Sirolimus in Cutaneous Sarcoidosis

Sarcoidosis Clinical Trial

— SIRIUS  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05458492
• Other study ID #: APHP180156
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 2022
• Est. completion date: May 2027

Study information

• Verified date: July 2022
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: Jean-David Bouaziz, Pr
• Phone: +331 42 49 43 91
• Email: jean-david.bouaziz[@]aphp.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 10
• Est. completion date: May 2027
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

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 ßHCG 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

Related Conditions & MeSH terms

• Cutaneous Sarcoidosis
• Sarcoidosis

Intervention

Drug:
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients with a significant clinical response	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.	at week 16
Secondary	Percentage of patients with a good clinical response	A good clinical response will be defined as a relative decrease of "facial SASI" = 50%.; 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.	at week 16
Secondary	Percentage of patients with complete clinical response	Complete clinical response will be defined as "facial SASI" = 0. 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.	at week 16
Secondary	Percentage of patients with an improvement of their quality of dermatological life	An improvement will be defined as a decrease of Dermatology Life Quality Index (DLQI) questionnaire> 25%. DLQI goes from 0 to 30. A lower score indicated a good quality of Life, and a higher score a worse quality of life.	at week 16
Secondary	Comparison of face facial photographs with good brightness compared to baseline	Qualitative clinical aspects of skin sarcoidosis lesions will be compared between baseline and Week 16, as an illustrative proof in addition to quantitative skin score assessment (Facial SASI)	at week 16
Secondary	Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)	Sarcoidosis activity for all organs will be evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST) (from 0 (normal) to 6(severe impairment))	at week 16
Secondary	Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)	Sarcoidosis activity for all organs will be evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST) (from 0 (normal) to 6(severe impairment))	at 12 months
Secondary	Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)	Sarcoidosis activity for all organs will be evaluted using Score Sarcoidosis disease activity index (SDAI score) : it goes from 0 to 167 (the higher the score, the greater the disease activity).	at 16 weeks
Secondary	Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)	Sarcoidosis activity for all organs will be evaluted using Score Sarcoidosis disease activity index (SDAI score) : it goes from 0 to 167 (the higher the score, the greater the disease activity).	at 12 months
Secondary	Pulmonary Sarcoidosis activity	Pulmonary Sarcoidosis activity will be assessed using Abbreviated CT score to quantify disease activity in pulmonary sarcoidosis (aCTAS score) to assess pulmonary involvement. It goes from 0 to 4 (the higher the score, the greater the pulmonary disease activity).	at week 16
Secondary	Pulmonary Sarcoidosis activity	Pulmonary Sarcoidosis activity will be assessed using Abbreviated CT score to quantify disease activity in pulmonary sarcoidosis (aCTAS score) to assess pulmonary involvement. It goes from 0 to 4 (the higher the score, the greater the pulmonary disease activity).	at 12 months
Secondary	Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity	Pulmonary sarcoidosis functionnal evaluation will be assessed using Functional respiratory explorations by vital capacity	at week 16
Secondary	Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity	Pulmonary sarcoidosis functionnal evaluation will be assessed using Functional respiratory explorations by vital capacity	at 12 months
Secondary	Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter	Pulmonary sarcoidosis functionnal evaluation will be assessed by walking perimeter (in meters)	at week 16
Secondary	Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter	Pulmonary sarcoidosis functionnal evaluation will be assessed by walking perimeter (in meters)	at 12 months
Secondary	Percentage of patients with adverse events		up to 16 weeks
Secondary	Evaluate CD68, phospho-mTOR and phospho-p70S6K expression on skin biopsies	Immunohistochemical assessment will be assessed using optical microscopy	at 16 weeks
Secondary	Transcriptomic analysis of skin	It will be assessed using microarray (Affymetrix)	at 16 weeks
Secondary	Circulating monocytes	It will be assessed using microarray (Affymetrix)	at 16 weeks
Secondary	Percentage of patients with a complete or near-complete response based on PGA (PGA = 0 or 1) of the skin.		at 16 weeks