Trial Outcomes & Findings for 16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis (NCT NCT01649375)

NCT ID: NCT01649375

Last Updated: 2019-10-30

Results Overview

ASAS 20 response is a validated composite assessment reflecting the percentage of treated patients who achieve within a defined timeframe an improvement of 20% and ≥1 unit on a scale of 1 to 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit in the remaining domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 219 participants
• Primary outcome timeframe: Baseline up to 16 weeks
• Results posted on: 2019-10-30

Participant Flow

Participant milestones

Measure	Secukinumab 75 mg Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16	Placebo - Secukinumab 75 mg Placebo patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16.	Placebo - Secukinumab 150 mg Placebo patients re-randomized to secukinumab 150 mg subcutaneous injection every 4 weeks starting from week 16.
Up to Week 16 STARTED	73	72	74	0	0
Up to Week 16 COMPLETED	68	66	66	0	0
Up to Week 16 NOT COMPLETED	5	6	8	0	0
Week 16 up to Week 260 STARTED	68	66	0	32	34
Week 16 up to Week 260 COMPLETED	48	53	0	20	29
Week 16 up to Week 260 NOT COMPLETED	20	13	0	12	5

Reasons for withdrawal

Measure	Secukinumab 75 mg Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16	Placebo - Secukinumab 75 mg Placebo patients re-randomized to secukinumab 75 mg subcutaneous injection every 4 weeks starting from week 16.	Placebo - Secukinumab 150 mg Placebo patients re-randomized to secukinumab 150 mg subcutaneous injection every 4 weeks starting from week 16.
Up to Week 16 Adverse Event	2	5	4	0	0
Up to Week 16 Lack of Efficacy	0	0	1	0	0
Up to Week 16 Physician Decision	0	0	1	0	0
Up to Week 16 Withdrawal by Subject	2	1	2	0	0
Up to Week 16 Death	1	0	0	0	0
Week 16 up to Week 260 Lack of Efficacy	7	4	0	4	2
Week 16 up to Week 260 Non-compliance	0	1	0	1	0
Week 16 up to Week 260 Physician Decision	0	2	0	0	0
Week 16 up to Week 260 Technical issues	0	1	0	1	0
Week 16 up to Week 260 Withdrawal by Subject	7	2	0	3	1
Week 16 up to Week 260 Death	1	1	0	0	0
Week 16 up to Week 260 Adverse Event	5	2	0	3	2

Baseline Characteristics

16 Week Efficacy and 5 Year Long Term Efficacy, Safety and Tolerability of Secukinumab in Patients With Active Ankylosing Spondylitis

Baseline characteristics by cohort

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16	Total n=219 Participants Total of all reporting groups
Age, Customized < 65 years	70 participants n=5 Participants	70 participants n=7 Participants	72 participants n=5 Participants	212 participants n=4 Participants
Age, Customized >= 65 to 74 years	2 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	5 participants n=4 Participants
Age, Customized >= 75 years	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	2 participants n=4 Participants
Sex: Female, Male Female	22 Participants n=5 Participants	26 Participants n=7 Participants	18 Participants n=5 Participants	66 Participants n=4 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	46 Participants n=7 Participants	56 Participants n=5 Participants	153 Participants n=4 Participants
Race/Ethnicity, Customized White	70 participants n=5 Participants	69 participants n=7 Participants	70 participants n=5 Participants	209 participants n=4 Participants
Race/Ethnicity, Customized Asian	3 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants	9 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline up to 16 weeks

ASAS 20 response is a validated composite assessment reflecting the percentage of treated patients who achieve within a defined timeframe an improvement of 20% and ≥1 unit on a scale of 1 to 10 in at least three of the four ASAS main domains and no worsening of ≥20% and ≥1 unit in the remaining domain. ASAS 20 is used to assess the efficacy of at least one dose of secukinumab against placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Percentage of Participants Achieving ASAS 20 (SpondyloArthritis International Society Criteria) Response at Week 16	41.1 percentage of participants	61.1 percentage of participants	28.4 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

ASAS 40 response is a validated composite assessment, reflecting the proportion of treated patients who achieve within a defined timeframe an improvement of ≥40% and ≥2 units on a scale of 0 to 10 (0 being worse and 10 being better) in at least three of the four ASAS main domains (patient global, pain, function and inflammation) and no worsening at all in the remaining domain.

