NCT01961609: SIGNATURE

Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants.

Completed Phase 3 Results posted Last updated 18 March 2019

What this trial tests

Phase 3 trial testing Secukinumab (AIN457) in Psoriasis in 235 participants. Completed in 12 July 2016.

Timeline

9 October 2013

Primary endpoint
12 July 2016

12 July 2016

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	235
Start date	9 October 2013
Primary completion	12 July 2016
Estimated completion	12 July 2016
Sites	54 locations across United Kingdom, Ireland

Drugs / interventions tested

• Secukinumab (AIN457) — full drug profile →

Conditions studied

• Psoriasis — all drugs for Psoriasis →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Psoriasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 16 Weeks Primary · 16 weeks

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 75 is de

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	65.3

Percentage of Secukinumab 150 mg Participants Achieving PASI 75 at 16 Weeks Secondary · 16 Weeks

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 75 is de

Group	Value	95% CI
Secukinumab (AIN457) 150 mg	44.3

Percentage of Participants Achieving PASI 75 According to 3 Key Participant Subgroups (Primary Inadequate Response (IR), Secondary IR and IR After More Than One Anti-TNFalpha Therapies) at 16 Weeks Secondary · 16 Weeks

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 75 is de

Group	Value	95% CI
Secukinumab (AIN457) 300 mg Subgroup 1	71.4
Secukinumab (AIN457) 300 mg Subgroup 2	70.5
Secukinumab (AIN457) 300 mg Subgroup 3	47.7
Secukinumab (AIN457) 150 mg Subgroup 1	38.9
Secukinumab (AIN457) 150 mg Subgroup 2	61.9
Secukinumab (AIN457) 150 mg Subgroup 3	32.4

Percentage of Participants Achieiving PASI 75 - Initiation Period Secondary · 2 ,4, 8, 12 and 16 Weeks

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 75 is de

Week 2

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	1.7
Secukinumab (AIN457) 150 mg	2.6

Week 4

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	27.1
Secukinumab (AIN457) 150 mg	18.3

Week 8

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	60.2
Secukinumab (AIN457) 150 mg	40.0

Week 12

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	61.9
Secukinumab (AIN457) 150 mg	52.2

Week 16

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	65.3
Secukinumab (AIN457) 150 mg	44.3

Percentage of Participants Achieiving PASI 75 - Maintenance 1 Period Secondary · 16, 24 and 48 Weeks

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 75 is de

Week 16

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	72.0
Secukinumab (AIN457) 150 mg	75.8
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	2.7

Week 24

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	61.7
Secukinumab (AIN457) 150 mg	68.2
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	13.5

Week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	52.3
Secukinumab (AIN457) 150 mg	39.4
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	8.1

Percentage of Participants Achieiving PASI 75 - Maintenance 2 Period Secondary · 48 and 72 Weeks

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 75 is de

Week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	65.1
Secukinumab (AIN457) 150 mg	80.6
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	18.8
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	4.2

Week 72

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	65.1
Secukinumab (AIN457) 150 mg	58.1
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	25.0
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	37.5

Percentage of Participants Achieving PASI 50 and PASI 90 - Initiation Period Secondary · 2, 4, 8, 12, 16 Weeks

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 and P

PASI 50, week 2

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	28.0
Secukinumab (AIN457) 150 mg	25.2

PASI 50, week 4

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	63.6
Secukinumab (AIN457) 150 mg	57.4

PASI 50, week 8

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	84.7
Secukinumab (AIN457) 150 mg	67.8

PASI 50, week 12

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	82.2
Secukinumab (AIN457) 150 mg	69.6

PASI 50, week 16

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	82.2
Secukinumab (AIN457) 150 mg	65.2

PASI 90, week 2

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	0
Secukinumab (AIN457) 150 mg	0

PASI 90, week 4

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	6.8
Secukinumab (AIN457) 150 mg	4.3

PASI 90, week 8

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	25.4
Secukinumab (AIN457) 150 mg	20.0

Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 1 Period Secondary · 16, 24 and 48 Weeks

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 and P

PASI 50, week 16

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	89.7
Secukinumab (AIN457) 150 mg	95.5
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	24.3

PASI 50, week 24

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	80.4
Secukinumab (AIN457) 150 mg	89.4
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	54.1

PASI 50, week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	70.1
Secukinumab (AIN457) 150 mg	65.2
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	32.4

PASI 90, week 16

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	45.8
Secukinumab (AIN457) 150 mg	34.8
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	0

PASI 90, week 24

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	39.3
Secukinumab (AIN457) 150 mg	37.9
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	2.7

PASI 90, week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	31.8
Secukinumab (AIN457) 150 mg	18.2
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	5.4

Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 2 Period Secondary · 48 and 72 Weeks

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 and P

PASI 50, week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	88.0
Secukinumab (AIN457) 150 mg	96.8
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	75.0
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	50.0

PASI 50, week 72

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	74.7
Secukinumab (AIN457) 150 mg	80.6
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	37.5
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	70.8

PASI 90, week 48

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	41.0
Secukinumab (AIN457) 150 mg	38.7
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	12.5
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	0

PASI 90, week 72

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	38.6
Secukinumab (AIN457) 150 mg	22.6
Secukinumab (AIN457) 150 mg - 300 mg (Maintanence Period 1)	18.8
Secukinumab (AIN457) 150 mg - 300 mg (Maintenance Period 2)	16.7

Percentage of Participants Who Have Failed on One Anti-TNFα Achieving PASI 75 (Subgroups 1 and 2 Combined) at 16 Weeks Secondary · 16 Weeks

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 75 is de

Group	Value	95% CI
Secukinumab (AIN457A) 300 mg Subgroups 1 and 2 Combined)	70.7
Secukinumab (AIN457) 150 mg Subgroups 1 and 2	55.0

Percentage of Participants Achieving NICE Continuation Criteria (PASI 75 or PASI 50 Plus a 5 Point Improvement in DLQI) at 16 Weeks Secondary · 16 Weeks

PASI 75 is defined as participants achieving ≥ 75% improvement from baseline. The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases. The measure is widely used: it has been tested across 32 different skin conditions and is available in 55 languages. 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.

