Clinical trial NCT01961609: Secukinumab in Tumor Necrosis Factor (TNF) - Inadequate Response (IR) Psoriasis Participants.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Keywords: Chronic plaque psoriasis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-10-11
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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-TNFα 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.

Primary outcomes:
measure: Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 16 Weeks
timeFrame: 16 weeks
Secondary outcomes:
measure: Percentage of Secukinumab 150 mg Participants Achieving PASI 75 at 16 Weeks
timeFrame: 16 Weeks
measure: 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
timeFrame: 16 Weeks
measure: Percentage of Participants Achieiving PASI 75 - Initiation Period
timeFrame: 2 ,4, 8, 12 and 16 Weeks
measure: Percentage of Participants Achieiving PASI 75 - Maintenance 1 Period
timeFrame: 16, 24 and 48 Weeks
measure: Percentage of Participants Achieiving PASI 75 - Maintenance 2 Period
timeFrame: 48 and 72 Weeks
measure: Percentage of Participants Achieving PASI 50 and PASI 90 - Initiation Period
timeFrame: 2, 4, 8, 12, 16 Weeks
measure: Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 1 Period
timeFrame: 16, 24 and 48 Weeks
measure: Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 2 Period
timeFrame: 48 and 72 Weeks
measure: Percentage of Participants Who Have Failed on One Anti-TNFα Achieving PASI 75 (Subgroups 1 and 2 Combined) at 16 Weeks
timeFrame: 16 Weeks
measure: Percentage of Participants Achieving NICE Continuation Criteria (PASI 75 or PASI 50 Plus a 5 Point Improvement in DLQI) at 16 Weeks
timeFrame: 16 Weeks
measure: Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Total Scores - Initiation Period
timeFrame: Baseline, week 12, and week 16
measure: Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 1 Period
timeFrame: Baseline, 16, 24 and 48 weeks
measure: Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 2 Period
timeFrame: Baseline, 48 and 72 weeks
measure: Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Initiation Period
timeFrame: Baseline, 12 and 16 weeks
measure: Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 1 Period
timeFrame: Baseline, 16, 24 and 48 weeks
measure: Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 2 Period
timeFrame: Baseline, 48 and 72 weeks
Other outcomes:
Locations:
city: Cork
country: Ireland
facility: Novartis Investigative Site
city: Dublin 4
country: Ireland
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Plymouth
country: United Kingdom
facility: Novartis Investigative Site
state: Devon
city: London
country: United Kingdom
facility: Novartis Investigative Site
state: England
city: Harlow
country: United Kingdom
facility: Novartis Investigative Site
state: Essex
city: London
country: United Kingdom
facility: Novartis Investigative Site
state: GBR
city: Canterbury
country: United Kingdom
facility: Novartis Investigative Site
state: Kent
city: Dafen
country: United Kingdom
facility: Novartis Investigative Site
state: Llanelli
city: Salford
country: United Kingdom
facility: Novartis Investigative Site
state: Manchester
city: Cliftonville
country: United Kingdom
facility: Novartis Investigative Site
state: Northampton
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
state: Nottinghamshire
city: Aberdeen
country: United Kingdom
facility: Novartis Investigative Site
state: Scotland
city: Yeovil
country: United Kingdom
facility: Novartis Investigative Site
state: Somerset
city: Cardiff
country: United Kingdom
facility: Novartis Investigative Site
state: South Glamorgan
city: Ipswich
country: United Kingdom
facility: Novartis Investigative Site
state: Suffolk
city: Frimley
country: United Kingdom
facility: Novartis Investigative Site
state: Surrey
city: Rhyl
country: United Kingdom
facility: Novartis Investigative Site
state: Wales
city: Coventry
country: United Kingdom
facility: Novartis Investigative Site
state: Warwickshire
city: Dudley
country: United Kingdom
facility: Novartis Investigative Site
state: West Midlands
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Airdrie
country: United Kingdom
facility: Novartis Investigative Site
city: Bath
country: United Kingdom
facility: Novartis Investigative Site
city: Belfast
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Birmingham
country: United Kingdom
facility: Novartis Investigative Site
city: Chester
country: United Kingdom
facility: Novartis Investigative Site
city: Durham
country: United Kingdom
facility: Novartis Investigative Site
city: Fife
country: United Kingdom
facility: Novartis Investigative Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigative Site
city: Hull
country: United Kingdom
facility: Novartis Investigative Site
city: Lancaster
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Middlesborough
country: United Kingdom
facility: Novartis Investigative Site
city: Middlesex
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Norwich
country: United Kingdom
facility: Novartis Investigative Site
city: Nottingham
country: United Kingdom
facility: Novartis Investigative Site
city: Oxford
country: United Kingdom
facility: Novartis Investigative Site
city: Poole
country: United Kingdom
facility: Novartis Investigative Site
city: Portsmouth
country: United Kingdom
facility: Novartis Investigative Site
city: Scaroborough
country: United Kingdom
facility: Novartis Investigative Site
city: Scunthorpe
country: United Kingdom
facility: Novartis Investigative Site
city: Staffordshire
country: United Kingdom
facility: Novartis Investigative Site
city: Stoke-on-Trent
country: United Kingdom
facility: Novartis Investigative Site
city: Surrey
country: United Kingdom
facility: Novartis Investigative Site
city: Surrey
country: United Kingdom
facility: Novartis Investigative Site
city: Wrexham
country: United Kingdom
facility: Novartis Investigative Site
city: York
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: