation 7.9	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 169	-0.4 mmHg Standard Deviation 9.5	-0.3 mmHg Standard Deviation 9.2	-0.8 mmHg Standard Deviation 9.0	-0.4 mmHg Standard Deviation 9.2	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 197	-1.6 mmHg Standard Deviation 7.7	0.0 mmHg Standard Deviation 9.5	-2.0 mmHg Standard Deviation 9.8	-0.3 mmHg Standard Deviation 9.0	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 225	0.4 mmHg Standard Deviation 9.5	-1.6 mmHg Standard Deviation 9.8	-0.9 mmHg Standard Deviation 8.8	-0.8 mmHg Standard Deviation 8.4	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 253	-3.7 mmHg Standard Deviation 7.9	-0.1 mmHg Standard Deviation 10.7	-1.0 mmHg Standard Deviation 9.9	-0.4 mmHg Standard Deviation 9.3	—	—
Vital Signs (Change in Systolic and Diastolic Blood Pressure From Baseline) Over Time Diastolic blood pressure Day 325/405	-1.8 mmHg Standard Deviation 8.5	-0.5 mmHg Standard Deviation 9.1	-1.5 mmHg Standard Deviation 10.3	-0.7 mmHg Standard Deviation 9.8	—	—

SECONDARY outcome

Timeframe: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively.

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To assess the safety and tolerability of MEDI6570 compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=126 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 10	0.4 beats/min Standard Deviation 9.4	0.6 beats/min Standard Deviation 8.0	0.4 beats/min Standard Deviation 6.9	-0.6 beats/min Standard Deviation 8.6	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 29	-0.5 beats/min Standard Deviation 11.4	0.7 beats/min Standard Deviation 8.3	1.3 beats/min Standard Deviation 8.2	-1.1 beats/min Standard Deviation 8.5	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 57	-2.1 beats/min Standard Deviation 11.0	0.9 beats/min Standard Deviation 8.9	2.5 beats/min Standard Deviation 9.7	1.1 beats/min Standard Deviation 11.1	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 85	-3.3 beats/min Standard Deviation 9.4	1.0 beats/min Standard Deviation 9.2	2.3 beats/min Standard Deviation 8.3	1.3 beats/min Standard Deviation 10.4	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 113	-1.8 beats/min Standard Deviation 9.8	0.5 beats/min Standard Deviation 10.1	0.2 beats/min Standard Deviation 8.7	0.2 beats/min Standard Deviation 10.7	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 122	-3.3 beats/min Standard Deviation 10.8	-1.2 beats/min Standard Deviation 13.4	-1.3 beats/min Standard Deviation 7.6	0.7 beats/min Standard Deviation 16.0	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 141	-1.3 beats/min Standard Deviation 10.4	0.8 beats/min Standard Deviation 9.2	2.0 beats/min Standard Deviation 9.4	2.2 beats/min Standard Deviation 10.4	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 169	0.7 beats/min Standard Deviation 10.1	0.5 beats/min Standard Deviation 11.0	3.0 beats/min Standard Deviation 8.8	1.5 beats/min Standard Deviation 9.7	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 197	2.1 beats/min Standard Deviation 12.5	2.3 beats/min Standard Deviation 9.8	1.7 beats/min Standard Deviation 9.5	1.8 beats/min Standard Deviation 10.4	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 225	0.9 beats/min Standard Deviation 10.0	1.2 beats/min Standard Deviation 11.0	2.5 beats/min Standard Deviation 10.1	1.8 beats/min Standard Deviation 10.4	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 253	-0.8 beats/min Standard Deviation 12.2	0.2 beats/min Standard Deviation 11.0	2.1 beats/min Standard Deviation 10.0	0.4 beats/min Standard Deviation 9.4	—	—
Vital Signs (Change in Heart Rate From Baseline) Variables Over Time Heart rate Day 325/405	0.5 beats/min Standard Deviation 10.4	1.3 beats/min Standard Deviation 9.8	1.9 beats/min Standard Deviation 9.4	0.7 beats/min Standard Deviation 9.9	—	—

SECONDARY outcome

Timeframe: From baseline to Day 325/405. Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325 respectively

Population: Randomized subjects who received any study treatment will be included in the As-treated Population. Subjects will be analysed according to the actual treatment they received, regardless of their randomized treatment group. Subjects treated within 250 mg group that received at least one 400 mg dose during the study will be analysed according to the 400mg group.