ASAS 40 is used to assess the efficacy of at least one dose of secukinumab against placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Percentage of Participants Achieving ASAS 40 (SpondyloArthritis International Society Criteria) Response	26.0 percentage of participants	36.1 percentage of participants	10.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

The change from baseline in hsCRP is expressed as a ratio of post-baseline to baseline values. With the ratio normalized to 1.0 at baseline, ratios less than 1.0 represent decreased post-baseline values, whereas ratios greater than 1.0 represent increased post-baseline values. Blood levels of C-reactive protein (CRP), an acute phase reactant, are indicative of inflammation and of its severity, and can be used to monitor treatment response. A high sensitvity CRP (hsCRP) test is implemented in this study to assess the efficacy of at least one dose of secukinumab versus placebo in reducing AS elicited systemic inflammation over time.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Change From Baseline at Week 16 in Serum hsCRP	0.61 mg/L Standard Error 1.103	0.55 mg/L Standard Error 1.104	1.13 mg/L Standard Error 1.105

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

ASAS 5/6 response is a validated composite assessment, reflecting the percentage of treated patients who achieve within a defined timeframe at least 20% improvement in score in at least 5 of a conventional set of 6 clinical domains relevant to AS (pain, patient global assessment, function, inflammation, spinal mobility, C-reative protein) without deterioration in the 6th domain. In this study, ASAS 5/6 is used to assess the efficacy of at least one dose of secukinumab against placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Percentage of Participants Achieving ASAS 5/6 (SpondyloArthritis International Society Criteria) Response at Week 16	34.2 percentage of participants	43.1 percentage of participants	8.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

BASDAI is a validated assessment tool using 1 through 10 scales (1 indicating "no problem" and 10 indicating " worst problem"), to characterize six clinical domains (fatigue, spinal pain, joint pain/selling, localized tenderness, morning stiffness duration, morning stiffness severity) pertaining to five major symptoms of AS perceived by the patients. Computed composite scores of 4 or greater indicate suboptimal disease control. In this study, the BASDAI is used to assess the efficacy of at least one dose of secukinumab verus placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Change From Baseline at Week 16 for Total Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)	-1.92 scores on a scale Standard Error 0.249	-2.19 scores on a scale Standard Error 0.248	-0.85 scores on a scale Standard Error 0.252

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

Physical Function Component Summary (PCS) is only 1 component of SF-36. This scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Change From Baseline at Week 16 in Physical Function Component Summary (PCS) of the Medical Outcomes Study Questionnaire Short-form Health Survey (SF-36)	4.77 scores on a scale Standard Error 0.798	6.06 scores on a scale Standard Error 0.784	1.92 scores on a scale Standard Error 0.786

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

ASQoL is an 18 item questionnaire that assesses disease-specific quality of life (QoL), consisting of statements that are relevant to the physical and mental conditions for a participant with AS: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each statement is answered by the participant as a 'Yes' (scored as 1) or 'No' (scored as 0). All item scores are summed to give a total score. Total score can range from 0 (good QoL) to 18 (poor QoL). In this study, ASQoL is used to assess improvement from baseline of at least one dose of secukinumab versus placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Change From Baseline at Week 16 in ASQoL	-3.33 scores on a scale Standard Error 0.537	-4.00 scores on a scale Standard Error 0.528	-1.37 scores on a scale Standard Error 0.530

SECONDARY outcome

Timeframe: Baseline up to 16 weeks

ASAS partial remission is a composite assessment, reflecting the proportion of treated patients who achieve within a defined time frame a value not above 2 units in each of the 4 ASAS domains on a scale 0 to 10. In this study ASAS partial remission is used to assess the efficacy of at least one dose of secukinumab versus placebo.

Outcome measures

Measure	Secukinumab 75 mg n=73 Participants Secukinumab 75 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks.	Secukinumab 150 mg n=72 Participants Secukinumab 150 mg subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks	Placebo n=74 Participants Placebo subcutaneous injection once weekly at baseline, Weeks 1, 2, 3 and 4, followed by dosing every 4 weeks up to week 16
Percentage of Participants Achieving ASAS Partial Remission at Week 16	15.1 percentage of participants	13.9 percentage of participants	4.1 percentage of participants

