Cutaneous Sarcoidosis With Moderate to Severe Involvement of the Face : Multicenter Open-label Study of Oral Sirolimus Efficacy and Tolerance
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 10
- 主要终点
- Percentage of patients with a significant clinical response
研究概览
简要总结
Sarcoidosis is a multisystemic disease of unknown etiology characterized by the presence of epithelioid granulomas without caseous necrosis in the organs involved. Sarcoidosis cutaneous lesions can be severe. There is no recommendation for the treatment of cutaneous sarcoidosis. A recent study highlights the potential efficacy of mTOR inhibitors in the treatment of sarcoidosis granulomas. The hypothesis is that sirolimus could be effective for sarcoidosis treatment, especially for cutaneous lesions.
The main objective of this study is to evaluate sirolimus efficacy on cutaneous sarcoidosis of the face.
The main evaluation criteria is the percentage of patients with a significant clinical response (relative decrease in "facial SASI" ≥ 25%) at week 16 of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old <75 years old (men and women)
- •Cutaneous sarcoidosis of the face (diagnosed according to the following criteria : compatible clinical appearance showing erythemato-purple, brownish or yellowish macules or papules or nodules and compatible histological appearance with a facial or extra facial skin biopsy confirming the diagnosis of sarcoidosis showing epithelioid and giganto-cellular granuloma without caseous necrosis) moderate to severe defined by: "Facial SASI" Score (Sarcoidosis Area and Severity Index) ≥ 2 and PGA (Physician's Global Assessment,0 to 10 scale) ≥ 5
- •Health insurance plan coverage
- •Patients who never had a systemic treatment or who had at least one classical systemic treatment failure for sarcoidosis treatment
- •For women of childbearing age (unless post-menopausal or sterile), pregnancy test with βHCG negative. Effective contraception should be used during sirolimus treatment and for 12 weeks after stopping sirolimus
- •Patients who have signed a written consent
排除标准
- •Severe hepatic failure (Cytolysis (ALAT)> 3N and / or Cholestase (PAL)> 3N)
- •Allergy or intolerance to sirolimus or at one of its excipients
- •Allergy to peanut or soybeans
- •Patient with a pulmonary or hepatic graft
- •General corticotherapy or immunosuppressive treatment (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, ciclosporin) in the month before the inclusion
- •Intra-lesional corticotherapy for less than 3 months
- •Biotherapy (anti-TNFa, anti-IL12/23, anti-IL17A) within 3 months preceding the inclusion
- •Thalidomide or other -imide treatment for less than 3 months
- •Cyclins treatment for less than 1 month
- •Topical corticosteroids or topical tacrolimus for less than 1 week
- •Sarcoidosis involvement of at least one organ requiring systemic treatment other than sirolimus (oral corticosteroid or systemic immunosuppressive treatment)
- •Cholesterolemia> 300 mg/ dl or triglyceridemia> 400 mg/dl
- •Administration of strong CYP3A4 inhibitors or inducers such as rifampicin, ketoconazole, voriconazole, telithromycin , diltiazem, verapamil, erythromycin, clarythromycin, ciclosporin
- •Pregnancy or breastfeeding
- •Active infection including tuberculosis disease
- •Non-controlled arterial hypertension (TAS> 150 mmHg and / or TAD> 100 mmHg)
- •Patient under guardianship or curatorship, patients deprived of freedom, under safeguarding of justice, receiving psychiatric care, under the constraint, admitted in a health or social institution for purposes other than those of research
- •Patient with cancer (except cutaneous basal cell carcinoma or in situ cervical cancer)
- •Risk of patient bad compliance
- •Grapefruit or grapefruit juice consumption during the treatment duration
- •Patients with fructose intolerance, galactose intolerance, glucose-galactose malabsorption, insufficiency in sucrase-isomaltase or Lapp lactase
研究组 & 干预措施
Sirolimus Arm
Sirolimus, tablets 2 mg/day with dose adjustment of 1 to 3 mg/day for residual concentrations between 4 and 10 ng/mL
1 dose daily for 16 weeks
干预措施: Sirolimus (Drug)
结局指标
主要结局
Percentage of patients with a significant clinical response
时间窗: at week 16
Significant clinical response will be defined as a relative decrease in "facial SASI" ≥ 25% compared to baseline. Facial SASI score evaluates 4 features for each of 4 facial quadrants and the nose: erythema, induration, and desquamation, each ranging from 0 (none) to 4 (very severe), and an area score ranging from 0 (0%) to 6 (90-100%). The maximal range of modified Facial SASI scores is 0 to 72.
次要结局
- Percentage of patients with an improvement of their quality of dermatological life(at week 16)
- Percentage of patients with a good clinical response(at week 16)
- Percentage of patients with complete clinical response(at week 16)
- Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)(at 12 months)
- Comparison of face facial photographs with good brightness compared to baseline(at week 16)
- Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)(at 12 months)
- Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter(at 12 months)
- Percentage of patients with adverse events(up to 16 weeks)
- Evaluate CD68, phospho-mTOR and phospho-p70S6K expression on skin biopsies(at 16 weeks)
- Pulmonary Sarcoidosis activity(at 12 months)
- Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity(at 12 months)
- Transcriptomic analysis of skin(at 16 weeks)
- Circulating monocytes(at 16 weeks)
- Percentage of patients with a complete or near-complete response based on PGA (PGA = 0 or 1) of the skin.(at 16 weeks)