A 24-week, Multicenter, proSpective stUdy to Evaluate the... | NCT02394561

Status Module

Description Module

Detailed Description

Biological agents represent the most advanced type of treatment for psoriasis. Secukinumab is a human monoclonal anti IL-17A antibody that binds to human IL-17A and neutralizes its bioactivity by inhibiting IL17A produced by both Th17 cells and those of the innate immune system, thus providing complete anti IL17A blockage. Targeting IL-17A has the potential to reduce autoimmune inflammation while leaving other immune functions undisturbed. While targeting of Th1-promoting or Th17-promoting cytokines affects critical mediators such as IFN-γ, IL-22 and IL-21, selective targeting of IL-17A leaves these Th1/17 activities, as well as certain protective functions of innate cells intact. Furthermore, as a fully human monoclonal antibody, secukinumab should reduce immunogenic risks compared to current or emerging antibody therapies that are not fully human.

Many recent studies have shown that highly selective biologic drugs are not effective in every patient and that variations in the genome can be associated with different clinical responses or side effects to a given drug. The PSORS1 locus on chromosome 6p is generally understood to confer the most risk for psoriasis. A specific allele for this locus, HLA C*06, is present in about 60% of psoriatic patient cases. Data linking secukinumab efficacy to a particular genetic marker are lacking.

Recent research has revealed a marked difference in the proportion of PASI 90 achievers at 12 weeks between Cw6-positive and Cw6-negative patients (85.7% vs 56.5%) treated with ustekinumab (Talamonti M et al. 2013) and a greater efficacy of anti-TNFα drugs in CW6 negative patients (Galli et al. 2013).Unlike anti-IL-12/23 agents, secukinumab inhibits IL-17 produced by both Th17 cells after presentation by antigen presenting cells (in this case Cw6) and cells of the innate immune system whose activation does not require antigen presentation. Providing a drug that is equally effective on both Cw6-negative and Cw6-positive patients would be an important clinical accomplishment and would eliminate the need for costly HLA-Cw6 tests. The choice of a cohort study would therefore seem appropriate for this clinical context.

The purpose of this study was to explore the different efficacy and safety profile of secukinumab 300 mg in patients with moderate to severe chronic plaque-type psoriasis, stratified for the presence of HLA-C*06, whose determination was blinded for patients and investigators. The study was conducted both on anti-TNFα-naïve and anti-TNFα failure patients and also stratified for TNFα - 308 polymorphism, BMI, smoking and metabolic syndrome, among others.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cw6-positive AIN457 300 mg	Experimental	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks	Biological: Secukinumab
Cw6-negative AIN457 300 mg	Experimental	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks	Biological: Secukinumab

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Secukinumab	Biological	Secukinumab was supplied as 150 mg solution in pre-filled syringe for subcutaneous injection	Cw6-negative AIN457 300 mg Cw6-positive AIN457 300 mg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage (%) of Patients Who Reach Psoriasis Area Severity Index (PASI) 90 at 16 Weeks - LOCF Approach (ITT Set)	PASI (Langley et al 2015) combines the assessment of the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease). The PASI was assessed at all visits in CORE and extension phases. PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score compared to baseline are defined as PASI 90 responders.	Baseline up to 16 weeks

Secondary Outcomes

Measure	Description	Time Frame
Percentage (%) of Patients With IGA 0/1, PASI 50, PASI 75, PASI 90, PASI 100 Responders by Visit - LOCF Approach (ITT Set)	IGA mod 2011 scale measures severity of the psoriasis on a five-point scale ranging from 0 (no disease, 'clear') to 4 ('very severe'). PASI 50,75,90,100 represent: patients achieving ≥ 50% improvement (reduction) in PASI score compared to baseline, ≥ 75% improvement (reduction), ≥ 90% improvement (reduction) and PASI 100 response/remission: complete clearing of psoriasis (PASI=0).

Eligibility Module

Facility	Status	City	State	ZIP	Country	Contacts
Novartis Investigative Site		Milan	(MI)	20161	Italy
Novartis Investigative Site

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 22, 2016	Jun 7, 2018

Arm/Group Information

ID	Title	Description
BG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
BG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
BG002	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage (%) of Patients Who Reach Psoriasis Area Severity Index (PASI) 90 at 16 Weeks - LOCF Approach (ITT Set)

PASI (Langley et al 2015) combines the assessment of the severity of lesions and the area affected into a single score with a range of 0 (no disease) to 72 (maximal disease). The PASI was assessed at all visits in CORE and extension phases. PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score compared to baseline are defined as PASI 90 responders.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to 16 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Units	Counts
Participants	OG000184 OG001246

Title

Denominators

Categories

Title	Measurements
	OG00080.4(74.0 to 85.9) OG00181.7(76.3 to 86.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG001						difference	-1.3			2-Sided	95	-8.8	6.2					Non-Inferiority	The difference in percentage of patients achieving PASI 90 response between the Cw6-positive cohort and the Cw6-negative cohort was H0 = Cw6-positive minus Cw6-negative ≥0.12 and HA = Cw6-positive minus Cw6-negative was < 0.12. The percentage of PASI 90 response by cohort as well as the difference between cohort together with 97.5% upper CI was provided using Clopper Pearson CI method.

Secondary

Percentage (%) of Patients With IGA 0/1, PASI 50, PASI 75, PASI 90, PASI 100 Responders by Visit - LOCF Approach (ITT Set)

IGA mod 2011 scale measures severity of the psoriasis on a five-point scale ranging from 0 (no disease, 'clear') to 4 ('very severe'). PASI 50,75,90,100 represent: patients achieving ≥ 50% improvement (reduction) in PASI score compared to baseline, ≥ 75% improvement (reduction), ≥ 90% improvement (reduction) and PASI 100 response/remission: complete clearing of psoriasis (PASI=0).

Number of patients varied across visits

Posted

Number

95% Confidence Interval

percentage of participants

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Secondary

Percent Mean Changes From Baseline in IGA Mod 2011 Between Cohorts at Each Time Point (LOCF) (ITT)

IGA mod 2011 scale measures severity of the psoriasis on a five-point scale ranging from 0 (no disease, 'clear') to 4 ('very severe').

The number of patients across visits varied

Posted

Mean

Standard Deviation

percent change

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Secondary

Median Time to Reach PASI 90 and 75 (ITT)

Time in days to reach PASI scores of 90 and 75.

Posted

Median

Inter-Quartile Range

days

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Secondary

Change From Baseline in the Dermatology Life Quality Index (DLQI) (LOCF) (FAS)

The DLQI total score was calculated by summing the score of each domain resulting in a maximum of 30 and a minimum of 0. The higher the score, the more Quality of Life was impaired. Meaning of DLQI Scores: 0-1 = no effect at all on patient's life, 2-5 = small effect on patient's life, 6-10 = moderate effect on patient's life, 11-20= very large effect on patient's life, 21-30 = extremely large effect on patient's life. It was pre-specified that results would be presented for all patients, not by cohort

Number of patients varied across visits. Both arms were combined because there is no clinical rationale to show a difference between the cohorts. Cw6 status does not have any impact on Quality of Life.

Posted

Mean

Standard Deviation

numbers in a score

Baseline up to approximatly 72 weeks

ID	Title	Description
OG000	All Patients	All patients in the Safety Set.

Units	Counts
Participants	OG000

Secondary

Change From Baseline in Mean Scores of HAD-A and HAD-D (Anxiety and Depression) (LOCF) (FAS)

The Hospital Anxiety and Depression Scale (HADS) is a fourteen-item scale.. Seven of the items relate to anxiety and seven relate to depression. This outcome measure was specifically developed to avoid reliance on aspects of these conditions that are also common somatic symptoms of illness, for example fatigue and insomnia or hypersomnia. Calculations of scores: each of the 14 items was rated on a 4-point scale. All items except 7 and 10 were scored as Yes, definitely = 3, Yes, sometimes = 2, No, not much = 1, to No, not at all = 0. Items 7 and 10 were scored as Yes, definitely = 0 to No, not at all = 3 in the reverse order. The HADS consisted of two sub-scores: the HAD-A (anxiety) and HAD-D (depression); each sub-score ranged from 0 to 21 points; scores ≥11 = presence of anxious or depressive disorders; scores between 8-10 points = borderline abnormal, and scores of ≤7 = disorder was not present. It was pre-specified that results would be presented for all patients, not by cohort

Number of patients varies by visit. Both arms were combined because there is no clinical rationale to show a difference between the cohorts. Cw6 status does not have any impact on anxiety and depression.

Posted

Mean

Standard Deviation

numbers on a scale

Baseline up approximately 72 weeks

ID	Title	Description
OG000	All Patients	All patients in the Safety Set

Units

Secondary

Correlation Between the Hospital Anxiety and Depression Scale (HADS) and PASI (FAS)

PASI score, HADS questionnaire correlation using Spearman rank correlation coefficient. It was pre-specified that results would be presented for all patients, not by cohort

Both arms were combined because there is no clinical rationale to show a difference between the cohorts. Cw6 status does not have any impact on anxiety and depression.

Posted

Number

numbers on scores

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	All Patients	All patients in the Safety Set

Units	Counts
Participants	OG000

Secondary

Changes From Baseline in Body Mass Index (Safety Set)

Change in Body mass index from baseline for patients with a value at baseline and the respective post-baseline visit

Number of patients varied across visits

Posted

Mean

Standard Deviation

kg/m2

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Secondary

Changes From Baseline in Waist Circumference (Safety Set)

Change in waist circumference from baseline for patients with a value at baseline and the respective post-baseline visit

Number of patients varied across visits

Posted

Mean

Standard Deviation

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Secondary

Changes From Baseline in Weight (Safety Set)

Change in weight from baseline for patients with a value at baseline and the respective post-baseline visit

Number of patients varied across visits

Posted

Mean

Standard Deviation

Baseline up to approximately 72 weeks

ID	Title	Description
OG000	Cw6-positive AIN457 300 mg	Stratified to Cw6 positive cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks
OG001	Cw6-negative AIN457 300 mg	Stratified to Cw6 negative cohort. Investigators and patients were blinded to Cw6 results. All patients were treated according to an induction regimen of two injections of secukinumab 150 mg a week for five weeks starting at baseline (week 0), followed by a maintenance period of two injections per month. At week 16, patients achieving PASI 50 response were eligible to continue on secukinumab for an additional 8 weeks in CORE. Eligible patients with at least a PASI 75 response were included in the extension phase, up to 72 weeks

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Cardiac arrest	Cardiac disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Asthenia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Non-cardiac chest pain	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Pyrexia	General disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Hepatic lesion	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Hyperbilirubinaemia	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0003 affected246 at risk EG0010 affected185 at risk
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Gastroenteritis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Perirectal abscess	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Urinary tract infection	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Vulvovaginal candidiasis	Infections and infestations	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Alanine aminotransferase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0002 affected246 at risk EG0010 affected185 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0002 affected246 at risk EG0011 affected185 at risk
Blood bilirubin increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0002 affected246 at risk EG0011 affected185 at risk
Lipase increased	Investigations	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Enthesopathy	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Meniscal degeneration	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Psoriatic arthropathy	Musculoskeletal and connective tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Depression	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Major depression	Psychiatric disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Proteinuria	Renal and urinary disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Scrotal inflammation	Reproductive system and breast disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Laryngeal oedema	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0001 affected246 at risk EG0010 affected185 at risk
Respiratory tract irritation	Respiratory, thoracic and mediastinal disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk
Hyperhidrosis	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment	EG0000 affected246 at risk EG0011 affected185 at risk

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cw6-Negative AIN457 300 mg	Cw6-Negative AIN457 300 mg	2	246	21	246	14	246
EG001	Cw6-Positive AIN457 300 mg	Cw6-Positive AIN457 300 mg	0	185	10	185	20	185

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (20.0)	Systematic Assessment		EG0004 affected246 at risk EG00112 affected185 at risk
Hypertension	Vascular disorders	MedDRA (20.0)	Systematic Assessment		EG00010 affected246 at risk EG00111 affected185 at risk