OPTIMISE: Plaque Psoriasis Efficacy and Safety With Secukinumab

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02409667
• Collaborator: (none)
• Enrollment: 16,487
• Locations: 200
• Arms: 4
• Actual Duration (Months): 24
• Patients Per Site: 82.4
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

To demonstrate in the patient pool of PASI 90 responders at Week 24 that secukinumab 300 mg s.c. when administered at a longer dosing interval is non-inferior to secukinumab 300 mg s.c. every 4 weeks treatment with respect to maintaining a PASI 90 response rate at Week 52.

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Biological: Secukinumab	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 16487 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Long Term Clear Skin Maintenance Treatment Optimization in Patients With Moderate to Severe Chronic Plaque Psoriasis: A Randomized, Multicenter, Open-label With Blinded-assessment, Comparative, 52 Week Study to Evaluate the Efficacy, Safety and Tolerability of Secukinumab 300 mg s.c.
• Actual Study Start Date: May 7, 2015
• Actual Primary Completion Date: Mar 14, 2017
• Actual Study Completion Date: May 8, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Secukinumab 300mg in PASI 90 responders (every 4 weeks) Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg subcutanous (s.c.) every 4 weeks were treated with Secukinumab 300 mg subcutanous (s.c.) from week 24 until Week 52 every 4 weeks.	Biological: Secukinumab; Secukinumab for s.c. injection was supplied in single boxes each containing 2 pre-filled syringes (PFS) of 150 mg secukinumab in a 1 mL liquid formulation. Each 300 mg dose was administered as 2 PFS injections of 150 mg secukinumab.
Experimental: Secukinumab 300mg in PASI 90 responders (longer intervals) Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg subcutanous (s.c.) every 4 weeks were treated with Secukinumab 300 mg subcutanous (s.c.) from week 24 until Week 52 every 6 weeks.	Biological: Secukinumab; Secukinumab for s.c. injection was supplied in single boxes each containing 2 pre-filled syringes (PFS) of 150 mg secukinumab in a 1 mL liquid formulation. Each 300 mg dose was administered as 2 PFS injections of 150 mg secukinumab.
Experimental: Secukinumab 300mg in PASI 75-90 responders (every 4 weeks) Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg subcutanous (s.c.) every 4 weeks will be treated with Secukinumab 300 mg subcutanous (s.c.) from week 24 until Week 52 every 4 weeks.	Biological: Secukinumab; Secukinumab for s.c. injection was supplied in single boxes each containing 2 pre-filled syringes (PFS) of 150 mg secukinumab in a 1 mL liquid formulation. Each 300 mg dose was administered as 2 PFS injections of 150 mg secukinumab.
Active Comparator: Secukinumab 300mg in PASI 75-90 responders (shorter intervals) Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg subcutanous (s.c.) every 4 weeks were treated with Secukinumab 300 mg subcutanous (s.c.) from week 24 until Week 52 every 2 weeks.	Biological: Secukinumab; Secukinumab for s.c. injection was supplied in single boxes each containing 2 pre-filled syringes (PFS) of 150 mg secukinumab in a 1 mL liquid formulation. Each 300 mg dose was administered as 2 PFS injections of 150 mg secukinumab.

Outcome Measures

Primary Outcome Measures

1. Maintenance of PASI 90 Response at Week 52 in Participants With a PASI 90 Response at Week 24 [Week 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

Secondary Outcome Measures

1. Key Secondary: PASI 90 Response Rate at Week 52 in Participants With a PASI Response of ≥75 to <90 at Week 24 [Week 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).

2. PASI 50, PASI 75, PASI 100 and IGA Mod 2011 0 or 1 Responders at Week 52 in Participants With a PASI 90 Response at Week 24 [week 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.

3. PASI 50, PASI 75, PASI 100 and IGA Mod 2011 0 or 1 Responders at Week 52 in Participants With a PASI Response of ≥75 to <90 at Week 24 [Week 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.

4. Change From Baseline in PASI in Participants With a PASI 90 Response at Week 24 [Baseline, Weeks 28, 32, 36, 40, 44, 48 and 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative change from baseline indicates improvement.

5. Change From Baseline in PASI in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Weeks 28, 32, 36, 40, 44, 48 and 52]

   PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative change from baseline indicates improvement.

6. Change From Baseline in DLQI in Participants With a PASI 90 Response at Week 24 [Baseline, Week 52]

   The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

7. Change From Baseline in DLQI in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Week 52]

   The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.

8. Change From Baseline in Work Productivity and Activity Impairment Questionnaire - Psoriasis (WPAI-PSO) Score in Participants With a PASI 90 Response at Week 24 [Baseline, Week 52]

   The WPAI-PSO is a self-administered questionnaire comprised of 6 questions about effects of psoriasis on the patient's ability to work and perform regular activities based on the previous 7 days. The questionnaire quantifies the number of hours the respondent was unable to work and evaluates how much the respondent's psoriasis affected productivity while working. For respondents who were not in paid employment, the questionnaire evaluated how much the respondent's psoriasis affects their ability to perform regular daily activities. Four outcomes were generated from the WPAI-PSO: % Absenteeism: percent work time missed due to health; % Presenteism: percent impairment while working due to health; % Total work productivity impairment: percent overall work impairment due to health; % Total activity impairment: percent activity impairment due to health for all respondents. First 3 outcomes applied to employed participants only. A negative change from baseline indicates improvement.

9. Change From Baseline in WPAI-PSO Score in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Week 52]

   The WPAI-PSO is a self-administered questionnaire comprised of 6 questions about effects of psoriasis on the patient's ability to work and perform regular activities based on the previous 7 days. The questionnaire quantifies the number of hours the respondent was unable to work and evaluates how much the respondent's psoriasis affected productivity while working. For respondents who were not in paid employment, the questionnaire evaluated how much the respondent's psoriasis affects their ability to perform regular daily activities. Four outcomes were generated from the WPAI-PSO: % Absenteeism: percent work time missed due to health; % Presenteism: percent impairment while working due to health; % Total work productivity impairment: percent overall work impairment due to health; % Total activity impairment: percent activity impairment due to health for all respondents. First 3 outcomes applied to employed participants only. A negative change from baseline indicates improvement.

10. Change From Baseline in Pain, Itching and Scaling Score in Participants With a PASI 90 Response at Week 24 [Baseline, Week 52]

    Self-administered, 11-point numeric rating scales (NRS, 0-10) were used to evaluate the patients' assessment of their current pain, itching and scaling. Respondents answered the following questions for the assessment: Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours?; Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours?; and Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours? Patients had to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the understanding that the 0 represents the absence or null end of the pain, itching, or scale intensity (i.e. no pain, itching or scaling) and the 10 represents the other extreme of pain, itching, or scaling intensity (i.e. pain, itching or scaling as bad as it could be). The number that the patient selected represents his or her intensity score in the respective category. A negative change from baseline indicates improvement

11. Change From Baseline in Pain, Itching and Scaling Score in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Week 52]

    Self-administered, 11-point numeric rating scales (NRS, 0-10) were used to evaluate the patients' assessment of their current pain, itching and scaling. Respondents answered the following questions for the assessment: Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours?; Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours?; and Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours? Patients had to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the understanding that the 0 represents the absence or null end of the pain, itching, or scale intensity (i.e. no pain, itching or scaling) and the 10 represents the other extreme of pain, itching, or scaling intensity (i.e. pain, itching or scaling as bad as it could be). The number that the patient selected represents his or her intensity score in the respective category. A negative change from baseline indicates improvement

12. Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) in Participants With a PASI 90 Response at Week 24 [Baseline, Week 52]

    A visual analogue scale (VAS) was used within the EQ-5D. This scale recorded the respondent's self-rated health on a vertical 20-cm VAS where the endpoints were labeled "best imaginable health state" and "worst imaginable health state." This resulted in a numeric value set ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state"). A positive change from baseline indicates improvement.

13. Change From Baseline in the EQ-5D VAS in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Week 52]

    A visual analogue scale (VAS) was used within the EQ-5D. This scale recorded the respondent's self-rated health on a vertical 20-cm VAS where the endpoints were labeled "best imaginable health state" and "worst imaginable health state." This resulted in a numeric value set ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state").

14. Change From Baseline in the EQ-5D Utility Index (Germany, United Kingdom (UK)) in Participants With a PASI 90 Response at Week 24 [Baseline, Week 52]

    The EQ-5D quantifies the health state of a patient for the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. In this study the EQ-5D-5L version has been used which evaluates each of these dimensions using the following 5 labels: no problems, slight problems, moderate problems, severe problems & unable to/extreme problems. Based on the 5 dimensions, a summary score (utility index) was derived using country specific value sets evaluating the patient condition described by the outcome in the single dimensions. The EQ-5D-5L (in this trail) utility index based on the crosswalk value sets available from the EuroQol for Germany & UK (https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/) was calculated. A positive change from baseline indicates improvement. A visual analogue scale was used within the EQ-5D measuring the health state of the patients, ranging from 0 (worst imaginable health state) up to 100 (best imaginable health state).

15. Change From Baseline in the EQ-5D Utility Index (Germany, UK) in Participants With a PASI Response of ≥75 to <90 at Week 24 [Baseline, Week 52]

    The EQ-5D quantifies the health state of a patient for the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. In the current study the EQ-5D-5L version has been used which evaluates each of these dimensions using the following five labels: "no problems", "slight problems", "moderate problems", "severe problems" and "unable to/extreme problems". Based on the five dimensions, a summary score (utility index) was derived using country specific value sets evaluating the patient condition described by the outcome in the single dimensions. For this trial, the EQ-5D-5L utility index based on the crosswalk value sets available from the EuroQol for Germany and for UK (https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/) was calculated. A visual analogue scale (VAS) was used within the EQ-5D measuring the health state of the patients, ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state").

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Main Inclusion Criteria:

1. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to Screening and candidate for systemic therapy.

2. Moderate to severe psoriasis at Baseline as evidenced by:

• PASI ≥ 10 and

• IGA mod 2011 score of 3 or higher (based on a scale of 0 to 4) and

• BSA affected by plaque-type psoriasis of ≥ 10%.

Main Exclusion Criteria:

1. History of exposure to any biologic drug taken for the treatment of chronic plaque psoriasis or any other indication including but not limited to anti-tumor necrosis factor (TNF) alpha, anti interleukin (IL)12/23, or any anti-IL 17A or IL 17A receptor (IL 17AR) antibody.

2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes.

3. Forms of psoriasis other than chronic plaque-type (eg, pustular, erythrodermic and guttate psoriasis).

4. Drug-induced psoriasis (ie, new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).

5. Ongoing use of prohibited psoriasis treatments (eg, topical or systemic corticosteroids, ultraviolet (UV) therapy).

6. Ongoing use of other non-psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to. All other prior non-psoriasis concomitant treatments must be at a stable dose as detailed in the protocol before initiation of study drug.

7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).

8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study drug and for 16 weeks after stopping study drug.

9. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy.

10. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions) which, in the opinion of the Investigator, significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Innsbruck		Austria	6020
2	Novartis Investigative Site	Linz		Austria	A-4020
3	Novartis Investigative Site	Wien		Austria	1090
4	Novartis Investigative Site	Wien		Austria	A 1090
5	Novartis Investigative Site	Jette	Brussel	Belgium	1090
6	Novartis Investigative Site	Bruxelles		Belgium	1070
7	Novartis Investigative Site	Bruxelles		Belgium	1200
8	Novartis Investigative Site	Gent		Belgium	9000
9	Novartis Investigative Site	Liege		Belgium	4000
10	Novartis Investigative Site	Loverval		Belgium	6280
11	Novartis Investigative Site	Sofia	BGR	Bulgaria	1431
12	Novartis Investigative Site	Pleven		Bulgaria	5800
13	Novartis Investigative Site	Plovdiv		Bulgaria	4002
14	Novartis Investigative Site	Sofia		Bulgaria	1404
15	Novartis Investigative Site	Sofia		Bulgaria	1407
16	Novartis Investigative Site	Stara Zagora		Bulgaria	6000
17	Novartis Investigative Site	Varna		Bulgaria	9000
18	Novartis Investigative Site	Ivanic Grad		Croatia	10310
19	Novartis Investigative Site	Osijek		Croatia	31000
20	Novartis Investigative Site	Zagreb		Croatia	10000
21	Novartis Investigative Site	Brno	Czech Republic	Czechia	656 91
22	Novartis Investigative Site	Ostrava Poruba	Czech Republic	Czechia	708 52
23	Novartis Investigative Site	Prague 8	Czech Republic	Czechia	180 00
24	Novartis Investigative Site	Olomouc		Czechia	775 20
25	Novartis Investigative Site	Praha 10		Czechia	100 34
26	Novartis Investigative Site	Praha		Czechia	12808
27	Novartis Investigative Site	Arhus C		Denmark	DK-8000
28	Novartis Investigative Site	Hellerup		Denmark	DK-2900
29	Novartis Investigative Site	Tampere		Finland	33100
30	Novartis Investigative Site	Turku		Finland	FIN-20100
31	Novartis Investigative Site	Le Mans	Cedex 09	France	72037
32	Novartis Investigative Site	Bordeaux Cedex		France	33075
33	Novartis Investigative Site	Dijon		France	21079
34	Novartis Investigative Site	Grenoble		France	38043
35	Novartis Investigative Site	Lille		France	59000
36	Novartis Investigative Site	Montpellier cedex 5		France	34295
37	Novartis Investigative Site	Nice		France	06202
38	Novartis Investigative Site	Rouen		France	76031
39	Novartis Investigative Site	Saint-Etienne		France	42055
40	Novartis Investigative Site	Toulouse Cedex		France	31400
41	Novartis Investigative Site	Trevenans		France	90400
42	Novartis Investigative Site	Vandoeuvre Les Nancy		France	54511
43	Novartis Investigative Site	Augsburg		Germany	86179
44	Novartis Investigative Site	Berlin		Germany	10117
45	Novartis Investigative Site	Berlin		Germany	10783
46	Novartis Investigative Site	Bochum		Germany	44793
47	Novartis Investigative Site	Bonn		Germany	53105
48	Novartis Investigative Site	Braunschweig		Germany	38100
49	Novartis Investigative Site	Dresden		Germany	01069
50	Novartis Investigative Site	Dresden		Germany	01307
51	Novartis Investigative Site	Duesseldorf		Germany	40212
52	Novartis Investigative Site	Duesseldorf		Germany	D 40225
53	Novartis Investigative Site	Frankfurt		Germany	60590
54	Novartis Investigative Site	Goettingen		Germany	37075
55	Novartis Investigative Site	Hamburg		Germany	20246
56	Novartis Investigative Site	Hamburg		Germany	20354
57	Novartis Investigative Site	Hamburg		Germany	22391
58	Novartis Investigative Site	Hanau		Germany	63450
59	Novartis Investigative Site	Leipzig		Germany	04103
60	Novartis Investigative Site	Lubeck		Germany	23538
61	Novartis Investigative Site	Muenchen		Germany	81377
62	Novartis Investigative Site	Muenchen		Germany	81675
63	Novartis Investigative Site	Muenster		Germany	48149
64	Novartis Investigative Site	Osnabrueck		Germany	49074
65	Novartis Investigative Site	Pommelsbrunn		Germany	91224
66	Novartis Investigative Site	Schwerin		Germany	19055
67	Novartis Investigative Site	Stade		Germany	21682
68	Novartis Investigative Site	Stuttgart		Germany	70178
69	Novartis Investigative Site	Ulm		Germany	89081
70	Novartis Investigative Site	Larissa	GR	Greece	411 10
71	Novartis Investigative Site	Thessaloniki	GR	Greece	546 29
72	Novartis Investigative Site	Athens		Greece	161 21
73	Novartis Investigative Site	Thessaloniki		Greece	546 43
74	Novartis Investigative Site	Kecskemet	Bacs Kiskun	Hungary	6000
75	Novartis Investigative Site	Budapest		Hungary	1085
76	Novartis Investigative Site	Debrecen		Hungary	4032
77	Novartis Investigative Site	Kaposvar		Hungary	7400
78	Novartis Investigative Site	Pecs		Hungary	7632
79	Novartis Investigative Site	Szeged		Hungary	6725
80	Novartis Investigative Site	Afula		Israel	1834111
81	Novartis Investigative Site	Haifa		Israel	3109601
82	Novartis Investigative Site	Petach Tikva		Israel	49100
83	Novartis Investigative Site	Ramat Gan		Israel	5265601
84	Novartis Investigative Site	Tel Aviv		Israel	64239
85	Novartis Investigative Site	Bolzano	BZ	Italy	39100
86	Novartis Investigative Site	Messina	ME	Italy	98125
87	Novartis Investigative Site	Modena	MO	Italy	41124
88	Novartis Investigative Site	Palermo	PA	Italy	90127
89	Novartis Investigative Site	Roma	RM	Italy	00189
90	Novartis Investigative Site	Daugavpils	LVA	Latvia	LV-5404
91	Novartis Investigative Site	Riga	LVA	Latvia	LV-1003
92	Novartis Investigative Site	Ventspils	LVA	Latvia	LV-3601
93	Novartis Investigative Site	Riga		Latvia	1012
94	Novartis Investigative Site	Riga		Latvia	LV-1001
95	Novartis Investigative Site	Kaunas	LTU	Lithuania	LT 50161
96	Novartis Investigative Site	Klaipeda	LTU	Lithuania	92304
97	Novartis Investigative Site	Kaunas	LT	Lithuania	47144
98	Novartis Investigative Site	Vilnius		Lithuania	LT-07195
99	Novartis Investigative Site	Vilnius		Lithuania	LT-08661
100	Novartis Investigative Site	Breda	CK	Netherlands	4818
101	Novartis Investigative Site	Alkmaar		Netherlands	1817 MS
102	Novartis Investigative Site	Almere		Netherlands	1315 RA
103	Novartis Investigative Site	Bergen op Zoom		Netherlands	4624 VT
104	Novartis Investigative Site	Geldrop		Netherlands	5664 EH
