Clinical trial NCT04008069: Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
Official title: A Phase II, Single-Site, Double-Blind, Placebo-Controlled Randomized Withdrawal Study Assessing the Efficacy and Safety of Sarilumab in Patients With Glucocorticoid-Dependent Sarcoidosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Sarcoidosis
Keywords: glucocorticoid-dependent
Lead sponsor: Stanford University
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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

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.

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.

Primary outcomes:
measure: Number of Participants Without Sarcoidosis Flare (Flare-Free Survival)
timeFrame: Week 16 to Week 28
Secondary outcomes:
measure: Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted
timeFrame: Baseline and week 16
measure: Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted
timeFrame: Baseline, and week 16
measure: Change in Pulmonary Function (FEV1) Percent Predicted
timeFrame: Baseline and week 16
measure: Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS)
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS)
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in FACIT-F Score (Fatigue Scale)
timeFrame: Baseline, week 16, and week 28
measure: Number of Tender and Swollen Joints Per 68/66 Joint Evaluation
timeFrame: Baseline, week 16, and week 28
measure: Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis
timeFrame: Baseline, week 16, and week 28
measure: Change in Size of Sarcoidosis Lesions
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in Serum Angiotensin Converting Enzyme
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in Serum C-Reactive Protein (CRP)
timeFrame: Baseline, week 16, and week 28
measure: Change From Baseline in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline, week 16, and week 28
measure: Change in Prednisone Dose
timeFrame: Baseline, week 16, and week 28
measure: Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range
timeFrame: Baseline, week 16, and week 28
measure: Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range
timeFrame: Baseline, week 16, and week 28
measure: Number of Participants With Serum Creatinine Outside Normal Range
timeFrame: Baseline, week 16, and week 28
measure: Number of Participants With Urine Protein Outside Normal Range
timeFrame: Baseline, week 16, and week 28
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Matthew Baker, MD
role: PRINCIPAL_INVESTIGATOR
References: