NCT04008069已完成2 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants Without Sarcoidosis Flare (Flare-Free Survival)
研究概览
简要总结
The purpose of this study is to compare the effectiveness and the safety of sarilumab in patients with glucocorticoid-dependent sarcoidosis.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Study doctor and personnel will not know whether you are assigned to the sarilumab group or the placebo group after Week 16.
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Open-Label Sarilumab (pre-randomization)
Experimental
On entering the study, all participants receive open-label sarilumab every two weeks for 16 weeks.
干预措施: Sarilumab (Drug)
Double-Blind Sarilumab (post-randomization)
Experimental
After completing the open-label period, participants are randomized in blinded fashion to receive sarilumab every two weeks for 12 weeks.
干预措施: Sarilumab (Drug)
Double-Blind Placebo (post-randomization)
Placebo Comparator
After completing the open-label period, participants are randomized in blinded fashion to receive placebo every two weeks for 12 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants Without Sarcoidosis Flare (Flare-Free Survival)
时间窗: Week 16 to Week 28
The primary outcome was flare-free survival of sarilumab-treated patients compared to placebo-treated controls. 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.
次要结局
- Change in Pulmonary Function (FEV1) Percent Predicted(Baseline and week 16)
- Change From Baseline in Physician Disease Activity Visual Analogue Scale (VAS)(Baseline, week 16, and week 28)
- Number of Tender and Swollen Joints Per 68/66 Joint Evaluation(Baseline, week 16, and week 28)
- Sarcoidosis Activity and Severity Index for Cutaneous Sarcoidosis(Baseline, week 16, and week 28)
- Change From Baseline in Serum Angiotensin Converting Enzyme(Baseline, week 16, and week 28)
- Number of Participants With Serum Creatinine Outside Normal Range(Baseline, week 16, and week 28)
- Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted(Baseline and week 16)
- Change in Size of Sarcoidosis Lesions(Baseline, week 16, and week 28)
- Change From Baseline in Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted(Baseline, and week 16)
- Change From Baseline in Extrapulmonary Physician Organ Severity Tool (ePOST) Scale Score(Baseline, week 16, and week 28)
- Change From Baseline in Patient Disease Activity Visual Analogue Scale (VAS)(Baseline, week 16, and week 28)
- Change From Baseline in FACIT-F Score (Fatigue Scale)(Baseline, week 16, and week 28)
- Change From Baseline in Serum C-Reactive Protein (CRP)(Baseline, week 16, and week 28)
- Change in Prednisone Dose(Baseline, week 16, and week 28)
- Change From Baseline in Erythrocyte Sedimentation Rate (ESR)(Baseline, week 16, and week 28)
- Number of Participants With Alanine Aminotransferase (ALT) Outside Normal Range(Baseline, week 16, and week 28)
- Number of Participants With Urine Protein Outside Normal Range(Baseline, week 16, and week 28)
- Number of Participants With Aspartate Aminotransferase (AST) Outside Normal Range(Baseline, week 16, and week 28)
研究者
Matthew C. Baker
Clinical Assistant Professor
Stanford University
研究点 (1)
Loading locations...
相似试验
已完成
2 期
Evaluation of the Efficacy and Safety of Sarilumab in Hospitalized Patients With COVID-19COVID-19NCT04315298Regeneron Pharmaceuticals1,912
已完成
3 期
Efficacy and Safety of Sarilumab and Adalimumab Monotherapy in Patients With Rheumatoid Arthritis (SARIL-RA-MONARCH)Rheumatoid ArthritisNCT02332590Sanofi369
进行中（未招募）
3 期
A Study to Evaluate the Efficacy, Safety, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Satralizumab in Participants With Anti-N-methyl-D-aspartic Acid Receptor (NMDAR) or Anti-leucine-rich Glioma-inactivated 1 (LGI1) EncephalitisNCT05503264Hoffmann-La Roche122
已完成
3 期
Sarilumab COVID-19Corona Virus InfectionNCT04327388Sanofi420
已完成
2 期
A Study to Evaluate the Efficacy and Safety of Sirukumab in Confirmed Severe or Critical Confirmed Coronavirus Disease (COVID)-19Critical Confirmed Coronavirus Disease (COVID)-19NCT04380961Janssen Pharmaceutica N.V., Belgium212