Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis (PsA) After 16 Weeks of Treatment Compared to Placebo

Study Overview
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Brief Summary
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To demonstrate that the efficacy of secukinumab 300 mg at Week 16 was superior to placebo in adult patients with active PsA based on the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response.

Detailed Description
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Treatment Period 1 was defined as the period from Randomization through Week 16 (prior to the Week 16 dose). At the start of placebo-controlled Treatment Period 1, patients were randomized via Interactive Response Technology (IRT) in a 2:2:1 ratio to 1 of 3 treatment groups. Group 1- Secukinumab 300 mg: secukinumab 300 mg (2 s.c. injections of the 150-mg dose) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. Group 2- Secukinumab 150 mg: secukinumab 150 mg (1 s.c. injection of the 150-mg dose and 1 s.c. injection of placebo) once weekly for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. Group 3- Placebo: placebo (2 s.c. injections of 150 mg secukinumab placebo per dose) once per week for 5 weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every 4 weeks. At each study treatment visit 2 s.c. injections in the form of prefilled syringes (PFS) were administered. This was necessary to maintain the blind, as secukinumab in PFS is available in either 1.0 mL (150 mg) or 2 x 1.0 mL (300 mg). Placebo to secukinumab was also available in 1.0 mL to match the active drug. Rescue medication was not allowed before completion of Week 16 assessments. Treatment Period 2 patients receiving secukinumab 300 mg (Group 1) continued to receive the same dose up to Week 48. At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) were classified as responders (≥20% improvement from BL in both tender and swollen joint counts) or nonresponders. At Weeks 16, 28, and 40 patients on secukinumab 150 mg (Group 2) who were responders continued to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 mL) every 4 weeks until next evaluation of responder status at Weeks 28 or 40. Patients who did not meet the responder criteria at Week 16, 28, or 40 started receiving secukinumab 300 mg s.c. every 4 weeks and continued this dose up to Week 48. Patients on placebo (Group 3) regardless of their responder status started receiving secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis After 16 Weeks of Treatment Compared to Placebo and to Assess the Safety, Tolerability and Efficacy up to 52 Weeks

Conditions
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Psoriatic Arthritis

Intervention / Treatment
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* Drug: Secukinumab 300 mg
* Drug: Secukinumab 150 mg
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or non-pregnant, non-lactating female patients at least 18 years of age Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months with moderate to severe PsA who must have at Baseline ≥3 tender joints out of 78 and ≥3 swollen out of 76 (dactylitis of a digit counts as one joint each) Rheumatoid factor and/or anti-CCP antibodies negative at screening A target skin psoriatic lesion and a PASI score of 1 or greater Exclusion Criteria: Chest X-ray with evidence of ongoing infectious or malignant process Patients who ever received biologic immunomodulating agents including those targeting TNFα, IL-6 and IL-12/23 investigational or approved

