Evaluation of the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Evaluation of the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Primary Objective:

 To evaluate the efficacy of KEVZARA (sarilumab) in patients with polymyalgia rheumatica (PMR)
 as assessed by the proportion of subjects with sustained remission for sarilumab with a
 shorter corticosteroid (CS) tapering regimen as compared to placebo with a longer CS tapering
 regimen.

 Secondary Objectives:

 -  To demonstrate the efficacy of sarilumab in patients with polymyalgia rheumatica
 compared to placebo, in combination with a CS taper with regards to:

 -  Clinical responses (such as components of sustained remission, disease remission rates,
 time to first disease flare) over time.

 -  Cumulative CS (including prednisone) exposure.

 -  To assess the safety (including immunogenicity) and tolerability of sarilumab in
 patients with PMR.

 -  To measure sarilumab serum concentrations in patients with PMR.

 -  To assess the effect of sarilumab in reducing glucocorticoid toxicity as measured by the
 composite glucocorticoid toxicity index (GTI) questionnaire.
Study duration per participant is approximative 62 weeks including up to a 4-week screening
 period, 52-week treatment period and 6-week follow-up period.
Inclusion criteria :

 -  Diagnosis of polymyalgia rheumatica (PMR) according to European League Against
 Rheumatism/American College of Rheumatology classification criteria.

 -  Patients must be on prednisone of at least 7.5 mg/day (or equivalent) and not
 exceeding 20 mg/day at screening and during the screening period.

 -  Patient is willing and able to take prednisone of 15 mg/day at randomization.

 -  Patients must have a history of being treated for at least 8 weeks with prednisone
 (≥10 mg/day or equivalent).

 -  Patient must have had at least one episode of unequivocal PMR flare while attempting
 to taper prednisone at a dose that is ≥7.5 mg/day (or equivalent) within the past 12
 Weeks prior to screening:

 -  Unequivocal symptoms of PMR flare include shoulder and/or hip girdle pain associated
 with inflammatory stiffness.

 -  Patients must have erythrocyte sedimentation rate ≥30 mm/hr and/or C-reactive protein
 ≥10 mg/L associated with PMR disease activity within 12 weeks prior to screening.

 Exclusion criteria:

 -  Diagnosis of giant cell arteritis (e.g., persistent or recurrent localized headache,
 temporal artery or scalp tenderness, jaw claudication, extremity claudication, blurry
 or loss of vision, symptoms of stroke).

 -  Diagnosis of active fibromyalgia.

 -  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 of rhabdomyolysis or neuropathic muscular diseases.

 -  Inadequately treated hypothyroidism.

 -  Organ transplant recipient.

 -  Therapeutic failure including inadequate response or intolerance, or contraindication,
 to biological IL-6 antagonist.

 -  Any prior (within the defined period below) or concurrent use of immunosuppressive
 therapies but not limited to any of the following:

 -  Janus kinase inhibitor within 4 weeks of baseline.

 -  Alkylating agents including cyclophosphamide within 6 months of baseline.

 -  Cell-depletion agents (e.g., anti CD20) without evidence of recovery of B cells to
 baseline level.

 -  Tumor necrosis factor inhibitors within 2-8 weeks (etanercept within 2 weeks,
 infliximab, certolizumab, golimumab, or adalimumab within 8 weeks), or after at least
 5 half-lives have elapsed, whichever is longer.

 -  Abatacept within 8 weeks of baseline.

 -  Anakinra within 1 week of baseline.

 -  Cyclosporine, azathioprine or mycophenolate mofetil or leflunomide within 4 weeks of
 baseline.

 -  Unstable methotrexate (MTX) dose and/or MTX dose >15mg/week within 3 months of
 baseline

 -  Concurrent use of systemic CS for conditions other than PMR.

 -  Pregnant or breastfeeding woman.

 -  Patients with active or untreated latent tuberculosis.

 -  Patients with history of invasive opportunistic infections.

 -  Patients with fever associated with infection or chronic, persistent or recurring
 infections requiring active treatment.

 -  Patients with uncontrolled diabetes mellitus.

 -  Patients with non-healed or healing skin ulcers.

 -  Patients who received any live, attenuated vaccine within 3 months of baseline.

 -  Patients who are positive for hepatitis B, hepatitis C and/or HIV.

 -  Patients with a history of active or recurrent herpes zoster.

 -  Patients with a history of or prior articular or prosthetic joint infection.

 -  Prior or current history of malignancy.

 -  Patients who have had surgery within 4 weeks of screening or planned surgery during
 study.

 -  Patients with a history of inflammatory bowel disease or severe diverticulitis or
 previous gastrointestinal perforation.

 The above information is not intended to contain all considerations relevant to a patient's
 potential participation in a clinical trial.