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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01961609
Recruitment Status : Completed
First Posted : October 11, 2013
Results First Posted : March 18, 2019
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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.

Condition or disease Intervention/treatment Phase
Psoriasis Biological: Secukinumab (AIN457) Phase 3

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 235 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 9, 2013
Actual Primary Completion Date : July 12, 2016
Actual Study Completion Date : July 12, 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Psoriasis
Drug Information available for: Secukinumab

Arm Intervention/treatment
Experimental: Secukinumab (AIN457) 300 mg
Participants self-administered 300 mg secukinumab loading dose subcutaneously at Day 0 (initiation of study drug) and at weeks 1, 2, 3 & 4, and then every 4 weeks. Following the Primary Endpoint at 16 weeks, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 32 weeks. Participants not meeting this NICE criterion returned to routine treatment under the care of their usual Clinical Team. Following assessment at week 48, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 24 weeks. Participants not meeting this NICE criterion returned to routine treatment under the care of their usual Clinical Team.
Biological: Secukinumab (AIN457)
Secukinumab was supplied in 150mg pre-filled syringes.

Experimental: Secukinumab (AIN457) 150 mg
Participants self-administered secukinumab 150 mg loading dose subcutaneously at Day 0 (initiation of study drug), weeks 1, 2, 3 & 4 and then every 4 weeks. Following the Primary Endpoint at 16 weeks, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 32 weeks at the 150mg dose. Participants not achieving the NICE criteria at the Primary Endpoint were up titrated to 300mg. Following assessment at week 48, participants meeting the NICE criteria of adequate response were eligible to continue on study treatment for a further 24 weeks at the 150mg dose. Participants not achieving the NICE criteria at 48 weeks on the 150mg dose were up titrated to 300mg.
Biological: Secukinumab (AIN457)
Secukinumab was supplied in 150mg pre-filled syringes.




Primary Outcome Measures :
  1. Percentage of Secukinumab 300 mg Participants Achieving PASI 75 at 16 Weeks [ Time Frame: 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.


Secondary Outcome Measures :
  1. Percentage of Secukinumab 150 mg Participants Achieving PASI 75 at 16 Weeks [ Time Frame: 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.

  2. 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 [ Time Frame: 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.

  3. Percentage of Participants Achieiving PASI 75 - Initiation Period [ Time Frame: 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 defined as participants achieving ≥ 75% improvement from baseline.

  4. Percentage of Participants Achieiving PASI 75 - Maintenance 1 Period [ Time Frame: 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 defined as participants achieving ≥ 75% improvement from baseline.

  5. Percentage of Participants Achieiving PASI 75 - Maintenance 2 Period [ Time Frame: 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 defined as participants achieving ≥ 75% improvement from baseline.

  6. Percentage of Participants Achieving PASI 50 and PASI 90 - Initiation Period [ Time Frame: 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 PASI 90 are defined as participants achieving ≥ 50% and ≥ 90% improvement from baseline, respectively.

  7. Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 1 Period [ Time Frame: 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 PASI 90 are defined as participants achieving ≥ 50% and ≥ 90% improvement from baseline, respectively.

  8. Percentage of Participants Achieving PASI 50 and PASI 90 - Maintenance 2 Period [ Time Frame: 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 PASI 90 are defined as participants achieving ≥ 50% and ≥ 90% improvement from baseline, respectively.

  9. Percentage of Participants Who Have Failed on One Anti-TNFα Achieving PASI 75 (Subgroups 1 and 2 Combined) at 16 Weeks [ Time Frame: 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.

  10. Percentage of Participants Achieving NICE Continuation Criteria (PASI 75 or PASI 50 Plus a 5 Point Improvement in DLQI) at 16 Weeks [ Time Frame: 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.

  11. Mean Change From Baseline in Dermatology Life Quality Index (DLQI) Total Scores - Initiation Period [ Time Frame: 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 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.

  12. Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 1 Period [ Time Frame: Baseline, 16, 24 and 48 weeks ]
    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.

  13. Mean Change From Baseline in Dermatology Life Quality Index (DLQI)Total Scores - Maintenance 2 Period [ Time Frame: Baseline, 48 and 72 weeks ]
    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.

  14. Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Initiation Period [ Time Frame: Baseline, 12 and 16 weeks ]
    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.

  15. Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 1 Period [ Time Frame: Baseline, 16, 24 and 48 weeks ]
    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.

  16. Mean Percent Change in EuroQOL 5-Dimension Health Status Questionnaire (EQ-5D) Health State Assessment Scores (From 0 to 100) - Maintenance 2 Period [ Time Frame: Baseline, 48 and 72 weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01961609


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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01961609     History of Changes
Other Study ID Numbers: CAIN457AGB01
First Posted: October 11, 2013    Key Record Dates
Results First Posted: March 18, 2019
Last Update Posted: March 18, 2019
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Chronic plaque psoriasis

Additional relevant MeSH terms:
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Psoriasis
Skin Diseases, Papulosquamous
Skin Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs