16-week Efficacy and 2-year Safety, Tolerability and Efficacy of Secukinumab in Participants With Active Psoriatic Arthritis

Study Overview
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Brief Summary
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The purpose of this study was to provide 16-week efficacy, safety and tolerability data versus placebo to support the use of secukinumab 150 mg by subcutaneous (s.c.) self-administration with or without a loading regimen and maintenance dosing using pre-filled syringe (PFS) and to assess efficacy, safety and tolerability up to 2 years in subjects with active PsA despite current or previous NSAID or DMARD therapy

Official Title
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A Phase III, Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab (150 mg) in Pre-filled Syringe, With or Without Loading Regimen, to Demonstrate Efficacy, Safety and Tolerability up to 2 Years in Patients With Active Psoriatic Arthritis (FUTURE 4)

Conditions
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Arthritis, Psoriatic

Intervention / Treatment
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* Biological: Secukinumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Psoriatic Arthritis (PsA) classified by ClASsification criteria for Psoriatic ARthritis (CASPAR) criteria. Rheumatoid factor and anti-cyclic citrullinated peptide (CCP) antibodies negative. Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis. Inadequate control of symptoms with NSAID. Other protocol-defined inclusion criteria do apply. Exclusion Criteria: Chest X-ray or chest magnetic resonance imaging (MRI) with evidence of ongoing infectious or malignant process. Subjects taking high potency opioid analgesics. Previous exposure to secukinumab or other biologic drug directly targeting interleukin-17 (IL-17) or IL-17 receptor. Ongoing use of prohibited psoriasis treatments / medications. Subjects who have ever received biologic immunomodulating agents except for those targeting TNFα. Previous treatment with any cell-depleting therapies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab 150 mg<br>Secukinumab 150 mg s.c. with loading: Secukinumab 150 mg at Baseline, Weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | Biological: Secukinumab<br>* Secukinumab 150 mg (1 mL liquid formulation) in pre-filled syringes were supplied by Novartis. Each secukinumab 300 mg dose was given as two sc injections of secukinumab 150 mg.<br>|
| Experimental: Secukinumab 150 mg No load<br>Secukinumab 150 mg s.c. without loading: Secukinumab 150 mg at baseline, followed by dosing every four weeks starting at Week 4, with Placebo at Weeks 1, 2 and 3. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | Biological: Secukinumab<br>* Secukinumab 150 mg (1 mL liquid formulation) in pre-filled syringes were supplied by Novartis. Each secukinumab 300 mg dose was given as two sc injections of secukinumab 150 mg.<br>|
| Placebo Comparator: Placebo<br>Placebo to Secukinumab at Baseline, Weeks 1, 2 and 3, followed by dosing every four weeks starting at Week 4 until Week 16/24, depending on patients responder status. From Week 16/24, patients were switched to Secukinumab 150 mg every four weeks. After primary outcome evaluation, approval and implementation of Amendment 2 Secukinumab dose may have been escalated to 300 mg as judged appropriate by the investigator | Other: Placebo<br>* Placebo to secukinumab was also available in 1.0 mL liquid formulation in prefilled syringe to match the active drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With American College of Rheumatology 20 (ACR20) Response | The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Disability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score (DAS-C28-CRP) Score Change From Baseline Using MMRM at Week 16 | DAS28-CRP score change from baseline using MMRM up to Week 16. DAS-CRP values range between 2.0 and 10. The higher the score, the higher the disease severity. n: Number of subjects with measures at both baseline and the corresponding post baseline visit. | week 16 | 
| Psoriatic Area and Severity Index 75 (PASI75) | PASI is a measure of disease activity based on extent of the disease, severity of erythema, scaling and thickness in different body areas affected by psoriasis. PASI75 is an improvement in the PASI score of at least 75% compared to baseline. PASI75 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. PASI75 response using non-responder imputation and rescue penalty up to Week 16 | 16 weeks | 
| Short Form Health Survey Physical Component Score (SF-36-PCS) | SF-36 is a 36 item questionnaire which measures Quality of Life across eight domains, which are both physically and emotionally based. Two overall summary scores, the Physical Component Summary (PCS) and Mental Component Summary (MCS) can be computed. In this study, SF-36 PCS is used to assess improvement from baseline of at least one dose of secukinumab versus placebo. The SF-36 is a validated instrument measuring health-related quality of life across multiple disease states. It has 36 questions with 8 subscale scores and 2 summary scores (1) physical component summary=physical functioning, role-physical, bodily pain, and general health. There is no total overall score; scoring is done for both subscores and summary scores. For subscores and summary scores, 0 =worst score (or quality of life) and 100=best score. Change from Baseline= post-Baseline - Baseline value. | 16 weeks | 
| Number of Participants With American College of Rheumatology 50 (ACR50) | The ACR50 response is defined by at least 50% decrease in the swollen and tender joint count, and at least 50% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR50 is used to assess the efficacy of secukinumab, with or without loading, versus placebo. This table is the ACR50 response using non-responder imputation and rescue penalty up to Week 16 | 16 weeks | 
| Number of Participants With American College of Rheumatology 20 (ACR20) Response | The ACR20 response is defined by at least 20% decrease in the swollen and tender joint count, and at least 20% improvement in 3 of the following 5 criteria: Health Assessment Questionnaire - Diability Index, pain score on a visual analog scale, patient global assessment of disease activity, physician global assessment of disease activity and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)]. ACR20 is used to assess the efficacy of secukinumab, with or without loading, versus placebo | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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secukinumab, self-injection, AIN457, psoriatic arthritis, chronic inflammatory disease, loading regimen