AIN457 Regimen Finding Extension Study in Participants With Moderate to Severe Psoriasis

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01132612
• Collaborator: (none)
• Enrollment: 275
• Locations: 57
• Arms: 3
• Actual Duration (Months): 77.3
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study was to provide long term clinical data for the compound for the treatment of the indication of moderate to severe chronic plaque-type psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Plaque-type Psoriasis	Drug: AIN457; Drug: Placebo	Phase 2

Detailed Description

In the Proof-of-Concept study (CAIN457A2102/ NCT00669916), AIN457 was proven to be efficacious in the treatment of moderate to severe chronic plaque-type psoriasis. As a result, a phase IIb regimen finding study had been started (CAIN457A2211/NCT00941031).

The data gathered in this extension study of the core study (CAIN457A2211)was used to expand the safety database of the compound for the treatment of moderate to severe chronic plaque-type psoriasis. The participants in the extension study continued to stay on the exact same treatment regimen they were taking when completing the core study. The extension trial was first designed to provide long-term safety data of up to 100 weeks of treatment (32 weeks in the core study plus 68 weeks in the extension study (part 1)), and an additional 12 weeks of treatment-free follow-up for participants who did not continue in the extension study. Amendment 2 provided an additional 156 weeks of treatment (32 weeks in the core study plus 224 weeks in the extension study, equaling 256 weeks of total treatment (part 2)), before participants entered the 12 weeks of treatment-free follow-up. Protocol Amendment 3 extended the prolongation part of the study by up to 104 additional weeks of treatment (part 3) or until the drug was commercially available in the market of the country of participation, whichever occurred first.

Study Design

• Study Type: Interventional
• Actual Enrollment: 275 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter Extension Trial of Subcutaneously Administered AIN457 in Participants With Moderate to Severe Chronic Plaque-type Psoriasis
• Actual Study Start Date: May 11, 2010
• Actual Primary Completion Date: Oct 18, 2016
• Actual Study Completion Date: Oct 18, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fixed-time interval regimen Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Drug: AIN457; AIN457A 150 mg powder for solution; Drug: Placebo; Placebo to AIN457A 150 mg powder for solution
Experimental: Treatment at start of relapse regimen Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Drug: AIN457; AIN457A 150 mg powder for solution; Drug: Placebo; Placebo to AIN457A 150 mg powder for solution
Experimental: Open-label Secukinumab 150 mg sc administered every 4 weeks	Drug: AIN457; AIN457A 150 mg powder for solution

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events, Serious Adverse Events and Deaths [up to week 351]

   Safety was assessed by frequency of adverse events including serious adverse events.

Secondary Outcome Measures

1. Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response [Extension weeks: 1, 25, 73 and 301 (too few data points were available to perform analysis at week 301)]

   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). The IGA 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, 4 = severe and 5 = very severe.

2. Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial [up to week 351]

   Describes the number of participants tested positive for anti-secukinumab antibodies. It refers to the number of participants who had no positive values at baseline but developed them only after start of secukinumab treatment.

Eligibility Criteria

Criteria

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

Key Inclusion Criteria:

• Patients who completed the core study CAIN457A2211. A patient is defined as having completed the core study if he/she completed the study up to and including visit 13 (F4) of the core study

• Patients must be able to understand and communicate with the investigator and comply with the requirement of the study and must given written, signed and dated informed consent before any study assessment is performed.

• Patients must be expected to benefit from the ongoing treatment with AIN457, as assessed by the patient and investigator

• Male patients must consent to practice reliable contraception during the study and for 16 weeks after the last dose of study drug administration Note: Due to new data available from the toxicology studies, the need for male contraception was removed.

Key Exclusion Criteria:

• Patients who experience a second consecutive full relapse at visit 13 ( week F4) of the core study CAIN457A2211

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

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unwilling to use effective contraception during the study and for 16 weeks after stopping treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35233
2	Novartis Investigative Site	Little Rock	Arkansas	United States	72205
3	Novartis Investigative Site	Pasadena	California	United States	91105
4	Novartis Investigative Site	San Diego	California	United States	92123
5	Novartis Investigative Site	Newnan	Georgia	United States	30263
6	Novartis Investigative Site	Snellville	Georgia	United States	30078
7	Novartis Investigative Site	Champaign	Illinois	United States	61820
8	Novartis Investigative Site	Springfield	Illinois	United States	62703
9	Novartis Investigative Site	Evansville	Indiana	United States	47713
10	Novartis Investigative Site	Topeka	Kansas	United States	66606
11	Novartis Investigative Site	Louisville	Kentucky	United States	40291
12	Novartis Investigative Site	Clinton Township	Michigan	United States	48038
13	Novartis Investigative Site	Detroit	Michigan	United States	48202
14	Novartis Investigative Site	Minneapolis	Minnesota	United States	55455
15	Novartis Investigative Site	Saint Louis	Missouri	United States	63117
16	Novartis Investigative Site	Omaha	Nebraska	United States	68131
17	Novartis Investigative Site	Omaha	Nebraska	United States	68144
18	Novartis Investigative Site	Henderson	Nevada	United States	89052
19	Novartis Investigative Site	Rochester	New York	United States	14623
20	Novartis Investigative Site	High Point	North Carolina	United States	27262
21	Novartis Investigative Site	Lake Oswego	Oregon	United States	97035
22	Novartis Investigative Site	Portland	Oregon	United States	97210
23	Novartis Investigative Site	Austin	Texas	United States	78759
24	Novartis Investigative Site	Dallas	Texas	United States	75204
25	Novartis Investigative Site	Charlottesville	Virginia	United States	22911
26	Novartis Investigative Site	Nice		France	06202
27	Novartis Investigative Site	Toulouse Cedex		France	31400
28	Novartis Investigative Site	Berlin		Germany	10117
29	Novartis Investigative Site	Bonn		Germany	53105
30	Novartis Investigative Site	Dresden		Germany	01307
31	Novartis Investigative Site	Erlangen		Germany	91054
32	Novartis Investigative Site	Frankfurt		Germany	60590
33	Novartis Investigative Site	Gottingen		Germany	37075
34	Novartis Investigative Site	Hamburg		Germany	20354
35	Novartis Investigative Site	Hannover		Germany	30625
36	Novartis Investigative Site	Kiel		Germany	24105
37	Novartis Investigative Site	Luebeck		Germany	23538
38	Novartis Investigative Site	Mainz		Germany	55131
39	Novartis Investigative Site	Muenster		Germany	48149
40	Novartis Investigative Site	Tuebingen		Germany	72076
41	Novartis Investigative Site	Kopavogur		Iceland	201
42	Novartis Investigative Site	Afula		Israel	1834111
43	Novartis Investigative Site	Petach Tikva		Israel	49100
44	Novartis Investigative Site	Ramat Gan		Israel	5265601
45	Novartis Investigative Site	Nagoya-city	Aichi	Japan	467-8602
46	Novartis Investigative Site	Fukuoka-city	Fukuoka	Japan	814-0180
47	Novartis Investigative Site	Kitakyushu-city	Fukuoka	Japan	807-8556
48	Novartis Investigative Site	Kurume city	Fukuoka	Japan	830-0011
49	Novartis Investigative Site	Maebashi-city	Gunma	Japan	371-8511
50	Novartis Investigative Site	Chitose	Hokkaido	Japan	066-0021
51	Novartis Investigative Site	Bunkyo-ku	Tokyo	Japan	113-8655
52	Novartis Investigative Site	Itabashi-ku	Tokyo	Japan	173-8610
53	Novartis Investigative Site	Minato-ku	Tokyo	Japan	105-8471
54	Novartis Investigative Site	Shinagawa-ku	Tokyo	Japan	141 8625
55	Novartis Investigative Site	Bergen		Norway	NO-5021
56	Novartis Investigative Site	Oslo		Norway	0424
57	Novartis Investigative Site	Ålesund		Norway	6017

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01132612
• Other Study ID Numbers: CAIN457A2211E1; 2009-017234-51
• First Posted: May 28, 2010
• Last Update Posted: Jan 4, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Novartis Pharmaceuticals: Chronic plaque-type psoriasis; AIN457; dermatology; Moderate to severe chronic plaque-type psoriasis
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Pre-assignment Detail	Participants continued their regimens as assigned in CAIN457A2211 (NCT00941031) and were enrolled into one of the following: fixed time interval regimen (FI), treatment at start of relapse regimen (SR) or open-label (OL). There were no more placebo treated patients at the end of the core. Therefore, there is no placebo arm in the extension.

Arm/Group Title	Fixed-time Interval Regimen	Treatment at Start of Relapse Regimen	Open-label
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Secukinumab 150 mg sc administered every 4 weeks.
Period Title: Overall Study
STARTED	46	42	187
COMPLETED	6	7	17
NOT COMPLETED	40	35	170

Baseline Characteristics

Arm/Group Title	Fixed-time Interval Regimen	Treatment at Start of Relapse Regimen	Open-label	Total
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Secukinumab 150 mg sc administered every 4 weeks.	Total of all reporting groups
Overall Participants	46	42	187	275
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	43.0 (13.71)	39.9 (12.12)	45.0 (11.78)	43.9 (12.27)
Sex: Female, Male (Count of Participants)
Female	15 32.6%	12 28.6%	39 20.9%	66 24%
Male	31 67.4%	30 71.4%	148 79.1%	209 76%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events, Serious Adverse Events and Deaths
Description	Safety was assessed by frequency of adverse events including serious adverse events.
Time Frame	up to week 351

Outcome Measure Data

Analysis Population Description

Extension safety set: the extension safety set consisted of all participants who received at least one dose of study drug during the extension and had at least one post-baseline safety assessment during the extension.

Arm/Group Title	Fixed-time Interval Regimen	Treatment at Start of Relapse Regimen	Open-label
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Secukinumab 150 mg sc administered every 4 weeks.
Measure Participants	46	42	187
Adverse events	44 95.7%	41 97.6%	180 96.3%
Serious adverse events	9 19.6%	4 9.5%	43 23%
Deaths	0 0%	0 0%	1 0.5%

2. Secondary Outcome

Title	Number of Participants With at Least 50%, 75% or 90% Improvement From Baseline in Psoriasis Area and Severity Index (PASI) and IGA Mod 2009 0 or 1 Response
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). The IGA 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, 4 = severe and 5 = very severe.
Time Frame	Extension weeks: 1, 25, 73 and 301 (too few data points were available to perform analysis at week 301)

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS): The FAS, which included all participants who entered the extension and to whom study drug was assigned, was considered for the analysis. Only those participants, who had evaluable data at a given time point, were analyzed at that time point.

Arm/Group Title	Fixed-time Interval Regimen	Treatment at Start of Relapse Regimen	Open-label
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Secukinumab 150 mg sc administered every 4 weeks.
Measure Participants	46	42	187
Extension week 1, PASI 50	43 93.5%	34 81%	163 87.2%
Extension week 1, PASI 75	31 67.4%	16 38.1%	102 54.5%
Extension week 1, PASI 90	17 37%	3 7.1%	61 32.6%
Ext. week 1, IGA mod 2009 0 or 1	24 52.2%	7 16.7%	70 37.4%
Extension week 25, PASI 50	29 63%	27 64.3%	142 75.9%
Extension week 25, PASI 75	19 41.3%	10 23.8%	91 48.7%
Extension week 25, PASI 90	12 26.1%	2 4.8%	42 22.5%
Ext. week 25, IGA mod 2009 0 or 1	15 32.6%	4 9.5%	48 25.7%
Extension week 73, PASI 50	18 39.1%	17 40.5%	100 53.5%
Extension week 73, PASI 75	14 30.4%	8 19%	66 35.3%
Extension week 73, PASI 90	8 17.4%	1 2.4%	31 16.6%
Ext. week 73, IGA mod 2009	9 19.6%	4 9.5%	35 18.7%
Extension week 301, PASI 50	3 6.5%
Extension week 301, PASI 75	2 4.3%
Extension week 301, PASI 90	1 2.2%
Extension week 301, IGA mod 2009	1 2.2%

3. Secondary Outcome

Title	Long-term Immunogenicity Assessed by the Number of Participants Developing Anti Secukinumab Antibodies During the Trial
Description	Describes the number of participants tested positive for anti-secukinumab antibodies. It refers to the number of participants who had no positive values at baseline but developed them only after start of secukinumab treatment.
Time Frame	up to week 351

Outcome Measure Data

Analysis Population Description

Extension safety set: the extension safety set consisted of all participants who received at least one dose of study drug during the extension and had at least one post-baseline safety assessment during the extension.

