Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
Study Details
Study Description
Brief Summary
The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The purpose of this study is to compare the effectivness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis. To demonstrate that sarilumab treatment will be effective for inducing and maintaining glucocorticoid-free remission in male or female patients with biopsy proven active, glucocorticoid-dependent sarcoidosis affecting the lungs, lymph nodes, liver, kidneys, spleen, bone, soft tissues, skin, and/or eyes.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Study drug sarilumab 200 mg subcutaneously every two weeks |
Drug: Sarilumab 200 MG/1.14 ML Subcutaneous Solution [KEVZARA]_#1
Sarilumab vs Placebo
|
| Placebo Comparator: placebo placebo subcutaneously every two weeks |
Drug: Placebos
Placebo
|
Outcome Measures
Primary Outcome Measures
- flare-free survival of sarilumab-treated patients compared to placebo-treated controls [2 weeks]
Patients will be considered to have flared if they receive rescue medication including increased glucocorticoids, or if they discontinue the study treatment in order to start a different therapy.
Secondary Outcome Measures
- Change in physician and patient assessments [2 weeks]
extrapulmonary physician organ severity tool (ePOST) Score Description: Slight Mild Moderate Moderate to severe Severe Very Severe
- change in FACIT-F score (fatigue scale [2 weeks]
FACIT-F score Scale: 0: Not at all A little Somewhat Ouite a bit Very much
- change in prednisone dose [2 weeks]
prednisone dose
- change in pulmonary function tests (FVC) [2 weeks]
pulmonary function test (FVC)
- change in ALT [2 weeks]
ALT
- change in serum creatinine [2 weeks]
Serum creatinine
- change in the Sarcoidosis Activity and Severity Index for cutaneous sarcoidosis [2 weeks]
Sarcoidosis Activity and Severity Index
- change in size of sarcoidosis lesions [2 weeks]
size of sarcoidosis lesions
- Change in Pulmonary Function (FEV1) [2 weeks]
FEV1
- change in AST [2 weeks]
AST
- Change in Urine Protein level [2 weeks]
Urine protein
- 68/66 Joint evaluation [2 weeks]
Joint evaluation Score: 0: Absent 1: Present 9: Not applicable
Eligibility Criteria
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.
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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).
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Treatment with cyclophosphamide within 3 months prior to baseline.
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Treatment with prednisone < 10 mg or > 60 mg daily.
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Known hypersensitivity or allergy to the study drug.
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History of, or current, inflammatory or autoimmune disease other than sarcoidosis which would present a safety issue or confound interpretation of the data.
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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.
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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.
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Administration of a live/attenuated vaccine within 30 days.
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Evidence of active tuberculosis, HIV, or hepatitis B or C infection.
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History of cancer other than non-melanoma skin cancer.
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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).
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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.
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Patients with calculated creatinine clearance <30 mL/minute (using Cockroft-Gault formula).
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History of alcohol or drug abuse within 5 years prior to the screening visit.
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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.
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Any patient who has had surgery within 4 weeks prior to the screening visit or with planned surgery during the course of the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Stanford University | Palo Alto | California | United States | 94304 |
Sponsors and Collaborators
- Stanford University
Investigators
- Principal Investigator: Mark Genovese, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 48375