Phase III Study of Efficacy and Safety of Secukinumab Versus Placebo, in Combination With Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR)

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate the efficacy and safety of secukinumab 300 milligram (mg) and 150 mg administered subcutaneously (s.c.) for 52 weeks in combination with prednisone tapered over 24 weeks in adult participants with PMR who have recently relapsed.

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study with two secukinumab dose regimens in approximately 360 PMR patients who had recently relapsed. The study consists of: screening (up to 6 weeks); treatment period (52 weeks, with last IMP administration at 48 weeks, active drug or placebo) in combination with prednisone tapered over 24 weeks; treatment-free follow-up (up to 24 weeks). Adult males and females of at least 50 years of age with a recent PMR relapse (within 12 weeks from Baseline) will be included. Dosing will be once every week for the first 4 weeks, and once every 4 weeks thereafter via pre-filled syringe. The primary objective is to demonstrate the efficacy of secukinumab 300 mg subcutaneously in combination with a 24-week glucocorticoid (GC) taper regimen compared with placebo with respect to the proportion of patients in sustained remission at Week 52. Primary secondary objectives are to assess difference in proportion of patients achieving complete sustained remission at Week 52, adjusted annual cumulative GC dose and time to first use of escape treatment or rescue treatment through Week 52. Key safety data will be collected, along with Patient Reported Outcomes.

Official Title
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A Randomized, Parallel-group, Double-blind, Placebo-controlled, Multicenter Phase III Trial to Evaluate Efficacy and Safety of Secukinumab Administered Subcutaneously Versus Placebo, in Combination With a Glucocorticoid Taper Regimen, in Patients With Polymyalgia Rheumatica (PMR)

Conditions
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Polymyalgia Rheumatica

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study Male or non-pregnant, non-lactating female participants at least 50 years of age. Diagnosis of PMR according to the provisional American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria: Participants ≥ 50 years of age with a history of bilateral shoulder pain accompanied by elevated C-reactive protein (CRP) concentration (≥ 10 mg/L) and/or elevated erythrocyte sedimentation rate (ESR) (≥ 30 mm/hr) who scored at least 4 points from the following optional classification criteria: Morning stiffness > 45 minutes (min) (2 points) Hip pain or restricted range of motion (1 point) Absence of rheumatoid factor and/or anti-citrullinated protein antibodies (2 points) Absence of other joint involvement (1 point) Participants must have a history of being treated for at least 8 consecutive weeks with prednisone (≥ 10 mg/day or equivalent) at any time prior to screening Participants must have had at least one episode of PMR relapse while attempting to taper prednisone at a dose that is ≥ 5 mg/day (or equivalent) within the past 12 weeks prior to BSL. Diagnosis of a PMR relapse is defined as participant meeting both of the following: Recurrence of bilateral shoulder girdle and/or bilateral hip girdle pain associated with inflammatory stiffness with or without additional symptoms indicative of PMR relapse (such as constitutional symptoms) within 12 weeks prior to BSL that are in the opinion of the Investigator not due to other diseases that may mimic PMR such as osteoarthritis in shoulders or hips, polyarticular calcium pyrophosphate deposition disease, rotator cuff disease, adhesive capsulitis (frozen shoulder) or fibromyalgia. Elevated ESR (≥ 30 mm/hr) and/or elevated CRP (> upper limit of normal (ULN)) attributable to PMR at the time of relapse and/or at screening Participants must have been treated as per local treatment recommendations following the latest PMR relapse and must be on prednisone of at least 7.5 mg/day (or equivalent) and not exceeding 25 mg/day at screening and during the screening period Exclusion Criteria: Evidence of GCA as indicated by typical (cranial) symptoms (e.g., persistent or recurrent localized headache, temporal artery or scalp tenderness, jaw claudication, blurry or loss of vision, symptoms of stroke), extremity claudication, imaging and/or temporal artery biopsy result Concurrent rheumatoid arthritis or other inflammatory arthritis or other connective tissue diseases, such as but not limited to systemic lupus erythematosus, systemic sclerosis, vasculitis, myositis, mixed connective tissue disease, and ankylosing spondylitis Concurrent diagnosis or history of neuropathic muscular diseases Inadequately treated hypothyroidism (e.g., persistence of symptoms, lack of normalization of serum TSH despite regular hormonal replacement treatment) Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 receptor Participants treated with tocilizumab or other IL-6/IL6-receptor inhibitors within 12 weeks or within 5 half-lives (whichever is longer) prior to BSL; participant who did not respond to or experienced a relapse during treatment are excluded from enrollment into the study Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 50 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 300 mg<br>randomized in 1:1:1 ratio every 4 weeks | Drug: Secukinumab 300 mg<br>* Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen<br>* Other names: AIN457;|
| Experimental: Secukinumab 150 mg<br>randomized in 1:1:1 ratio every 4 weeks | Drug: Secukinumab 150 mg<br>* Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen<br>* Other names: AIN457;|
| Placebo Comparator: Placebo to secukinumab<br>randomized in 1:1:1 ratio every 4 weeks | Other: Placebo to secukinumab<br>* Taken subcutaneously every 4 weeks until Week 48 in combination with a 24-week prednisone taper regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving sustained remission | Sustained remission at Week 52 is defined as a participant meeting all of the following: ● achieved remission at Week 12 AND all of the following, sustained from Week 12 to Week 52: no recurrence of signs or symptoms, attributable to PMR, that requires escape treatment or rescue treatment no new diagnosis of Giant cell arteritis (GCA), that requires escape treatment or rescue treatment Remission at Week 12 is defined as a participant meeting all of the following at Week 12: no use of escape treatment or rescue treatment prior to Week 12 no signs or symptoms attributable to PMR, that requires escape treatment or use of rescue treatment, at Week 12 no new diagnosis of GCA, that requires escape treatment or rescue treatment, at Week 12 | at Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving complete sustained remission | Complete sustained remission at Week 52 is defined as participant meeting all of the following: achieved sustained remission no clinically relevant elevation of Erythrocyte sedimentation Rate (ESR) and/or C-reactive protein (CRP) at ≥2 consecutive scheduled visits from Week 12 to Week 52 | 52 Weeks | 
| Adjusted annual cumulative glucocorticoid (GC) dose adjusted by duration of study follow-up | Adjusted annual cumulative GC dose is cumulative GC dose through Week 52 adjusted by duration of study follow-up | 52 Weeks | 
| Time to first use of escape treatment or rescue treatment as measured in days | First use of escape treatment or rescue treatment is defined as the first time when the escape treatment or rescue treatment is used | 52 Weeks | 
| Change in FACIT-Fatigue Score | The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. The purpose of collecting available FACIT-Fatigue data is to assess the impact of fatigue on participants with PMR. | 52 Weeks | 
| Change in HAQ-DI score | The Health Assessment Questionnaire - Disability Index (HAQ-DI) is used to assess the long-term influence of chronic disease on a participant's level of functional ability and activity restriction. The purpose of the HAQ-DI is to assess the functional ability of subjects with PMR. | 52 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal antibody, prednisone taper regimen, glucocorticoid, PMR, Polymyalgia Rheumatica, secukinumab