Arm/Group Title	Fixed-time Interval Regimen	Treatment at Start of Relapse Regimen	Open-label
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter	Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks	Secukinumab 150 mg sc administered every 4 weeks.
Measure Participants	46	41	184
Count of Participants [Participants]	0 0%	0 0%	1 0.5%

Adverse Events

Time Frame	Adverse events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All adverse events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit.
Arm/Group Title	Fixed-time Interval Regimen		Treatment at Start of Relapse Regimen		Open-label
Arm/Group Description	Secukinumab 150 mg subcutaneous (sc) administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter		Placebo administered at Week 1 (baseline) of the extension study and every 12 weeks thereafter. If relapse, then switch to secukinumab 150 mg sc administered every 4 weeks		Secukinumab 150 mg sc administered every 4 weeks.
All Cause Mortality
	Fixed-time Interval Regimen		Treatment at Start of Relapse Regimen		Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fixed-time Interval Regimen		Treatment at Start of Relapse Regimen		Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/46 (19.6%)		4/42 (9.5%)		43/187 (23%)
Cardiac disorders
Acute myocardial infarction	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Angina pectoris	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Arrhythmia	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Cardiac arrest	0/46 (0%)		0/42 (0%)		2/187 (1.1%)
Coronary artery disease	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Coronary artery stenosis	0/46 (0%)		1/42 (2.4%)		0/187 (0%)
Ventricular fibrillation	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Ventricular tachycardia	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Ear and labyrinth disorders
Tinnitus	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Eye disorders
Cataract	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Gastrointestinal disorders
Crohn's disease	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Haemorrhoids	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Inguinal hernia	0/46 (0%)		1/42 (2.4%)		1/187 (0.5%)
Intestinal ischaemia	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Intussusception	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Nausea	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
General disorders
Chest discomfort	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Non-cardiac chest pain	0/46 (0%)		1/42 (2.4%)		1/187 (0.5%)
Hepatobiliary disorders
Hepatic cirrhosis	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Infections and infestations
Abscess bacterial	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Anal abscess	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Campylobacter gastroenteritis	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Cellulitis	0/46 (0%)		1/42 (2.4%)		4/187 (2.1%)
Diverticulitis	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Enterocolitis infectious	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Impetigo	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Infected dermal cyst	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Nail infection	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Osteomyelitis	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Osteomyelitis chronic	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Paronychia	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Staphylococcal abscess	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Staphylococcal infection	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Streptococcal infection	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Urinary tract infection	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Injury, poisoning and procedural complications
Laceration	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Meniscus injury	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Muscle injury	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Road traffic accident	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Tendon injury	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Upper limb fracture	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Investigations
Fibrin D dimer increased	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Streptococcus test positive	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Metabolism and nutrition disorders
Dehydration	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Diabetes mellitus	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Diabetic ketoacidosis	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Hyperkalaemia	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Musculoskeletal and connective tissue disorders
