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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03600818
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : March 20, 2020
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sanofi

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Polymyalgia Rheumatica Drug: Sarilumab SAR153191 (REGN88) Drug: Sarilumab-matching placebo Drug: Prednisone Drug: Prednisone-matching placebo Phase 3

Detailed Description:
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Sarilumab in Patients With Polymyalgia Rheumatica
Actual Study Start Date : October 9, 2018
Estimated Primary Completion Date : December 2022
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Group 1
Sarilumab once every 2 weeks plus prednisone taper regimen of 14 weeks
Drug: Sarilumab SAR153191 (REGN88)
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Drug: Prednisone
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Drug: Prednisone-matching placebo
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Drug: Prednisone
Pharmaceutical form:tablets Route of administration: oral administration

Placebo Comparator: Group 2
Placebo matching sarilumab once every 2 weeks plus prednisone taper regimen of 52 weeks
Drug: Sarilumab-matching placebo
Pharmaceutical form:solution for injection Route of administration: subcutaneous

Drug: Prednisone
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Drug: Prednisone-matching placebo
Pharmaceutical form:over-encapsulated tablets Route of administration: oral administration

Drug: Prednisone
Pharmaceutical form:tablets Route of administration: oral administration




Primary Outcome Measures :
  1. Proportion of patients with sustained remission [ Time Frame: At Week 52 ]
    Proportion of patients achieving sustained remission at Week 52.


Secondary Outcome Measures :
  1. Components of sustained remission (composite measure) [ Time Frame: At Week 52 ]
    Summary of the components of sustained remission composite measure at Week 52.

  2. Cumulative corticosteroid dose [ Time Frame: Up to Week 52 ]
    Total cumulative corticosteroid (including prednisone) dose over 52 weeks.

  3. Time to first polymyalgia rheumatica (PMR) flare [ Time Frame: Up to Week 52 ]
    Duration of first PMR flare from clinical remission up to Week 52.

  4. Change in glucocorticoid toxicity index [ Time Frame: Up to Week 52 ]
    Changes from baseline in the glucocorticoid toxicity index and its components up to Week 52.

  5. Adverse events [ Time Frame: Up to Week 58 ]
    Number of adverse events.

  6. Pharmacokinetic [ Time Frame: Up to Week 58 ]
    Serum concentrations of sarilumab.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03600818


Contacts
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Contact: Trial Transparency email recommended (Toll free number for US & Canada) 800-633-1610 ext 1 then # Contact-US@sanofi.com

Locations
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Sponsors and Collaborators
Sanofi
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Sciences & Operations Sanofi

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03600818    
Other Study ID Numbers: EFC15160
2017-002989-42 ( EudraCT Number )
U1111-1201-0777 ( Other Identifier: UTN )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polymyalgia Rheumatica
Giant Cell Arteritis
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Vasculitis, Central Nervous System
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Arteritis
Vasculitis
Skin Diseases, Vascular
Skin Diseases
Autoimmune Diseases
Immune System Diseases
Prednisone
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents