Sirolimus in Cutaneous Sarcoidosis

Официальное название

Cutaneous Sarcoidosis With Moderate to Severe Involvement of the Face : Multicenter Open-label Study of Oral Sirolimus Efficacy and Tolerance

Обзор

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.

Вмешательства

• Препарат Sirolimus
  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

Первичные конечные точки

• Percentage of patients with a significant clinical response [Срок оценки: at week 16]

Вторичные конечные точки (12)

• Percentage of patients with a good clinical response [Срок оценки: at week 16]
• Percentage of patients with complete clinical response [Срок оценки: at week 16]
• Percentage of patients with an improvement of their quality of dermatological life [Срок оценки: at week 16]
• Comparison of face facial photographs with good brightness compared to baseline [Срок оценки: at week 16]
• Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST) [Срок оценки: at week 16]
• Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST) [Срок оценки: at 12 months]
• Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score) [Срок оценки: at 16 weeks]
• Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score) [Срок оценки: at 12 months]
• Pulmonary Sarcoidosis activity [Срок оценки: at week 16]
• Pulmonary Sarcoidosis activity [Срок оценки: at 12 months]
• Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity [Срок оценки: at week 16]
• Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity [Срок оценки: at 12 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT05458492 · APHP180156

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