Adverse Events

Any Secukinumab 75 mg

Serious events: 25 serious events

Other events: 76 other events

Deaths: 2 deaths

Any Secukinumab 150 mg

Serious events: 31 serious events

Other events: 99 other events

Deaths: 1 deaths

Placebo

Serious events: 4 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Measure	Any Secukinumab 75 mg n=105 participants at risk Includes patients originally randomized to secukinumab 75 mg at baseline and placebo patients who were re-randomized to secukinumab 75 mg at week 16 (AEs occurring after re-randomization).	Any Secukinumab 150 mg n=155 participants at risk Includes patients originally randomized to secukinumab 150 mg at baseline, placebo patients re-randomized to secukinumab 150 mg at Week 16 (AEs occuring after re-randomization) and patients who up-titrated from secukinumab 75 mg to 150 mg (AEs occurring after up-titration).	Placebo n=74 participants at risk Includes patients originally randomized to Placebo for AEs until the time of re-randomization (Week 16) to Secukinumab
Blood and lymphatic system disorders Iron deficiency anaemia	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Acute coronary syndrome	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Acute myocardial infarction	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Angina pectoris	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Atrioventricular block complete	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Coronary artery stenosis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Cardiac disorders Myocardial infarction	1.9% 2/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Eye disorders Iridocyclitis	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Eye disorders Iritis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Abdominal hernia	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Abdominal pain upper	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Anal fissure	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Colitis ischaemic	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Colitis microscopic	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Colitis ulcerative	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Crohn's disease	1.9% 2/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.3% 2/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Diarrhoea	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Gastrointestinal disorders Incarcerated hiatus hernia	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
General disorders Drug ineffective	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Hepatobiliary disorders Cholecystitis acute	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Hepatobiliary disorders Cholelithiasis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Immune system disorders Sarcoidosis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Anal abscess	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Arthritis bacterial	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Erysipelas	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Febrile infection	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Gallbladder abscess	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Gastroenteritis salmonella	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Groin abscess	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Influenza	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Meningitis viral	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Pharyngitis	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Pneumonia	1.9% 2/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.3% 2/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Postoperative wound infection	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Concussion	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Hip fracture	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Lower limb fracture	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Multiple injuries	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Rib fracture	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Spinal compression fracture	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Spinal cord injury cervical	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Injury, poisoning and procedural complications Splenic rupture	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Investigations Hepatic enzyme increased	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Back pain	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Foot deformity	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Osteoarthritis	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Paraganglion neoplasm	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Superficial spreading melanoma stage unspecified	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Carpal tunnel syndrome	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Headache	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.3% 2/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Ischaemic stroke	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.3% 2/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Quadriparesis	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Quadriplegia	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Transient ischaemic attack	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Psychiatric disorders Depression	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Renal and urinary disorders Nephrotic syndrome	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Renal and urinary disorders Stress urinary incontinence	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Reproductive system and breast disorders Vaginal haemorrhage	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Vascular disorders Haematoma	0.00% 0/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.65% 1/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Vascular disorders Peripheral arterial occlusive disease	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Vascular disorders Thrombophlebitis superficial	0.95% 1/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years

Other adverse events

Measure	Any Secukinumab 75 mg n=105 participants at risk Includes patients originally randomized to secukinumab 75 mg at baseline and placebo patients who were re-randomized to secukinumab 75 mg at week 16 (AEs occurring after re-randomization).	Any Secukinumab 150 mg n=155 participants at risk Includes patients originally randomized to secukinumab 150 mg at baseline, placebo patients re-randomized to secukinumab 150 mg at Week 16 (AEs occuring after re-randomization) and patients who up-titrated from secukinumab 75 mg to 150 mg (AEs occurring after up-titration).	Placebo n=74 participants at risk Includes patients originally randomized to Placebo for AEs until the time of re-randomization (Week 16) to Secukinumab
Gastrointestinal disorders Diarrhoea	8.6% 9/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	11.0% 17/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
General disorders Fatigue	3.8% 4/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	3.2% 5/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	6.8% 5/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Bronchitis	14.3% 15/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	9.0% 14/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Gastroenteritis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	8.4% 13/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Influenza	12.4% 13/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	9.0% 14/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Nasopharyngitis	28.6% 30/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	22.6% 35/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	4.1% 3/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Oral herpes	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.2% 8/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Pharyngitis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.9% 3/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Rhinitis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	3.2% 5/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Sinusitis	4.8% 5/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.2% 8/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Upper respiratory tract infection	12.4% 13/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	10.3% 16/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.7% 2/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Infections and infestations Urinary tract infection	4.8% 5/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.8% 9/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.7% 2/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Metabolism and nutrition disorders Hyperlipidaemia	4.8% 5/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.2% 8/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Ankylosing spondylitis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	3.9% 6/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Arthralgia	7.6% 8/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	6.5% 10/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.7% 2/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Back pain	6.7% 7/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	8.4% 13/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.7% 2/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Bursitis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.6% 4/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.7% 7/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.2% 8/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Osteoarthritis	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.6% 4/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Musculoskeletal and connective tissue disorders Pain in extremity	1.9% 2/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	7.1% 11/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Dizziness	1.9% 2/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.9% 3/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.4% 4/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Nervous system disorders Headache	8.6% 9/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	9.7% 15/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	8.1% 6/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Respiratory, thoracic and mediastinal disorders Cough	4.8% 5/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	7.1% 11/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.8% 4/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	5.2% 8/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.7% 2/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Skin and subcutaneous tissue disorders Rash	5.7% 6/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	2.6% 4/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	1.4% 1/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years
Vascular disorders Hypertension	8.6% 9/105 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	9.7% 15/155 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years	0.00% 0/74 • Adverse Events and Serious Adverse Events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately up to 5.5 years

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial
• Publication restrictions are in place

Restriction type: OTHER