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

Sanofi

Status and phase: Terminated; Phase 3

Conditions: Polymyalgia Rheumatica

Treatments: Drug: Sarilumab-matching placebo; Drug: Prednisone; Drug: Prednisone-matching placebo; Drug: Sarilumab SAR153191 (REGN88)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03600818

EFC15160

2017-002989-42 (EudraCT Number)

U1111-1201-0777 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To evaluate the efficacy of KEVZARA (sarilumab) in participants with polymyalgia rheumatica (PMR) as assessed by the proportion of participants 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 participants with PMR 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 participants with PMR.
• To measure sarilumab serum concentrations in participants with PMR.
• To assess the effect of sarilumab in reducing glucocorticoid toxicity as measured by the composite glucocorticoid toxicity index (GTI) questionnaire.

Full description

Study duration per participant was approximative 62 weeks including up to a 4-week screening period, 52-week treatment period and 6-week follow-up period.

Enrollment: 118 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

• Diagnosis of PMR according to European League Against Rheumatism/American College of Rheumatology classification criteria.

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

• Participant was willing and able to take prednisone of 15 mg/day at randomization.

• Participants had a history of being treated for at least 8 weeks with prednisone (greater than or equal to [>=]10 mg/day or equivalent).

• Participants must have had at least one episode of unequivocal PMR flare while attempting to taper prednisone at a dose that was >= 7.5 mg/day (or equivalent) within the past 12 Weeks prior to screening:

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

• Participants had erythrocyte sedimentation rate >=30 millimeters per hour (mm/hr) and/or C-reactive protein >=10 milligrams per liter (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 interleukin-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 was 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 greater than (>) 15 mg/week within 3 months of Baseline

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

• Pregnant or breastfeeding woman.

• Participants with active or untreated latent tuberculosis.

• Participants with history of invasive opportunistic infections.

• Participants with fever associated with infection or chronic, persistent or recurring infections required active treatment.

• Participants with uncontrolled diabetes mellitus.

• Participants with non-healed or healing skin ulcers.

• Participants who received any live, attenuated vaccine within 3 months of Baseline.

• Participants who were positive for hepatitis B, hepatitis C and/or human immunodeficiency virus.

• Participants with a history of active or recurrent herpes zoster.

• Participants with a history of or prior articular or prosthetic joint infection.

• Prior or current history of malignancy.

• Participants who have had surgery within 4 weeks of screening or planned surgery during study.

• Participants with a history of inflammatory bowel disease or severe diverticulitis or previous gastrointestinal perforation.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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118 participants in 2 patient groups, including a placebo group

Placebo+52 Week Taper

Placebo Comparator group

Description:

Participants received sarilumab-matching placebo as subcutaneous (SC) injection every 2 weeks (q2w) up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone/prednisone-matching placebo tapering oral daily doses for 52 weeks.

Treatment:

Drug: Prednisone-matching placebo

Drug: Prednisone

Drug: Sarilumab-matching placebo

Drug: Prednisone

Sarilumab 200mg q2w+14 Week Taper

Experimental group

Description:

Participants received sarilumab 200 milligrams (mg) as SC injection q2w up to 52 weeks along with the combination of prednisone and/or prednisone-matching placebo according to the protocol-defined schedule. Participants received prednisone tapering oral daily doses during the first 14 weeks and prednisone-matching placebo from Week 14 up to Week 52.

Treatment:

Drug: Prednisone-matching placebo

Drug: Prednisone

Drug: Prednisone

Drug: Sarilumab SAR153191 (REGN88)