A Biomarker Study of Secukinumab in Rheumatoid Arthritis (RA) Patients

Study Overview
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Brief Summary
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This study aims to confirm if patients with a specific biomarker might have a better response to secukinumab treatment. To meet this purpose, exploratory biomarker studies will be done. The goals of these exploratory studies are to (1) find biomarkers that will identify persons with rheumatoid arthritis who will have the best possible response to secukinumab and (2) to identify persons who will have fewer side effects in order to maximize their benefit from secukinumab.

Official Title
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A Multicenter, 12 Week, Randomized, Double-blind, Placebo-controlled Biomarker Study of Secukinumab (AIN457) in Rheumatoid Arthritis Patients Followed by an Open Label Extension

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Placebo
* Drug: Secukinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of rheumatoid arthritis Patients must be either DMARD naive or have failed at least one DMARD agent (e.g. MTX, leflunamide or sulfasalazine) Patients are allowed up to 3 DMARDs at study entry (e.g. MTX, sulfasalazine or hydroxychloroquine) as long as their dose was stable for 4 weeks prior to initiating study treatment Disease activity at screening defined by ≥6 out of 28 tender joints and ≥6 out of 28 swollen joints and hsCRP >10mg/L Exclusion Criteria: Patients with severe rheumatoid arthritis (functional status class IV according to the ACR 1991 revised criteria) Previous exposure to secukinumab or any other biologic, including TNF inhibitors. Use of high potency opioid analgesics Pregnant or nursing (lactating) women Use of any investigational drug other than RA therapy and/or devices at the time of randomization or within 30 days or 5 half-lives of randomization, whichever is longer. Other protocol-defined inclusion/exclusion criteria may apply

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Secukinumab<br>10 mg/kg intravenous (I.V.) | Drug: Secukinumab<br>* In part 1 (blinded period), participants randomized to secukinumab received 10 mg/kg I.V.. Participants, enrolled in part 2 (open label), received secukinumab 300 mg subcutaneous.<br>* Other names: AIN457;|
| Placebo Comparator: Placebo<br>Placebo I.V. | Drug: Placebo<br>* Matching placebo to secukinumab I.V.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve American College of Rheumatology Response of 20 (ACR20 ) in Association With the Presence or Absence of the HLA-DRB1 *4 Allelic Group | A participant was considered to be a responder according to the ACR20 criteria if the participant had at least 20% improvement in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). | 12 weeks | 
| Change From Baseline in Disease Activity Score 28 (DAS28) in Association With the Presence or Absence of HLA-DRB1 04 | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | baseline, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve ACR50 and ACR70 With the Presence/Absence of the HLA-DRB1*04 Allelic Group | A participant was considered to be a responder according to the ACR50 or ACR70 criteria if the participant had at least 50% or 70% improvement, respectively, in both the tender joint count and swollen joint count measures, and in at least 3 of the following 5 measures: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, Health Assessment Questionnaire (HAQ©) score, and/or C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR). | 12 weeks | 
| Change From Baseline in DAS28 in Association With the Presence or Absence of HLA-DRB1 *SE (Positive), HLA-DRB1 *401 (Carrier) and HLA-DRB1 Position 11 V/L and in Association With Other Biomarkers | The DAS28 is a measure of disease activity in RA. The score is calculated by a complex mathematical formula, which includes the tender joint count(TJC) and swollen joint count (SJC) out of a total of 28 joints, the high-sensitivity C-reactive protein (hsCRP), and the subject's 'global assessment' of disease activity/general health (GH). The subject's global assessment/GH was indicated by a visual analogue scale of 100 mm where the participant marked a point on a 100 mm line between 0 and 100 (0 indicated very good and 100 indicated very bad). The following formula was used to calculate DAS28: DAS-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) = 0.36*ln(CRP+1) + 0.014*GH = 0.96. A DAS28-CRP score > 5.1 implies active disease, <3.2 implies controlled disease and <2.6 implied remission. A negative change from baseline indicates improvement. | baseline, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, IgG1K monoclonal antibody, Interleukin-17A neutralizing