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
Interventional Model Description: Study design displays results combined as two or more Arms/Groups. Patients assigned to Placebo arm in Treatment Period 1 (TP1) may have switched to Secukinumab 300mg in Treatment Period 2 (TP2). Summaries by group were performed cumulatively by actual treatment received (as follows) for every visit until Week 16 groups in Treatment Period 1: · Secukinumab 300mg (Group 1) · Secukinumab 150mg (Group 2) · Placebo (Group 3) For entire treatment period, summaries by treatment group were performed cumulatively by the actual treatment received (as follows) for every visit til Week 52, including patients who switched at Weeks 16, 28, 40. For safety variables · Any Secukinumab 150 mg (Group 2) · Any Secukinumab 300mg (Group 1) · Any Secukinumab (Group 3) Hence, participants who received Placebo in TP1 were combined with participants who received Any Secukinumab in Group 3 and Any Secukinumab 300mg in Group 1 in TP2. Safety is presented for the ENTIRE period, including TP1 and TP2
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>secukinumab 300mg s.c. injection | Drug: Secukinumab 300 mg<br>* 150 mg x 2 s.c. injection<br>* Other names: AIN457;|
| Active Comparator: Group 2<br>secukinumab 150 mg s.c. injection | Drug: Secukinumab 150 mg<br>* 150 mg s.c. injection<br>* Other names: AIN457;|
| Placebo Comparator: Group 3<br>Placebo s.c. injection | Other: Placebo<br>* Placebo<br>* Other names: s.c. injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Patients Achieving American College of Rheumatology Score of at Least 20% (ACR20) Response Criteria on Secukinumab 300 mg and 150 mg vs. Placebo at Week 16 | A patient was considered as improved according to the ACR20 criteria if she/he had at least 20% improvement in two of the following measures:Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity, Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR). Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients With Dactylitis in the Subset of Subjects Who Have Dactylitis at Week 16 | The percent of patients in the Dactylitis Subset with dactylitis in the secukinumab 300 mg group at Week 16. Dactylitis is severe inflammation of the finger and toe joints. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | Week 16 | 
| Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Baseline (SPARCC) at Week 16 | Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 
| Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (LEI) | Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. LEI=Leeds Enthesitis Index | 16 Weeks | 
| Percentage of Patients With Enthesitis in the Subset of Subjects Who Have Enthesitis at Week 16 (Combined SPARCC and LEI) | Statistical analysis (logistic regression) of presence of enthesitis (Combined SPARCC and LEI) by visit - in treatment period 1 (non-responder imputation) (Combined SPARCC and LEI Subset) Enthesitis, also called enthesopathy, is inflammation of the entheses, the sites where tendons or ligaments insert into the bone. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 
| Percentage of Patients Achieving ACR50 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16 | A patient was considered as improved according the ACR50 criteria if she/he had at least 50% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR50 response by visit - in treatment period 1 (non-responder imputation) (Full Analysis Set) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 
| Percentage of Patients Achieving ACR70 Response Criteria on Secukinumab 300 or 150 mg vs. Placebo at Week 16 | A patient was considered as improved according the ACR70 criteria if she/he had at least 70% improvement in the two of the following measures: Tender joint count, Swollen joint count and at least 3 of the following 5 measures: Patient's assessment of pain, Patient's global assessment disease activity,Physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score,Acute phase reactant (hsCRP or ESR) Statistical analysis (logistic regression) of ACR70 response by visit - in treatment period 1 (non-responder imputation) Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 
| Percentage of Patients Achieving a PASI75 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 | A 75% reduction in the Psoriasis Area and Severity Index (PASI) score (PASI 75) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis. | 16 Weeks | 
| Percentage of Patients Achieving a PASI90 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 | A 90% reduction in the Psoriasis Area and Severity Index score (PASI 90) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis. | 16 Weeks | 
| Percentage of Patients Achieving a PASI100 Response in the Subgroup of Subjects Who Have ≥3% Skin Involvement With Psoriasis at Week 16 | A 100% reduction in the Psoriasis Area and Severity Index score (PASI 100) is above the current benchmark of primary endpoints for most clinical trials with endpoints of psoriasis. Odds ratio, 95% confidence interval for odds ratio, and p-value are from a logistic regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no) and body weight (kg) as explanatory variables. | 16 Weeks | 
| Change From Baseline to Week 16 in DAS28-CRP | DAS-CRP uses the C-Reactive Protein (CRP) value. Disease Activity Score (DAS28-CRP) values range from 2.0 to 10.0 while higher values mean a higher disease activity. A DAS28-CRP below the value of 2.6 is interpreted as Remission. DAS28-CRP uses 28 different joints for its calculation: proximal interphalangeal joints (10 joints) metacarpophalangeal joints (10) wrists (2) elbows (2) shoulders (2) knees (2) With the above mentioned parameters. Least squares mean (LSM), Least squares mean (LSM) treatment difference, 95% confidence interval (CI) for treatment difference, and p-values are from an analysis of covariance (ANCOVA) model with treatment (3 treatment groups), baseline DAS28-CRP score, methotrexate usage at baseline (yes, no), and body weight(kg) as explanatory variables. | baseline, 16 weeks | 
| Change From Baseline to Week 16 in HAQ-DI | The Health assessment questionnaire disability index (HAQ-DI) is 20-question instrument that assesses the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area are scored from 0 (no difficulty), to 3 (inability to perform a task in that area). The average score across the functional areas yields an overall HAQ score which ranges from 0 (no disability) to 3 (completely disabled). | 16 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PsA, ACR, CASPAR, inflammatory arthritis, spondylitis