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

Psoriasis Clinical Trial

— SIGNATURE  

Official title:

Secukinumab In Patients With Moderate to Severe Active, Chronic Plaque Psoriasis Who Have Failed on TNFα antaGoNists: A Clinical Trial EvalUating Treatment REsults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01961609
• Other study ID #: CAIN457AGB01
• Status: Completed
• Phase: Phase 3
• Start date: October 9, 2013
• Est. completion date: July 12, 2016

Study information

• Verified date: December 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

There is no clear evidence or guidelines on appropriate treatment once a patient with moderate/severe psoriasis has failed to respond to anti-TNFα therapy, whether a single anti-TNFα therapy failure or multiple anti-TNFα therapy failures.

Numerous double-blind, double-dummy, randomised, parallel-group, active and placebo controlled studies have already been designed and run for the Phase III secukinumab clinical development program, in accordance with Health Authorities guidelines and feedback, including Food and Drug Administration (FDA) and European Medicines Agency (EMA). None of these specifically studied patients who have failed to respond to anti-TNFα therapy as defined by National Institute for Health and Care Excellence (NICE) guidelines.

Therefore, this study utilises a pragmatic, open-label, non-comparator design, which has been shown to be appropriate in similar studies looking at anti-TNFα therapy in patients failing on other therapies (Papp et al. 2012; Strober et al. 2011), to answer the question of whether secukinumab is an appropriate choice in patients who have failed to respond to anti-TNFα therapy (TNF-IR) per NICE definitions, whether a single anti-TNFα therapy failure or multiple anti-TNFα therapy failures.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 235
• Est. completion date: July 12, 2016
• Est. primary completion date: July 12, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Written informed consent must be obtained before any assessment is performed

2. Aged at least 18 years at screening

3. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to screening

4. Moderate to severe disease severity:

• PASI =10 and

• DLQI >10

5. Failed to respond to systemic therapies including cyclosporine and/or methotrexate and/or PUVA (or is intolerant and/or has a contraindication to these)

6. Previously treated with at least one anti-TNFa for moderate or severe psoriasis but is a primary or secondary non-responder

7. Able to communicate well with the investigator, to understand and comply with the requirements of the study.

Key Exclusion Criteria:

1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis)

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

3. Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids (CS), UV therapy). Washout periods detailed in the protocol must be adhered to.

4. 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 on a stable dose for at least four weeks before initiation of study drug.

5. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or the IL-17 receptor

6. 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 hCG laboratory test (> 5 mIU/mL)

7. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they use 2 (two) effective forms of contraception during the study and for 16 weeks after stopping treatment.

8. Men with a female partner of child bearing potential defined as all women physiologically capable of becoming pregnant unless they use 1 (one) effective form of contraception during the study and for 16 weeks after stopping treatment.

9. Active systemic infections during the last two weeks (exception: common cold) prior to initiation of study drug and any infections that reoccur on a regular basis; investigator discretion should be used regarding patients who have travelled or recently resided in areas of endemic mycoses, such as histoplasmosis, coccidioidomycosis or blastomycosis and for patients with underlying conditions that may predispose them to infection, such as advanced or poorly controlled diabetes

10. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection as defined by a positive QuantiFERON TB-Gold test (QFT) at screening. Patients with a positive QFT test may participate in the study if further work up establishes conclusively that the patient has no evidence of active tuberculosis. If presence of latent tuberculosis is established, then treatment must have been initiated and maintained according to UK guidelines.

11. Known infection with HIV, hepatitis B or hepatitis C at screening or at initiation of study drug.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Biological:
• Secukinumab (AIN457)
Secukinumab was supplied in 150mg pre-filled syringes.

