24 Week Efficacy and 3-year Safety and Efficacy of Secukinumab in Active Psoriatic Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to provide 24 - 52 week efficacy, safety and tolerability data, and up to 3-year efficacy, safety and tolerability data in subjects with active Psoriatic Arthritis despite current or previous nonsteroidal anti-inflammatory drug (NSAID), disease-modifying antirheumatic drug (DMARD) therapy and/or previous anti-tumor necrosis factor alpha (TNFα) therapy.

Official Title
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A Phase III, Randomized, Double-blind, Placebo-controlled Multicenter Study of Subcutaneous Secukinumab in Autoinjectors, to Demonstrate Efficacy at 24 Weeks and to Assess the Long Term Safety, Tolerability and Efficacy up to 3 Years in Subjects With Active Psoriatic Arthritis

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Biological: Secukinumab
* Biological: 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. 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 (AIN457) 150 mg s.c.<br>1 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4. | Biological: Secukinumab<br>* Secukinumab 150 mg provided in a 1 mL autoinjector (1 autoinjector for 150 mg dose, 2 autoinjectors for 300 mg dose)<br>* Other names: Secukinumab 300 mg;|
| Experimental: Secukinumab (AIN457) 300 mg s.c.<br>2 s.c. Secukinumab 150 mg autoinjector at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4. | Biological: Secukinumab<br>* Secukinumab 150 mg provided in a 1 mL autoinjector (1 autoinjector for 150 mg dose, 2 autoinjectors for 300 mg dose)<br>* Other names: Secukinumab 300 mg;|
| Placebo Comparator: Placebo<br>Matching Placebo at Baseline, Weeks 1, 2, 3, 4, followed by dosing every four weeks starting at Week 4. | Biological: Placebo<br>* Secukinumab placebo provided in 1 mL autoinjector<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving American College of Rheumatology 20 (ACR20) Response Criteria on Secukinumab Versus Placebo at Week 24 | A patient will be considered as improved according the ACR20 criteria if she/he has at least 20% decrease in the swollen and tender joint count, and at least 20% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)] | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Achieving American College of Rheumatology 50 (ACR50) Response Criteria on Secukinumab Versus Placebo at Week 24 | A patient will be considered as improved according the ACR50 criteria if she/he has at least 50% decreases in the swollen and tender joint count, and at least 50% improvements in 3 of the following 5 criteria: physical disability on the Health Assessment Questionnaire; pain score on a visual analog scale; patient global assessment; physician global assessment; and acute phase reactant [either erythrocyte sedimentation rate (ESR) or high sensitivity C-reactive protein (hsCRP)] | Week 24 | 
| Change From Baseline in Disease Activity Score for 28 Joints (DAS28-CRP) (Utilizing hsCRP) in Subjects Treated With Secukinumab Versus Placebo at Week 24 | DAS28-CRP is a measure of disease activity based on 28-Swollen and Tender Joint Count [proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2)], CRP, and the Patient's Global Assessment of disease activity. Values range from 2.0 to 10.0 where higher values mean a higher disease activity. DAS28-CRP < 2.6 is interpreted as remission. | Week 24 | 
| Proportion of Subjects Achieving a Psoriatic Area and Severity Index 75 (PASI75) Response in Subjects on Secukinumab Versus Placebo at Week 24 | PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI75 represents an improvement in the PASI score of at least 75% as compared with baseline. | Week 24 | 
| Change From Baseline in Physical Function Component of the Short-form Health Survey (SF-36-PCS) in Subjects Treated With Secukinumab Versus Placebo at Week 24 | 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. | Week 24 | 
| Percentage of Subjects Achieving a Psoriatic Area and Severity Index 90 (PASI90) Response in Subjects Treated With Secukinumab Versus Placebo at Week 24 | PASI takes into account the extent of the disease, as well as the severity of erythema, scaling, and thickness in different body areas affected by psoriasis. A PASI90 represents an improvement in the PASI score of at least 90% as compared with baseline. | Week 24 | 
| Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI Score) in Subjects Treated With Secukinumab Versus Placebo at Week 24 | The HAQ measures physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects and dollar costs. In this trial, only the disability dimension was used. The disability dimension consists of 20 multiple choice items concerning difficulty in performing 8 common activities of daily living; dressing and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. Participants choose from four response categories: 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty) and 3 (unable to do). Within each of the 8 categories, only the item indicating the most severe impairment contributes to the category score. The HAQ score is calculated by summing the computed scores for each category and dividing by the number of categories answered. It ranges from 0 (without any difficulty) to 3 (unable to do). A negative change from baseline indicates improvement. | Week 24 | 
| Proportion of Patients With Dactylitis at Week 24 in the Subset of Patients Who Had Dactylitis at Baseline | The presence of dactylitis was assessed by dactylitis count (number of fingers and toes with dactylitis, with a range of 0-20). If dactylitis is present with any finger or toe, the patient is counted as a patient with dactylitis. | Week 24 | 
| Proportion of Patients With Enthesitis at Week 24 in the Subset of Patients Who Had Enthesitis at Baseline | The presence of Enthesitis was assessed using a validated enthesitis index that uses 6 sites for evaluation of enthesitis: lateral epicondyle humerus L + R, proximal achilles L + R and medial condyle femur. If enthesitis is present at any of the 6 sites, the subject is counted as a subject with enthesitis. | Week 24 | 
| Number of Participants With Treatment Emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by Primary System Organ Class (SOC) | Analysis of frequencies for treatment emergent Adverse Event (AE), Serious Adverse Event (SAE) and Deaths by primary System Organ Class (SOC). | From first dose of study treatment to last study visit, up to 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriatic arthritis, AIN457, PsA, ACR, CASPAR, PASDAS, secukinumab, autoinjector