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	81.4
Secukinumab (AIN457) 150 mg	60.9

Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Total Scores - Initiation Period Secondary · Baseline, week 12, and week 16

The DLQI is a ten item general dermatology disability index designed to assess health-related quality of life in adult participants with skin diseases. The measure is widely used: it has been tested across 32 different skin conditions and is available in 55 languages. 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

Week 12, initiation

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	-15.6	± 7.49
Secukinumab (AIN457) 150 mg	-13.2	± 7.36

Week 16, initiation

Group	Value	95% CI
Secukinumab (AIN457) 300 mg	-16.1	± 6.80
Secukinumab (AIN457) 150 mg	-12.3	± 7.68

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Secukinumab (AIN457) 150mg

Serious: 14/115 (12%)

Deaths: —

Secukinumab (AIN457) 300mg

Serious: 24/179 (13%)

Deaths: —

Serious adverse events (50 terms)

Reaction	System	Secukinumab (AIN457) 150mg	Secukinumab (AIN457) 300mg
Myocardial infarction	Cardiac disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Diverticulitis	Infections and infestations	—	—
Lower respiratory tract infection	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Psoriasis	Skin and subcutaneous tissue disorders	—	—
Lymphadenopathy	Blood and lymphatic system disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Food poisoning	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Pancreatitis	Gastrointestinal disorders	—	—
Chills	General disorders	—	—
Electrocution	General disorders	—	—
Malaise	General disorders	—	—
Peripheral swelling	General disorders	—	—
Pyrexia	General disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Hepatitis alcoholic	Hepatobiliary disorders	—	—
Cellulitis	Infections and infestations	—	—
H1N1 influenza	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Skin infection	Infections and infestations	—	—

Other adverse events (79 terms — click to expand)

Reaction	System	Secukinumab (AIN457) 150mg	Secukinumab (AIN457) 300mg
Nasopharyngitis	Infections and infestations	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Headache	Nervous system disorders	—	—
Psoriasis	Skin and subcutaneous tissue disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Lower respiratory tract infection	Infections and infestations	—	—
Vomiting	Gastrointestinal disorders	—	—
Sinusitis	Infections and infestations	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Fatigue	General disorders	—	—
Influenza	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Joint swelling	Musculoskeletal and connective tissue disorders	—	—
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Dizziness	Nervous system disorders	—	—
Influenza like illness	General disorders	—	—
Vulvovaginal candidiasis	Infections and infestations	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Conjunctivitis	Infections and infestations	—	—
Ear infection	Infections and infestations	—	—
Oral candidiasis	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Seasonal allergy	Immune system disorders	—	—
Oral herpes	Infections and infestations	—	—
Alanine aminotransferase increased	Investigations	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Lipase increased	Investigations	—	—
Depression	Psychiatric disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Dry eye	Eye disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—

Most-reported serious reactions: Myocardial infarction, Vomiting, Diverticulitis, Lower respiratory tract infection, Pneumonia, Cerebrovascular accident, Psoriasis, Lymphadenopathy.

Data from ClinicalTrials.gov NCT01961609 adverse events section.

Sponsor's own description

This study was designed to prove and quantify the hypothesis that secukinumab is effective, safe and well tolerated in the treatment of moderate to severe chronic plaque-type psoriasis in patients who are inadequate responders to anti-TNFα therapy in a United Kingdom (UK) and Republic of Ireland) specific population.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases.
   Schwartz DM, Bonelli M, Gadina M, O'Shea JJ. · · 2016 · cited 474× · PMID 26633291 · DOI 10.1038/nrrheum.2015.167
2. Cytokines in psoriasis.
   Baliwag J, Barnes DH, Johnston A. · · 2015 · cited 262× · PMID 25585875 · DOI 10.1016/j.cyto.2014.12.014
3. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Do G, et al · · 2017 · cited 106× · PMID 29271481 · DOI 10.1002/14651858.cd011535.pub2
4. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2022 · cited 84× · PMID 35603936 · DOI 10.1002/14651858.cd011535.pub5
5. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Afach S, Doney L, et al · · 2020 · cited 78× · PMID 31917873 · DOI 10.1002/14651858.cd011535.pub3
6. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Guelimi R, Garcia-Doval I, et al · · 2023 · cited 67× · PMID 37436070 · DOI 10.1002/14651858.cd011535.pub6
7. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.
   Sbidian E, Chaimani A, Garcia-Doval I, Doney L, et al · · 2021 · cited 54× · PMID 33871055 · DOI 10.1002/14651858.cd011535.pub4
8. Skin immunity and its dysregulation in psoriasis.
   Lanna C, Mancini M, Gaziano R, Cannizzaro MV, et al · · 2019 · cited 27× · PMID 31416396 · DOI 10.1080/15384101.2019.1653099