105	Novartis Investigative Site	Leiderdorp		Netherlands	2353 GA
106	Novartis Investigative Site	Sittard-Geleen		Netherlands	6162 BG
107	Novartis Investigative Site	Voorburg		Netherlands	2275 CX
108	Novartis Investigative Site	Kraków		Poland	31-501
109	Novartis Investigative Site	Lodz		Poland	90-265
110	Novartis Investigative Site	Lodz		Poland	90-436
111	Novartis Investigative Site	Lublin		Poland	20-079
112	Novartis Investigative Site	Olsztyn		Poland	10-045
113	Novartis Investigative Site	Ossy		Poland	42 624
114	Novartis Investigative Site	Poznan		Poland	60 529
115	Novartis Investigative Site	Warszawa		Poland	02-507
116	Novartis Investigative Site	Warszawa		Poland	04141
117	Novartis Investigative Site	Wroclaw		Poland	50-368
118	Novartis Investigative Site	Braga		Portugal	4710243
119	Novartis Investigative Site	Coimbra		Portugal	3000 075
120	Novartis Investigative Site	Leiria		Portugal	2410-187
121	Novartis Investigative Site	Porto		Portugal	4099-001
122	Novartis Investigative Site	Porto		Portugal	4200 319
123	Novartis Investigative Site	Vila Nova de Gaia		Portugal	4434 502
124	Novartis Investigative Site	Chelyabinsk		Russian Federation	454092
125	Novartis Investigative Site	Kazan		Russian Federation	420012
126	Novartis Investigative Site	Moscow		Russian Federation	107076
127	Novartis Investigative Site	Rostov on Don region		Russian Federation	346880
128	Novartis Investigative Site	Saint-Petersburg		Russian Federation	194021
129	Novartis Investigative Site	Saint-Petersburg		Russian Federation	194044
130	Novartis Investigative Site	Bojnice		Slovakia	972 01
131	Novartis Investigative Site	Bratislava		Slovakia	841 04
132	Novartis Investigative Site	Kosice		Slovakia	04001
133	Novartis Investigative Site	Povazska Bystrica		Slovakia	017 26
134	Novartis Investigative Site	Svidnik		Slovakia	08901
135	Novartis Investigative Site	Villajoyosa	Alicante	Spain	703570
136	Novartis Investigative Site	Cordoba	Andalucia	Spain	14004
137	Novartis Investigative Site	Granada	Andalucia	Spain	18016
138	Novartis Investigative Site	Malaga	Andalucia	Spain	29009
139	Novartis Investigative Site	Malaga	Andalucia	Spain	29010
140	Novartis Investigative Site	Sevilla	Andalucia	Spain	41009
141	Novartis Investigative Site	Sevilla	Andalucia	Spain	41013
142	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona	Spain	08907
143	Novartis Investigative Site	Sabadell	Barcelona	Spain	08208
144	Novartis Investigative Site	Sant Joan Despi	Barcelona	Spain	08970
145	Novartis Investigative Site	Santander	Cantabria	Spain	39008
146	Novartis Investigative Site	Leon	Castilla Y Leon	Spain	24071
147	Novartis Investigative Site	Salamanca	Castilla Y Leon	Spain	37007
148	Novartis Investigative Site	Badalona	Catalunya	Spain	08916
149	Novartis Investigative Site	Barcelona	Catalunya	Spain	08003
150	Novartis Investigative Site	Barcelona	Catalunya	Spain	08035
151	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
152	Novartis Investigative Site	Alicante	Comunidad Valenciana	Spain	03010
153	Novartis Investigative Site	Castellon	Comunidad Valenciana	Spain	12005
154	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46014
155	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46015
156	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46017
157	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46026
158	Novartis Investigative Site	La Coruna	Galicia	Spain	15006
159	Novartis Investigative Site	Santiago de Compostela	Galicia	Spain	15706
160	Novartis Investigative Site	Palma de Mallorca	Islas Baleares	Spain	07014
161	Novartis Investigative Site	Las Palmas de Gran Canaria	Las Palmas De G.C	Spain	35010
162	Novartis Investigative Site	Alcorcon	Madrid	Spain	28922
163	Novartis Investigative Site	Fuenlabrada	Madrid	Spain	28942
164	Novartis Investigative Site	San Sebastian de los Reyes	Madrid	Spain	28702
165	Novartis Investigative Site	Pamplona	Navarra	Spain	31008
166	Novartis Investigative Site	Bilbao	Pais Vasco	Spain	48013
167	Novartis Investigative Site	La Laguna	Santa Cruz De Tenerife	Spain	38320
168	Novartis Investigative Site	Alzira	Valencia	Spain	46600
169	Novartis Investigative Site	Manises	Valencia	Spain	46940
170	Novartis Investigative Site	Baracaldo	Vizcaya	Spain	48903
171	Novartis Investigative Site	Barcelona		Spain	08041
172	Novartis Investigative Site	Huesca		Spain	22004
173	Novartis Investigative Site	Madrid		Spain	28006
174	Novartis Investigative Site	Madrid		Spain	28007
175	Novartis Investigative Site	Madrid		Spain	28031
176	Novartis Investigative Site	Madrid		Spain	28034
177	Novartis Investigative Site	Madrid		Spain	28041
178	Novartis Investigative Site	Madrid		Spain	28046
179	Novartis Investigative Site	Madrid		Spain	28222
180	Novartis Investigative Site	Mallorca		Spain	07500
181	Novartis Investigative Site	Murcia		Spain	30003
182	Novartis Investigative Site	Pontevedra		Spain	36003
183	Novartis Investigative Site	Zaragoza		Spain	50009
184	Novartis Investigative Site	Falun		Sweden	791 82
185	Novartis Investigative Site	Malmo		Sweden	SE-205 02
186	Novartis Investigative Site	Stockholm		Sweden	171 76
187	Novartis Investigative Site	Stockholm		Sweden	SE-118 83
188	Novartis Investigative Site	Uppsala		Sweden	751 85
189	Novartis Investigative Site	Basel		Switzerland	4031
190	Novartis Investigative Site	Geneve		Switzerland	1211
191	Novartis Investigative Site	Lausanne		Switzerland	1011
192	Novartis Investigative Site	Zuerich		Switzerland	8091
193	Novartis Investigative Site	Canterbury	Kent	United Kingdom	CT1 3NG
194	Novartis Investigative Site	Salford	Manchester	United Kingdom	M6 8HD
195	Novartis Investigative Site	Cliftonville	Northampton	United Kingdom	NN1 5BD
196	Novartis Investigative Site	Cannock	Staffordshire	United Kingdom	WS11 2XY
197	Novartis Investigative Site	Dudley	West Midlands	United Kingdom	DY1 2HQ
198	Novartis Investigative Site	Leeds	West Yorkshire	United Kingdom	LS7 4SA
199	Novartis Investigative Site	Cambridge		United Kingdom	CB7 5JD
200	Novartis Investigative Site	Harrogate		United Kingdom	HG2 7SX