To assess the safety and tolerability of MEDI6570 compared with placebo

Outcome measures

Measure	MEDI6570 50 mg n=39 Participants Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 Participants Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 Participants Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	MEDI6570 150 mg or 400 mg n=126 Participants Participants received MEDI6570 150 mg or 400 mg every 4 weeks for 32 weeks	Placebo Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks	Total Overall Total
Vital Signs (Change of Weight From Baseline to Day 325/405 )	0.316 kg Standard Deviation 4.550	1.445 kg Standard Deviation 4.863	1.078 kg Standard Deviation 4.714	0.786 kg Standard Deviation 5.348	—	—

Adverse Events

MEDI6570 50 mg

Serious events: 4 serious events

Other events: 15 other events

Deaths: 0 deaths

MEDI6570 150 mg

Serious events: 17 serious events

Other events: 33 other events

Deaths: 1 deaths

MEDI6570 400 mg

Serious events: 10 serious events

Other events: 37 other events

Deaths: 1 deaths

Placebo

Serious events: 13 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	MEDI6570 50 mg n=39 participants at risk Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 participants at risk Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 participants at risk Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	Placebo n=126 participants at risk Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks
Cardiac disorders Coronary artery stenosis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Eye disorders Retinal detachment	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Diarrhoea	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Gastrointestinal polyp haemorrhage	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Ileal perforation	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Incarcerated umbilical hernia	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Inguinal hernia	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Omental necrosis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Acute myocardial infarction	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/129 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Pancreatitis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Vomiting	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
General disorders Non-cardiac chest pain	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Hepatobiliary disorders Bile duct stone	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Immune system disorders Anaphylactic reaction	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Covid-19	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Gastroenteritis	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Angina pectoris	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/129 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.4% 3/126 • Number of events 3 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Peritonitis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Urinary tract infection bacterial	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Urosepsis	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Angina unstable	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.3% 3/129 • Number of events 3 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Nervous system disorders Sciatica	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Nervous system disorders Transient ischaemic attack	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Renal and urinary disorders Stag horn calculus	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Skin and subcutaneous tissue disorders Psoriasis	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Vascular disorders Aortic aneurysm	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Atrial fibrillation	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Vascular disorders Peripheral artery occlusion	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Vascular disorders Peripheral ischaemia	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Cardiac arrest	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Cardiac failure	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Cardiogenic shock	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Coronary artery disease	0.00% 0/39 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/129 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.00% 0/126 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Other adverse events

Measure	MEDI6570 50 mg n=39 participants at risk Participants received MEDI6570 50 mg every 4 weeks for 32 weeks	MEDI6570 150 mg n=129 participants at risk Participants received MEDI6570 150 mg every 4 weeks for 32 weeks	MEDI6570 400 mg n=126 participants at risk Participants received MEDI6570 400 mg every 4 weeks for 32 weeks	Placebo n=126 participants at risk Participants received Placebo matched to MEDI6570 every 4 weeks for 32 weeks
Gastrointestinal disorders Diarrhoea	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.9% 5/129 • Number of events 5 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.4% 3/126 • Number of events 3 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Gastrointestinal disorders Nausea	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
General disorders Non-cardiac chest pain	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.9% 5/129 • Number of events 5 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	4.8% 6/126 • Number of events 8 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.2% 4/126 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
General disorders Pyrexia	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.4% 3/126 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Covid-19	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	6.2% 8/129 • Number of events 8 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	12.7% 16/126 • Number of events 17 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	4.8% 6/126 • Number of events 6 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Cardiac disorders Angina pectoris	2.6% 1/39 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	5.4% 7/129 • Number of events 7 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.4% 3/126 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.2% 4/126 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Infections and infestations Influenza	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.1% 4/129 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Musculoskeletal and connective tissue disorders Pain in extremity	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.3% 3/129 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.2% 4/126 • Number of events 5 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	2.4% 3/126 • Number of events 3 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	1.6% 2/126 • Number of events 4 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Vascular disorders Hypertension	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.1% 4/129 • Number of events 5 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	7.1% 9/126 • Number of events 9 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	7.1% 9/126 • Number of events 9 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.
Vascular disorders Hypotension	5.1% 2/39 • Number of events 2 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.78% 1/129 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	3.2% 4/126 • Number of events 5 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.	0.79% 1/126 • Number of events 1 • During study follow-up (from day 1 to day 325/405). Day 325/405: for participants who completed the study under CSP Amendment 1 & 2, the end of study visits were Day 405 and Day 325, respectively. Subjects initially randomized to the 250 mg group switched dose to 400 mg following CSP amendment 1 and were analysed according to the 400 mg group.

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator agrees to submit all manuscripts or abstracts to the sponsor for review before submission.
• Publication restrictions are in place

Restriction type: OTHER