Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
Condition: Sarcoidosis
MeSH terms: Sarcoidosis
Intervention: Sarilumab; Placebo
Intervention description: Sarilumab 200 mg administered subcutaneously; Placebo administered subcutaneously
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: All subjects will all receive sarilumab 200 mg subcutaneously every two weeks for the first 16 weeks of the study. At Week 16, those patients who were able to successfully taper off of prednisone will then be assigned randomly to receive either sarilumab 200 mg subcutaneously every two weeks (study drug) or placebo subcutaneously for an additional 12 weeks.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Study doctor and personnel will not know whether you are assigned to the sarilumab group or the placebo group after Week 16.
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: glucocorticoid-dependent

Summary:

      The purpose of this study is to compare the effectiveness and the safety of sarilumab in
      patients with glucocorticoid-dependent sarcoidosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Biopsy proven non-caseating granulomas consistent with sarcoidosis

          -  negative infectious studies including AFB and fungal stains, and with compatible
             clinical and/or radiographic manifestations of sarcoidosis.

          -  Involvement of the lungs (stage II or III pulmonary sarcoidosis), lymph nodes, liver,
             kidneys, spleen, bone, soft tissues, skin, and/or eyes.

          -  At least one active manifestation, defined by the need for ongoing glucocorticoid
             treatment to control a sign or symptom of sarcoidosis, which requires treatment with
             prednisone (or equivalent corticosteroid) ≥ 10 mg and ≤ 60 mg daily (i.e.
             glucocorticoid dependence), with stable dosing for ≥ 28 days prior to baseline.

          -  patients taking a glucocorticoid other than prednisone, will be changed to prednisone
             at the equivalent dose and take this daily for ≥ 14 days prior to baseline.

          -  DMARDs including methotrexate, leflunomide, azathioprine, mycophenolate mofetil,
             and/or anti-malarials (i.e. hydroxychloroquine) permitted must be stable for ≥ 28 days
             prior to baseline and remain stable during follow-up.

        Exclusion Criteria:

          -  Stage IV pulmonary sarcoidosis.

          -  Central nervous system sarcoidosis.

          -  Cardiac sarcoidosis.

          -  Prior treatment with an anti-IL-6 therapy.

          -  Treatment with a biologic agent including rituximab, belimumab, TNF inhibitors,
             abatacept, or IL-17 inhibitors administered within 28 days prior to baseline (6 months
             for rituximab).

          -  Treatment with cyclophosphamide within 3 months prior to baseline.

          -  Treatment with prednisone < 10 mg or > 60 mg daily.

          -  Known hypersensitivity or allergy to the study drug.

          -  History of, or current, inflammatory or autoimmune disease other than sarcoidosis
             which would present a safety issue or confound interpretation of the data.

          -  Prior or current history of other significant concomitant illness that, according to
             the investigator's judgment, would adversely affect the patient's participation in the
             study. These include, but are not limited to, cardiovascular (including stage III or
             IV cardiac failure according to the New York Heart Association classification),
             neurological (including demyelinating disease), active infectious diseases, or history
             of diverticulitis or gastrointestinal perforation.

          -  Patients currently pregnant or breast-feeding.

          -  Women of childbearing potential (WOCBP) who are unwilling to utilize adequate
             contraception and unwilling to not become pregnant during the full course of the study
             (must be willing to be tested for pregnancy). Adequate contraceptive measures include
             oral contraceptives (continuous use, as per prescription, for 2 or more cycles prior
             to screening), intrauterine devices, contraceptive sponges, condoms or diaphragms plus
             foam, or jelly, or surgical procedures such as bilateral tubal ligation or vasectomy
             in partner.

          -  Administration of a live/attenuated vaccine within 30 days.

          -  Evidence of active tuberculosis, HIV, or hepatitis B or C infection.

          -  History of cancer other than non-melanoma skin cancer.

          -  Patients with any of the following laboratory abnormalities at the screening visit:
             hemoglobin <8.5 g/dL, white blood cells <3000/mm3, neutrophils <2000/mm3, platelet
             count <150,000 cells/mm3, aspartate aminotransferase (AST) or ALT >1.5 x ULN, and/or
             bilirubin (total) above the upper limit of normal (unless Gilbert's disease has been
             determined by genetic testing and documented).

          -  Presence of severe uncontrolled hypercholesterolemia (>350 mg/dL, 9.1 mmol/L) or
             hypertriglyceridemia (>500 mg/dL, 5.6 mmol/L) at screening or baseline.

          -  Patients with calculated creatinine clearance <30 mL/minute (using Cockroft-Gault
             formula).

          -  History of alcohol or drug abuse within 5 years prior to the screening visit.

          -  Participation in any clinical research study evaluating another investigational drug
             or therapy within 5 half-lives or 60 days of first investigational medicinal product
             (IMP) administration, whichever is longer.

          -  Any patient who has had surgery within 4 weeks prior to the screening visit or with
             planned surgery during the course of the study.