Back pain	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Intervertebral disc disorder	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Intervertebral disc protrusion	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Osteoarthritis	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Tenosynovitis	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/46 (0%)		0/42 (0%)		2/187 (1.1%)
Colon adenoma	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Colon cancer	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Malignant melanoma	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Pleomorphic adenoma	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Superficial spreading melanoma stage unspecified	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Nervous system disorders
Dizziness	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Facial paralysis	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Hemiparesis	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Hepatic encephalopathy	1/46 (2.2%)		0/42 (0%)		0/187 (0%)
Migraine	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Syncope	1/46 (2.2%)		0/42 (0%)		1/187 (0.5%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Psychiatric disorders
Anxiety	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Depression	0/46 (0%)		0/42 (0%)		2/187 (1.1%)
Renal and urinary disorders
Acute kidney injury	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Bladder stenosis	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
End stage renal disease	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Haematuria	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Asthma	1/46 (2.2%)		0/42 (0%)		1/187 (0.5%)
Sleep apnoea syndrome	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Skin and subcutaneous tissue disorders
Dermatitis allergic	0/46 (0%)		0/42 (0%)		1/187 (0.5%)
Psoriasis	0/46 (0%)		0/42 (0%)		2/187 (1.1%)
Other (Not Including Serious) Adverse Events
	Fixed-time Interval Regimen		Treatment at Start of Relapse Regimen		Open-label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/46 (91.3%)		35/42 (83.3%)		164/187 (87.7%)
Gastrointestinal disorders
Abdominal pain upper	2/46 (4.3%)		0/42 (0%)		11/187 (5.9%)
Dental caries	3/46 (6.5%)		1/42 (2.4%)		6/187 (3.2%)
Diarrhoea	2/46 (4.3%)		2/42 (4.8%)		20/187 (10.7%)
Nausea	3/46 (6.5%)		3/42 (7.1%)		12/187 (6.4%)
Toothache	4/46 (8.7%)		1/42 (2.4%)		14/187 (7.5%)
Vomiting	1/46 (2.2%)		3/42 (7.1%)		13/187 (7%)
General disorders
Fatigue	2/46 (4.3%)		3/42 (7.1%)		12/187 (6.4%)
Influenza like illness	1/46 (2.2%)		2/42 (4.8%)		12/187 (6.4%)
Pyrexia	1/46 (2.2%)		4/42 (9.5%)		9/187 (4.8%)
Infections and infestations
Bronchitis	2/46 (4.3%)		1/42 (2.4%)		21/187 (11.2%)
Conjunctivitis	4/46 (8.7%)		0/42 (0%)		4/187 (2.1%)
Gastroenteritis viral	1/46 (2.2%)		4/42 (9.5%)		9/187 (4.8%)
Influenza	4/46 (8.7%)		2/42 (4.8%)		14/187 (7.5%)
Nasopharyngitis	20/46 (43.5%)		16/42 (38.1%)		91/187 (48.7%)
Oral herpes	1/46 (2.2%)		1/42 (2.4%)		10/187 (5.3%)
Pharyngitis streptococcal	3/46 (6.5%)		2/42 (4.8%)		4/187 (2.1%)
Sinusitis	9/46 (19.6%)		3/42 (7.1%)		17/187 (9.1%)
Tonsillitis	1/46 (2.2%)		0/42 (0%)		14/187 (7.5%)
Upper respiratory tract infection	3/46 (6.5%)		4/42 (9.5%)		28/187 (15%)
Urinary tract infection	3/46 (6.5%)		4/42 (9.5%)		6/187 (3.2%)
Injury, poisoning and procedural complications
Contusion	2/46 (4.3%)		2/42 (4.8%)		10/187 (5.3%)
Ligament sprain	1/46 (2.2%)		2/42 (4.8%)		10/187 (5.3%)
Procedural pain	4/46 (8.7%)		0/42 (0%)		6/187 (3.2%)
Investigations
Alanine aminotransferase increased	1/46 (2.2%)		0/42 (0%)		12/187 (6.4%)
C-reactive protein increased	3/46 (6.5%)		0/42 (0%)		6/187 (3.2%)
Metabolism and nutrition disorders
Hypercholesterolaemia	1/46 (2.2%)		3/42 (7.1%)		14/187 (7.5%)
Hypertriglyceridaemia	0/46 (0%)		1/42 (2.4%)		10/187 (5.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/46 (19.6%)		6/42 (14.3%)		43/187 (23%)
Arthritis	3/46 (6.5%)		1/42 (2.4%)		6/187 (3.2%)
Back pain	5/46 (10.9%)		7/42 (16.7%)		30/187 (16%)
Musculoskeletal pain	5/46 (10.9%)		0/42 (0%)		15/187 (8%)
Myalgia	2/46 (4.3%)		3/42 (7.1%)		8/187 (4.3%)
Neck pain	3/46 (6.5%)		1/42 (2.4%)		6/187 (3.2%)
Pain in extremity	4/46 (8.7%)		1/42 (2.4%)		11/187 (5.9%)
Nervous system disorders
Dizziness	3/46 (6.5%)		0/42 (0%)		4/187 (2.1%)
Headache	11/46 (23.9%)		6/42 (14.3%)		29/187 (15.5%)
Psychiatric disorders
Anxiety	0/46 (0%)		0/42 (0%)		11/187 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	2/46 (4.3%)		4/42 (9.5%)		20/187 (10.7%)
Oropharyngeal pain	5/46 (10.9%)		3/42 (7.1%)		14/187 (7.5%)
Skin and subcutaneous tissue disorders
Eczema	4/46 (8.7%)		0/42 (0%)		6/187 (3.2%)
Psoriasis	13/46 (28.3%)		16/42 (38.1%)		59/187 (31.6%)
Vascular disorders
Hypertension	4/46 (8.7%)		6/42 (14.3%)		26/187 (13.9%)

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.