Locations

Country	Name	City	State
Ireland	Novartis Investigative Site	Cork
Ireland	Novartis Investigative Site	Dublin
Ireland	Novartis Investigative Site	Dublin 4
United Kingdom	Novartis Investigative Site	Aberdeen	Scotland
United Kingdom	Novartis Investigative Site	Airdrie
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Belfast
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Canterbury	Kent
United Kingdom	Novartis Investigative Site	Cardiff	South Glamorgan
United Kingdom	Novartis Investigative Site	Chester
United Kingdom	Novartis Investigative Site	Cliftonville	Northampton
United Kingdom	Novartis Investigative Site	Coventry	Warwickshire
United Kingdom	Novartis Investigative Site	Dafen	Llanelli
United Kingdom	Novartis Investigative Site	Dudley	West Midlands
United Kingdom	Novartis Investigative Site	Durham
United Kingdom	Novartis Investigative Site	Fife
United Kingdom	Novartis Investigative Site	Frimley	Surrey
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Harlow	Essex
United Kingdom	Novartis Investigative Site	Hull
United Kingdom	Novartis Investigative Site	Ipswich	Suffolk
United Kingdom	Novartis Investigative Site	Lancaster
United Kingdom	Novartis Investigative Site	Leeds	West Yorkshire
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	Liverpool
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London	England
United Kingdom	Novartis Investigative Site	London	GBR
United Kingdom	Novartis Investigative Site	Middlesborough
United Kingdom	Novartis Investigative Site	Middlesex
United Kingdom	Novartis Investigative Site	Newcastle upon Tyne
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Nottingham
United Kingdom	Novartis Investigative Site	Nottingham	Nottinghamshire
United Kingdom	Novartis Investigative Site	Oxford
United Kingdom	Novartis Investigative Site	Plymouth	Devon
United Kingdom	Novartis Investigative Site	Poole
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Rhyl	Wales
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Scaroborough
United Kingdom	Novartis Investigative Site	Scunthorpe
United Kingdom	Novartis Investigative Site	Staffordshire
United Kingdom	Novartis Investigative Site	Stoke-on-Trent
United Kingdom	Novartis Investigative Site	Surrey
United Kingdom	Novartis Investigative Site	Surrey
United Kingdom	Novartis Investigative Site	Wrexham
United Kingdom	Novartis Investigative Site	Yeovil	Somerset
United Kingdom	Novartis Investigative Site	York

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Ireland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 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 defined as participants achieving = 75% improvement from baseline.	16 weeks
Secondary	Percentage of Secukinumab 150 mg Participants Achieving PASI 75 at 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 defined as participants achieving = 75% improvement from baseline.	16 Weeks
Secondary	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	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 defined as participants achieving = 75% improvement from baseline.	16 Weeks
Secondary	Percentage of Participants Achieiving PASI 75 - Initiation Period	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 defined as participants achieving = 75% improvement from baseline.	2 ,4, 8, 12 and 16 Weeks
Secondary	Percentage of Participants Achieiving PASI 75 - Maintenance 1 Period	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 defined as participants achieving = 75% improvement from baseline.	16, 24 and 48 Weeks
Secondary	Percentage of Participants Achieiving PASI 75 - Maintenance 2 Period	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 defined as participants achieving = 75% improvement from baseline.	48 and 72 Weeks
Secondary	Percentage of Participants Achieving PASI 50 and PASI 90 - Initiation Period	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 PASI 90 are defined as participants achieving = 50% and = 90% improvement from baseline, respectively.	2, 4, 8, 12, 16 Weeks
Secondary	Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 1 Period	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 PASI 90 are defined as participants achieving = 50% and = 90% improvement from baseline, respectively.	16, 24 and 48 Weeks
Secondary	Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 2 Period	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 PASI 90 are defined as participants achieving = 50% and = 90% improvement from baseline, respectively.	48 and 72 Weeks
Secondary	Percentage of Participants Who Have Failed on One Anti-TNFa Achieving PASI 75 (Subgroups 1 and 2 Combined) at 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 defined as participants achieving = 75% improvement from baseline.	16 Weeks
Secondary	Percentage of Participants Achieving NICE Continuation Criteria (PASI 75 or PASI 50 Plus a 5 Point Improvement in DLQI) at 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.	16 Weeks
Secondary	Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Total Scores - Initiation Period	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 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 change from baseline indicates improvement.	Baseline, week 12, and week 16
Secondary	Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 1 Period	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 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 change from baseline indicates improvement.	Baseline, 16, 24 and 48 weeks
Secondary	Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 2 Period	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 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 change from baseline indicates improvement.	Baseline, 48 and 72 weeks
Secondary	Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Initiation Period	The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score.	Baseline, 12 and 16 weeks
Secondary	Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 1 Period	The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score.	Baseline, 16, 24 and 48 weeks
Secondary	Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 2 Period	The EQ-5D is an instrument used to assess a participant's health status. The instrument includes a descriptive profile and a visual analog scale (VAS). The descriptive profile includes 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension had 3 response levels: no problems, some problems and severe problems. The VAS is a vertical scale that assesses the health status from 0 (worst possible health state) to 100 (best possible health state). This outcome measures the percent change in VAS score.	Baseline, 48 and 72 weeks