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis

Study Documents (Full-Text)

• Statistical Analysis Plan - May 22, 2017
• Study Protocol - Jun 16, 2015

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02409667
• Other Study ID Numbers: CAIN457A3302
• First Posted: Apr 7, 2015
• Last Update Posted: May 13, 2019
• Last Verified: Feb 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: plaque, psoriasis
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Pre-assignment Detail	The screening period was up to 4 weeks and rescreening was allowed for an unlimited number of times. At the Screening Visit, every patient was registered in an Interactive Response Technology and the Investigator ensured that the patient fulfilled all the inclusion/exclusion criteria

Arm/Group Title	Treatment Period 1: All Participants	Treatment Period 2: Group 1	Treatment Period 2: Group 2	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants received secukinumab 300 mg subcutaneous (s.c.) every 4 weeks for 24 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Period Title: Treatment Period 1, Baseline to Week 24
STARTED	1647	0	0	0	0
COMPLETED	1526	0	0	0	0
NOT COMPLETED	121	0	0	0	0
Period Title: Treatment Period 1, Baseline to Week 24
STARTED	0	644	662	114	93
COMPLETED	0	621	641	106	90
NOT COMPLETED	0	23	21	8	3

Baseline Characteristics

Arm/Group Title	Treatment Period 1: All Participants
Arm/Group Description	Participants received secukinumab 300 mg subcutaneous (s.c.) every 4 weeks for 24 weeks.
Overall Participants	1647
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.1 (13.38)
Sex: Female, Male (Count of Participants)
Female	476 28.9%
Male	1171 71.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	16 1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 0.2%
White	1597 97%
More than one race	0 0%
Unknown or Not Reported	30 1.8%

