SIROLIMUS for Cutaneous sarcoidosis

Inclusion criteria

• {"criterion_text":"-Age ≥ 18 years < 75 years (men and wome"}
• {"criterion_text":"-Cutaneous sarcoidosis with facial involvement (diagnosed as follows: compatible clinical appearance showing brownish or yellowish erythematoviolet macules or papules or nodules and compatible histological appearance on either facial or extrafacial skin biopsy confirming the diagnosis of sarcoidosis showing epithelioid and gigantocellular granulomas without caseous necrosis) moderate to severe defined by: SASI (sarcoidosis area and severity index) facial score ≥ 2 AND PGA (Physician's Global Assessment, scale 1 to 10) of skin ≥ 5"}
• {"criterion_text":"-Membership of a French health insurance scheme"}
• {"criterion_text":"- Patients who have failed at least one line of conventional systemic treatment, or who are naïve to systemic treatment."}
• {"criterion_text":"- For women of childbearing age (unless confirmed post-menopausal or sterile), pregnancy test with negative βHCG. Effective contraception by contraceptive pill or intrauterine device must be used during treatment with Sirolimus and for 12 weeks after discontinuation of sirolimus."}
• {"criterion_text":"- Patients with written consent"}

Exclusion criteria

• {"criterion_text":"-Severe hepatic impairment (cytolysis (ALT) > 3N and/or cholestasis (PAL) > 3N)"}
• {"criterion_text":"-Treatment with cyclins for less than 1 month"}
• {"criterion_text":"-Treatment with topical corticosteroids or tacrolimus for less than 1 week"}
• {"criterion_text":"-At least one organ affected by sarcoidosis requiring systemic treatment other than sirolimus (oral corticosteroid or systemic per os or parenteral immunosuppressive therapy)"}
• {"criterion_text":"-Cholesterolemia > 3 g/L or triglyceridemia > 4 g/L"}
• {"criterion_text":"-Concomitant administration of powerful CYP3A4 inhibitors or inducers such as rifampicin, ketoconazole, voriconazole, telithromcyine, diltiazem, verapamil, erythromycin, clarythromycin, ciclosporin."}
• {"criterion_text":"-Pregnancy or breast-feeding"}
• {"criterion_text":"-Active infection, including tuberculosis"}
• {"criterion_text":"-Uncontrolled hypertension (SBP > 150 mmHg and/or DBP > 100 mmHg)"}
• {"criterion_text":"- Patients under guardianship or trusteeship, persons deprived of their liberty, under court protection, under psychiatric care, under restraint, admitted to a health or social establishment for purposes other than those of research"}
• {"criterion_text":"-cancer patient (except basal cell carcinoma of the skin or cancer in situ of the uterine cervix)"}
• {"criterion_text":"-Allergy or intolerance to sirolimus or any of its excipients"}
• {"criterion_text":"-Risk of poor patient compliance."}
• {"criterion_text":"-Use of grapefruit or grapefruit juice during treatment"}
• {"criterion_text":"- patients with fructose or galactose intolerance, glucose-galactose malabsorption, sucrase-isomaltase or Lapp lactase deficiency."}
• {"criterion_text":"-Peanut or soy allergy"}
• {"criterion_text":"- Lung or liver transplant patients"}
• {"criterion_text":"-Treatment with general corticosteroids or immunosuppressive agents (methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine) in the month preceding inclusion."}
• {"criterion_text":"-Treatment with hydroxychloroquine in the month prior to inclusion"}
• {"criterion_text":"-Treatment with intralesional corticoids for less than 3 months"}
• {"criterion_text":"-Treatment with biotherapies (anti-TNFa, anti-IL12/23, anti-IL17A) in the 3 months prior to inclusion"}
• {"criterion_text":"-Treatment with thalidomide or other imides for less than 3 months"}

Primary endpoints

• {"endpoint_text":"-percentage of patients with a significant clinical response (relative decrease in SASI facial ≥ 25%) at 16 weeks of treatment","definition_or_measurement_approach":"Relative decrease in facial SASI (sarcoidosis area and severity index) ≥ 25% measured at 16 weeks of treatment."}

Secondary endpoints

• {"endpoint_text":"-1- Percentage of patients with a significant clinical response (relative reduction in facial SASI ≥ 50%) at 16 weeks of treatment","definition_or_measurement_approach":"Relative reduction in facial SASI ≥ 50% measured at 16 weeks of treatment."}
• {"endpoint_text":"-2- Percentage of patients with a complete clinical response (\"SASI facial\" = 0) at 16 weeks of treatment (SASI facial clinical assessment at screening, inclusion and closing visit (S16))","definition_or_measurement_approach":"Proportion with facial SASI = 0 at 16 weeks; assessments at screening, inclusion and S16 (closing visit)."}
• {"endpoint_text":"-2'- Percentage of patients with a complete or near-complete response according to skin PGA (PGA = 0 or 1).","definition_or_measurement_approach":"Skin Physician's Global Assessment (PGA) with response defined as PGA = 0 or 1."}
• {"endpoint_text":"-3- Percentage of patients with improved dermatological quality of life (DLQI reduction > 25%) after 16 weeks of treatment (DLQI in appendix 2).","definition_or_measurement_approach":"Dermatology Life Quality Index (DLQI) assessed; improvement defined as >25% reduction at 16 weeks."}
• {"endpoint_text":"-parison of front and profile photographs of the face with good luminosity between S0 and S16 (macroscopic assessment by the clinician).","definition_or_measurement_approach":"Macroscopic clinical photographic comparison (front and profile) between baseline (S0) and week 16 (S16)."}
• {"endpoint_text":"-5- Sarcoidosis activity score assessed for all organs by ePOST (extra-pulmonary organ severity score from 0 to 6) + SDAI score at S16 or at study discharge (compared with inclusion)","definition_or_measurement_approach":"ePOST extra-pulmonary organ severity score (0-6) and SDAI score compared at S16 or at study discharge versus inclusion."}
• {"endpoint_text":"-5'- Pulmonary sarcoidosis activity assessed by thoracic CT lung involvement (aCTAS score) at S16 or at study discharge","definition_or_measurement_approach":"Thoracic CT assessment using aCTAS score at S16 or study discharge."}
• {"endpoint_text":"-5''- Functional evaluation of pulmonary sarcoidosis assessed by respiratory function tests (vital capacity and gait perimeter) at S16 or at study discharge.","definition_or_measurement_approach":"Respiratory function tests (vital capacity) and 6-minute walk/gait perimeter assessed at S16 or study discharge."}
• {"endpoint_text":"-6- Collection of adverse events up to S16, in particular: mouth ulcers, drop in hemoglobin, leukocytes, platelets, infections, etc.","definition_or_measurement_approach":"Safety: systematic collection of adverse events through S16, specific monitoring of mucosal ulcers, hematological changes, infections, etc."}
• {"endpoint_text":"-7- Evaluate CD68, phospho-mTOR and phospho-p70S6K labeling on skin biopsies and expression of coding mRNA transcripts by microarray (Affymetrix) in skin and circulating monocytes.","definition_or_measurement_approach":"Immunohistochemical labeling (CD68, phospho-mTOR, phospho-p70S6K) on skin biopsies and transcriptomic analysis by Affymetrix microarray in skin and circulating monocytes."}

France

Earliest CTIS Part Ii Submission Date

28-06-2024

Latest Decision Or Authorization Date

15-09-2025

Processing Time Days

444

Number Of Sites

5

Number Of Participants

10

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France