Clinical trial NCT05458492: Sirolimus in Cutaneous Sarcoidosis
Official title: Cutaneous Sarcoidosis With Moderate to Severe Involvement of the Face : Multicenter Open-label Study of Oral Sirolimus Efficacy and Tolerance
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Sarcoidosis
Cutaneous Sarcoidosis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-07-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of patients with a significant clinical response
timeFrame: at week 16
Secondary outcomes:
measure: Percentage of patients with a good clinical response
timeFrame: at week 16
measure: Percentage of patients with complete clinical response
timeFrame: at week 16
measure: Percentage of patients with an improvement of their quality of dermatological life
timeFrame: at week 16
measure: Comparison of face facial photographs with good brightness compared to baseline
timeFrame: at week 16
measure: Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)
timeFrame: at week 16
measure: Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)
timeFrame: at 12 months
measure: Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)
timeFrame: at 16 weeks
measure: Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)
timeFrame: at 12 months
measure: Pulmonary Sarcoidosis activity
timeFrame: at week 16
measure: Pulmonary Sarcoidosis activity
timeFrame: at 12 months
measure: Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity
timeFrame: at week 16
measure: Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity
timeFrame: at 12 months
measure: Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
timeFrame: at week 16
measure: Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
timeFrame: at 12 months
measure: Percentage of patients with adverse events
timeFrame: up to 16 weeks
measure: Evaluate CD68, phospho-mTOR and phospho-p70S6K expression on skin biopsies
timeFrame: at 16 weeks
measure: Transcriptomic analysis of skin
timeFrame: at 16 weeks
measure: Circulating monocytes
timeFrame: at 16 weeks
measure: Percentage of patients with a complete or near-complete response based on PGA (PGA = 0 or 1) of the skin.
timeFrame: at 16 weeks
Other outcomes:
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