Outcome Measures

1. Primary Outcome

Title	Maintenance of PASI 90 Response at Week 52 in Participants With a PASI 90 Response at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Full analysis set for Treatment Period 2 of PASI 90 responders (FAS-P90R): The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	644	662
Count of Participants [Participants]	552 33.5%	496 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The statistical null-hypothesis to be rejected in the primary analysis was that the odds ratio of maintaining a PASI 90 response for patients with secukinumab 4-weekly dosing versus patients on secukinumab 6-weekly dosing exceeds the non-inferiority margin of 1+δ.
Statistical Test of Hypothesis	p-Value	0.1499
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.91
	Confidence Interval	(2-Sided) 95%; 1.44 to 2.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Key Secondary: PASI 90 Response Rate at Week 52 in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4).
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

FAS for Treatment Period 2 of PASI 75 responders who did not achieve a PASI 90 response (FAS-P75R): All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at the Week 24 visit, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	114	92
Count of Participants [Participants]	53 3.2%	52 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1013
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.35 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	PASI 50, PASI 75, PASI 100 and IGA Mod 2011 0 or 1 Responders at Week 52 in Participants With a PASI 90 Response at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.
Time Frame	week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R with evaluable data were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	644	662
PASI 50	608 36.9%	624 NaN
PASI 75	597 36.2%	588 NaN
PASI 90	553 33.6%	496 NaN
PASI 100	378 23%	305 NaN
IGA mod 2011	564 34.2%	529 NaN

4. Secondary Outcome

Title	PASI 50, PASI 75, PASI 100 and IGA Mod 2011 0 or 1 Responders at Week 52 in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72 (maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). PASI 50, 75, 90 and 100 were defined as participants achieving ≥ 50%, 75%, 90% or 100% improvement from baseline. The IGA mod 2011 scale is static, i.e. it referred exclusively to the participant's disease at the time of the assessment, and did not compare with any of the participant's previous disease states at previous visits. The scores are: 0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe.
Time Frame	Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P75R with evaluable data were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at the Week 24 visit, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	104	90
PASI 50	98 6%	88 NaN
PASI 75	74 4.5%	80 NaN
PASI 90	53 3.2%	52 NaN
PASI 100	12 0.7%	13 NaN
IGA mod 2011 0 or 1	64 3.9%	72 NaN

5. Secondary Outcome

Title	Change From Baseline in PASI in Participants With a PASI 90 Response at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative change from baseline indicates improvement.
Time Frame	Baseline, Weeks 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and the post-baseline time point, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	644	662
Week 28	-20.7 (8.471)	-19.9 (8.511)
Week 32	-20.7 (8.581)	-19.8 (8.474)
Week 36	-20.6 (8.439)	-19.7 (8.563)
Week 40	-20.5 (8.392)	-19.6 (8.393)
Week 44	-20.5 (8.384)	-19.6 (8.484)
Week 48	-20.5 (8.472)	-19.2 (8.509)
Week 52	-20.4 (8.301)	-19.2 (8.513)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 28
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0489
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least square mean (LSM) estimate
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.18 to -0.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1073
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.37 to -0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 40
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.38 to -0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 44
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.45 to -0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.70 to -0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0000
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM mean
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 95%; -0.81 to -0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in PASI in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	PASI is a combined assessment of lesion severity and affected area into a single score: 0 (no disease) to 72(maximal disease). Body is divided into 4 areas for scoring (head, arms, trunk, legs; each area is scored by itself and scores are combined for final PASI. For each area, percent of skin involved is estimated: 0 (0%) to 6 (90-100%), and severity is estimated by clinical signs, erythema, induration and desquamation; scale 0 (none) to 4 (maximum). Final PASI = sum of severity parameters for each area* area score weight of section (head: 0.1, arms: 0.2 body: 0.3 legs: 0.4). A negative change from baseline indicates improvement.
Time Frame	Baseline, Weeks 28, 32, 36, 40, 44, 48 and 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and the post-baseline time point, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	114	92
Week 28	-16.1 (6.160)	-16.3 (8.029)
Week 32	-15.9 (6.002)	-16.6 (7.941)
Week 36	-16.1 (6.356)	-16.6 (7.996)
Week 40	-16.1 (6.908)	-16.8 (8.170)
Week 44	-16.1 (6.553)	-16.6 (8.259)
Week 48	-15.6 (6.246)	-16.8 (8.307)
Week 52	-15.5 (6.371)	-16.6 (8.011)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 28
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1740
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0287
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 95%; 0.08 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1202
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; -0.16 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 40
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1157
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.19 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 44
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3189
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95%; -0.52 to 1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0240
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Week 52
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0090
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	1.47
	Confidence Interval	(2-Sided) 95%; 0.37 to 2.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in DLQI in Participants With a PASI 90 Response at Week 24
Description	The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and week 52, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	605	624
Mean (Standard Deviation) [score on a scale]	-12.7 (7.325)	-11.4 (7.480)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -0.93 to -0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in DLQI in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases such as eczema, psoriasis, acne and viral worts. It is a self-administered questionnaire which includes domains of daily activity, leisure, personal relationships, symptoms and feelings, treatment and school/work activities. Each domain has 4 response categories ranging from 0 (not at all) to 3 (very much). "Not relevant" is a valid score also and is scored as 0. The DLQI total score is a sum of all 10 responses. Scores range from 0 to 30 with higher scores indicating greater health-related quality of life impairment. A negative mean percentage change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and week 52, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	105	89
Mean (Standard Deviation) [score on a scale]	-10.0 (6.605)	-9.72 (6.880)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0675
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; -0.09 to 2.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment Questionnaire - Psoriasis (WPAI-PSO) Score in Participants With a PASI 90 Response at Week 24
Description	The WPAI-PSO is a self-administered questionnaire comprised of 6 questions about effects of psoriasis on the patient's ability to work and perform regular activities based on the previous 7 days. The questionnaire quantifies the number of hours the respondent was unable to work and evaluates how much the respondent's psoriasis affected productivity while working. For respondents who were not in paid employment, the questionnaire evaluated how much the respondent's psoriasis affects their ability to perform regular daily activities. Four outcomes were generated from the WPAI-PSO: % Absenteeism: percent work time missed due to health; % Presenteism: percent impairment while working due to health; % Total work productivity impairment: percent overall work impairment due to health; % Total activity impairment: percent activity impairment due to health for all respondents. First 3 outcomes applied to employed participants only. A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and week 52, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	644	662
Absenteeism	-4.70 (19.590)	-1.99 (19.759)
Presenteeism	-23.1 (25.968)	-23.0 (26.522)
Total activity impairment	-24.3 (27.850)	-23.2 (29.861)
Work productivity loss	-31.9 (29.392)	-28.6 (27.996)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Absenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2101
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.97
	Confidence Interval	(2-Sided) 95%; -2.48 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Presenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2971
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.93 to 0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Total activity impairment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5499
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -2.59 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0758
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-1.08
	Confidence Interval	(2-Sided) 95%; -2.28 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in WPAI-PSO Score in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	The WPAI-PSO is a self-administered questionnaire comprised of 6 questions about effects of psoriasis on the patient's ability to work and perform regular activities based on the previous 7 days. The questionnaire quantifies the number of hours the respondent was unable to work and evaluates how much the respondent's psoriasis affected productivity while working. For respondents who were not in paid employment, the questionnaire evaluated how much the respondent's psoriasis affects their ability to perform regular daily activities. Four outcomes were generated from the WPAI-PSO: % Absenteeism: percent work time missed due to health; % Presenteism: percent impairment while working due to health; % Total work productivity impairment: percent overall work impairment due to health; % Total activity impairment: percent activity impairment due to health for all respondents. First 3 outcomes applied to employed participants only. A negative change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and week 52, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	114	92
Absenteeism	-2.36 (12.990)	-3.45 (18.698)
Presenteeism	-22.9 (28.377)	-22.1 (26.333)
Total activity impairment	-23.1 (28.657)	-21.7 (29.905)
Work productivity loss	-18.2 (28.824)	-22.5 (25.192)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Absenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4156
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; -1.71 to 4.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Presenteeism
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8619
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; -6.59 to 7.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Total activity impairment
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6139
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.61
	Confidence Interval	(2-Sided) 95%; -6.31 to 10.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Work productivity loss
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5674
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; -4.16 to 7.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Pain, Itching and Scaling Score in Participants With a PASI 90 Response at Week 24
Description	Self-administered, 11-point numeric rating scales (NRS, 0-10) were used to evaluate the patients' assessment of their current pain, itching and scaling. Respondents answered the following questions for the assessment: Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours?; Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours?; and Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours? Patients had to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the understanding that the 0 represents the absence or null end of the pain, itching, or scale intensity (i.e. no pain, itching or scaling) and the 10 represents the other extreme of pain, itching, or scaling intensity (i.e. pain, itching or scaling as bad as it could be). The number that the patient selected represents his or her intensity score in the respective category. A negative change from baseline indicates improvement
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and week 52, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	644	662
Pain	-4.56 (2.771)	-4.17 (2.2727)
Itching	-5.59 (2.885)	-5.20 (2.985)
Scaling	-6.05 (2.659)	-5.73 (2.757)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1219
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Itching
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Scaling
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Pain, Itching and Scaling Score in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	Self-administered, 11-point numeric rating scales (NRS, 0-10) were used to evaluate the patients' assessment of their current pain, itching and scaling. Respondents answered the following questions for the assessment: Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours?; Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours?; and Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours? Patients had to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the understanding that the 0 represents the absence or null end of the pain, itching, or scale intensity (i.e. no pain, itching or scaling) and the 10 represents the other extreme of pain, itching, or scaling intensity (i.e. pain, itching or scaling as bad as it could be). The number that the patient selected represents his or her intensity score in the respective category. A negative change from baseline indicates improvement
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and week 52, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	114	92
Pain	-3.59 (2.754)	-3.68 (3.049)
Itching	-4.13 (2.883)	-4.49 (3.129)
Scaling	-4.66 (2.960)	-5.40 (2.899)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Pain
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6457
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95%; -0.57 to 0.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Itching
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6136
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.56 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Scaling
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0203
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.12 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Visual Analogue Scale (VAS) in Participants With a PASI 90 Response at Week 24
Description	A visual analogue scale (VAS) was used within the EQ-5D. This scale recorded the respondent's self-rated health on a vertical 20-cm VAS where the endpoints were labeled "best imaginable health state" and "worst imaginable health state." This resulted in a numeric value set ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state"). A positive change from baseline indicates improvement.
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and week 52, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	603	620
Mean (Standard Deviation) [score on a scale]	24.34 (23.296)	21.24 (22.074)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	2.22
	Confidence Interval	(2-Sided) 95%; 0.77 to 3.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change From Baseline in the EQ-5D VAS in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	A visual analogue scale (VAS) was used within the EQ-5D. This scale recorded the respondent's self-rated health on a vertical 20-cm VAS where the endpoints were labeled "best imaginable health state" and "worst imaginable health state." This resulted in a numeric value set ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state").
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and week 52, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	103	88
Mean (Standard Deviation) [score on a scale]	15.86 (20.099)	18.92 (19.855)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2823
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-2.31
	Confidence Interval	(2-Sided) 95%; -6.55 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change From Baseline in the EQ-5D Utility Index (Germany, United Kingdom (UK)) in Participants With a PASI 90 Response at Week 24
Description	The EQ-5D quantifies the health state of a patient for the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort & anxiety/depression. In this study the EQ-5D-5L version has been used which evaluates each of these dimensions using the following 5 labels: no problems, slight problems, moderate problems, severe problems & unable to/extreme problems. Based on the 5 dimensions, a summary score (utility index) was derived using country specific value sets evaluating the patient condition described by the outcome in the single dimensions. The EQ-5D-5L (in this trail) utility index based on the crosswalk value sets available from the EuroQol for Germany & UK (https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/) was calculated. A positive change from baseline indicates improvement. A visual analogue scale was used within the EQ-5D measuring the health state of the patients, ranging from 0 (worst imaginable health state) up to 100 (best imaginable health state).
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Only participants from the FAS-P90R, who had evaluable data at both baseline and week 52, were analyzed. The FAS-P90R included all participants who were rated as PASI 90 responders at the Week 24 visit, randomized to treatment groups 1 or 2 and received at least one dose of study drug at or after visit Week 24.

Arm/Group Title	Treatment Period 2: Group 1	Treatment Period 2: Group 2
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.
Measure Participants	605	623
Germany	0.17 (0.200)	0.13 (0.182)
UK	0.28 (0.250)	0.22 (0.230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Germany
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0861
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.00 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	UK
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0117
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; 0.00 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline in the EQ-5D Utility Index (Germany, UK) in Participants With a PASI Response of ≥75 to <90 at Week 24
Description	The EQ-5D quantifies the health state of a patient for the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. In the current study the EQ-5D-5L version has been used which evaluates each of these dimensions using the following five labels: "no problems", "slight problems", "moderate problems", "severe problems" and "unable to/extreme problems". Based on the five dimensions, a summary score (utility index) was derived using country specific value sets evaluating the patient condition described by the outcome in the single dimensions. For this trial, the EQ-5D-5L utility index based on the crosswalk value sets available from the EuroQol for Germany and for UK (https://euroqol.org/eq-5d-instruments/eq-5d-5l-about/) was calculated. A visual analogue scale (VAS) was used within the EQ-5D measuring the health state of the patients, ranging from 0 (="worst imaginable health state") up to 100 (="best imaginable health state").
Time Frame	Baseline, Week 52

Outcome Measure Data

Analysis Population Description

Participants from the FAS-P75R, who had evaluable data at both baseline and week 52, were analyzed. FAS-P75R: All participants who were rated as PASI 75 responders but did not achieve a PASI 90 response at Week 24, were randomized to treatment groups 3 or 4 and who received at least one dose of study drug at or after Week 24.

Arm/Group Title	Treatment Period 2: Group 3	Treatment Period 2: Group 4
Arm/Group Description	Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.	Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
Measure Participants	103	89
Germany	0.11 (0.164)	0.13 (0.164)
UK	0.18 (0.206)	0.21 (0.204)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	Germany
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1852
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Treatment Period 2: Group 1, Treatment Period 2: Group 2
	Comments	UK
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2203
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LSM estimate
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Week 52
Adverse Event Reporting Description	The Adverse Events (AE) dataset has MedDRA version 19.1 (5345 records) and 20.0 (1272 records).
Arm/Group Title	Treatment Period 1: All Participants		Treatment Period 2: Group 1		Treatment Period 2: Group 2		Treatment Period 2: Group 3		Treatment Period 2: Group 4
Arm/Group Description	Participants received secukinumab 300 mg subcutaneous (s.c.) every 4 weeks for 24 weeks.		Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.		Participants with moderate to severe plaque psoriasis who had reached PASI 90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 6 weeks.		Participants with moderate to severe plaque psoriasis who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks will be treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 4 weeks.		Participants with moderate to severe plaque psoriasis, who had reached PASI 75 to <90 response after 24 weeks of treatment with secukinumab 300 mg s.c. every 4 weeks, were treated with Secukinumab 300 mg s.c. from week 24 until Week 52 every 2 weeks.
All Cause Mortality
	Treatment Period 1: All Participants		Treatment Period 2: Group 1		Treatment Period 2: Group 2		Treatment Period 2: Group 3		Treatment Period 2: Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Serious Adverse Events
	Treatment Period 1: All Participants		Treatment Period 2: Group 1		Treatment Period 2: Group 2		Treatment Period 2: Group 3		Treatment Period 2: Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	73/1647 (4.4%)		25/644 (3.9%)		25/662 (3.8%)		4/114 (3.5%)		3/93 (3.2%)
Cardiac disorders
Acute myocardial infarction	1/1647 (0.1%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Angina pectoris	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Atrial fibrillation	0/1647 (0%)		0/644 (0%)		2/662 (0.3%)		0/114 (0%)		0/93 (0%)
Atrial flutter	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Coronary artery disease	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Coronary artery stenosis	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Myocardial infarction	0/1647 (0%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Myocardial ischaemia	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Ear and labyrinth disorders
Hypoacusis	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Tympanic membrane perforation	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Gastrointestinal disorders
Abdominal pain upper	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Colitis ulcerative	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Crohn's disease	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Gastrointestinal disorder	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Haematochezia	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Haemorrhoids	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Inguinal hernia	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Intestinal polyp	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pancreatitis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
General disorders
Asthenia	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Oedema peripheral	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Hepatobiliary disorders
Alcoholic liver disease	0/1647 (0%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Bile duct stone	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Biliary colic	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Cholecystitis acute	2/1647 (0.1%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Cholelithiasis	1/1647 (0.1%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Hepatic function abnormal	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Hepatotoxicity	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Infections and infestations
Abscess jaw	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Appendicitis	1/1647 (0.1%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Bronchiolitis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Endocarditis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Erysipelas	2/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Gastroenteritis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Giardiasis	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Herpes zoster	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Infectious mononucleosis	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Osteomyelitis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pilonidal cyst	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pneumonia	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Pneumonia bacterial	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pneumonia pseudomonal	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Respiratory tract infection	0/1647 (0%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		1/93 (1.1%)
Staphylococcal bacteraemia	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Tonsillitis	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Urinary tract infection	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Urosepsis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Viral infection	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	2/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Bone contusion	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Clavicle fracture	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Fracture	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Joint dislocation	1/1647 (0.1%)		0/644 (0%)		2/662 (0.3%)		0/114 (0%)		0/93 (0%)
Joint injury	2/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Ligament rupture	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Ligament sprain	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Meniscus injury	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Radius fracture	0/1647 (0%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Spinal column injury	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Subarachnoid haemorrhage	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Tendon rupture	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Thermal burn	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Tibia fracture	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Investigations
Alanine aminotransferase increased	9/1647 (0.5%)		1/644 (0.2%)		1/662 (0.2%)		1/114 (0.9%)		0/93 (0%)
Aspartate aminotransferase increased	10/1647 (0.6%)		2/644 (0.3%)		1/662 (0.2%)		1/114 (0.9%)		0/93 (0%)
Blood bilirubin increased	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Hepatic enzyme increased	3/1647 (0.2%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Liver function test increased	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Transaminases increased	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Metabolism and nutrition disorders
Hypoglycaemia	2/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Bursitis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Intervertebral disc protrusion	3/1647 (0.2%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Osteoarthritis	0/1647 (0%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Basal cell carcinoma	2/1647 (0.1%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Bowen's disease	2/1647 (0.1%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Cholesteatoma	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Gastric cancer stage II	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Lung adenocarcinoma	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Malignant melanoma	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Malignant melanoma in situ	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Oral fibroma	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Plasma cell myeloma	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Skin cancer	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Thyroid adenoma	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Nervous system disorders
Burning sensation	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Cerebral ischaemia	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Cerebrovascular accident	2/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Epilepsy	1/1647 (0.1%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Facial nerve disorder	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Haemorrhagic stroke	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Monoplegia	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Peripheral sensorimotor neuropathy	0/1647 (0%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		1/93 (1.1%)
Seizure	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Tension headache	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Psychiatric disorders
Alcohol abuse	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Anxiety disorder	1/1647 (0.1%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Confusional state	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Depression	2/1647 (0.1%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Schizophrenia	1/1647 (0.1%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Renal and urinary disorders
Calculus urethral	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Renal colic	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Renal failure	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Ureteric stenosis	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Reproductive system and breast disorders
Breast enlargement	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Peyronie's disease	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Prostatitis	0/1647 (0%)		0/644 (0%)		0/662 (0%)		1/114 (0.9%)		0/93 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Nasal polyps	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Pulmonary embolism	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	0/1647 (0%)		1/644 (0.2%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Dermatitis exfoliative	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Lichenoid keratosis	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Skin exfoliation	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Social circumstances
Alcohol use	0/1647 (0%)		0/644 (0%)		1/662 (0.2%)		0/114 (0%)		0/93 (0%)
Vascular disorders
Deep vein thrombosis	0/1647 (0%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		1/93 (1.1%)
Iliac artery occlusion	1/1647 (0.1%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		0/93 (0%)
Other (Not Including Serious) Adverse Events
	Treatment Period 1: All Participants		Treatment Period 2: Group 1		Treatment Period 2: Group 2		Treatment Period 2: Group 3		Treatment Period 2: Group 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	884/1647 (53.7%)		272/644 (42.2%)		288/662 (43.5%)		64/114 (56.1%)		60/93 (64.5%)
Ear and labyrinth disorders
Vertigo	4/1647 (0.2%)		2/644 (0.3%)		2/662 (0.3%)		1/114 (0.9%)		2/93 (2.2%)
Eye disorders
Conjunctivitis allergic	6/1647 (0.4%)		3/644 (0.5%)		0/662 (0%)		1/114 (0.9%)		2/93 (2.2%)
Eye pruritus	5/1647 (0.3%)		0/644 (0%)		0/662 (0%)		0/114 (0%)		3/93 (3.2%)
Gastrointestinal disorders
Diarrhoea	74/1647 (4.5%)		16/644 (2.5%)		22/662 (3.3%)		4/114 (3.5%)		0/93 (0%)
Odynophagia	7/1647 (0.4%)		4/644 (0.6%)		6/662 (0.9%)		1/114 (0.9%)		3/93 (3.2%)
Toothache	34/1647 (2.1%)		11/644 (1.7%)		11/662 (1.7%)		3/114 (2.6%)		1/93 (1.1%)
General disorders
Fatigue	41/1647 (2.5%)		5/644 (0.8%)		2/662 (0.3%)		0/114 (0%)		0/93 (0%)
Injection site haematoma	18/1647 (1.1%)		2/644 (0.3%)		1/662 (0.2%)		0/114 (0%)		2/93 (2.2%)
Pyrexia	36/1647 (2.2%)		10/644 (1.6%)		8/662 (1.2%)		2/114 (1.8%)		1/93 (1.1%)
Infections and infestations
Bronchitis	23/1647 (1.4%)		12/644 (1.9%)		6/662 (0.9%)		1/114 (0.9%)		3/93 (3.2%)
Cystitis	12/1647 (0.7%)		3/644 (0.5%)		3/662 (0.5%)		0/114 (0%)		2/93 (2.2%)
Folliculitis	31/1647 (1.9%)		8/644 (1.2%)		8/662 (1.2%)		1/114 (0.9%)		2/93 (2.2%)
Gastroenteritis	22/1647 (1.3%)		10/644 (1.6%)		10/662 (1.5%)		3/114 (2.6%)		2/93 (2.2%)
Influenza	36/1647 (2.2%)		17/644 (2.6%)		19/662 (2.9%)		4/114 (3.5%)		4/93 (4.3%)
Nasopharyngitis	6/1647 (0.4%)		3/644 (0.5%)		6/662 (0.9%)		0/114 (0%)		2/93 (2.2%)
Oral candidiasis	25/1647 (1.5%)		9/644 (1.4%)		14/662 (2.1%)		0/114 (0%)		3/93 (3.2%)
Oral herpes	41/1647 (2.5%)		12/644 (1.9%)		8/662 (1.2%)		3/114 (2.6%)		0/93 (0%)
Pulpitis dental	4/1647 (0.2%)		1/644 (0.2%)		2/662 (0.3%)		2/114 (1.8%)		2/93 (2.2%)
Rhinitis	52/1647 (3.2%)		8/644 (1.2%)		12/662 (1.8%)		3/114 (2.6%)		0/93 (0%)
Sinusitis	22/1647 (1.3%)		8/644 (1.2%)		6/662 (0.9%)		1/114 (0.9%)		2/93 (2.2%)
Tonsillitis	34/1647 (2.1%)		8/644 (1.2%)		9/662 (1.4%)		2/114 (1.8%)		3/93 (3.2%)
Upper respiratory tract infection	65/1647 (3.9%)		18/644 (2.8%)		16/662 (2.4%)		7/114 (6.1%)		5/93 (5.4%)
Urinary tract infection	26/1647 (1.6%)		16/644 (2.5%)		8/662 (1.2%)		3/114 (2.6%)		3/93 (3.2%)
Viral upper respiratory tract infection	368/1647 (22.3%)		94/644 (14.6%)		95/662 (14.4%)		23/114 (20.2%)		22/93 (23.7%)
Injury, poisoning and procedural complications
Arthropod bite	3/1647 (0.2%)		4/644 (0.6%)		4/662 (0.6%)		0/114 (0%)		2/93 (2.2%)
Investigations
Alanine aminotransferase increased	10/1647 (0.6%)		4/644 (0.6%)		6/662 (0.9%)		2/114 (1.8%)		4/93 (4.3%)
Aspartate aminotransferase increased	8/1647 (0.5%)		4/644 (0.6%)		3/662 (0.5%)		1/114 (0.9%)		3/93 (3.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	50/1647 (3%)		16/644 (2.5%)		19/662 (2.9%)		3/114 (2.6%)		4/93 (4.3%)
Arthritis	4/1647 (0.2%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		2/93 (2.2%)
Back pain	64/1647 (3.9%)		18/644 (2.8%)		28/662 (4.2%)		4/114 (3.5%)		1/93 (1.1%)
Nervous system disorders
Headache	141/1647 (8.6%)		31/644 (4.8%)		27/662 (4.1%)		6/114 (5.3%)		1/93 (1.1%)
Migraine	9/1647 (0.5%)		1/644 (0.2%)		1/662 (0.2%)		0/114 (0%)		2/93 (2.2%)
Respiratory, thoracic and mediastinal disorders
Cough	61/1647 (3.7%)		11/644 (1.7%)		10/662 (1.5%)		3/114 (2.6%)		0/93 (0%)
Oropharyngeal pain	46/1647 (2.8%)		13/644 (2%)		17/662 (2.6%)		3/114 (2.6%)		1/93 (1.1%)
Skin and subcutaneous tissue disorders
Dermatitis atopic	3/1647 (0.2%)		2/644 (0.3%)		1/662 (0.2%)		0/114 (0%)		2/93 (2.2%)
Dermatitis contact	9/1647 (0.5%)		4/644 (0.6%)		1/662 (0.2%)		0/114 (0%)		3/93 (3.2%)
Eczema	20/1647 (1.2%)		8/644 (1.2%)		14/662 (2.1%)		3/114 (2.6%)		1/93 (1.1%)
Erythrodermic psoriasis	0/1647 (0%)		0/644 (0%)		0/662 (0%)		3/114 (2.6%)		1/93 (1.1%)
Pruritus	65/1647 (3.9%)		9/644 (1.4%)		11/662 (1.7%)		2/114 (1.8%)		4/93 (4.3%)
Psoriasis	21/1647 (1.3%)		12/644 (1.9%)		16/662 (2.4%)		11/114 (9.6%)		8/93 (8.6%)
Vascular disorders
Hypertension	55/1647 (3.3%)		7/644 (1.1%)		10/662 (1.5%)		4/114 (3.5%)		4/93 (4.3%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.