Sirolimus in Cutaneous Sarcoidosis

NCT05458492 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: APHP180156
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Sarcoidosis; Cutaneous Sarcoidosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (19)

• Percentage of patients with a good clinical response

  at week 16

• Percentage of patients with complete clinical response

  at week 16

• Percentage of patients with an improvement of their quality of dermatological life

  at week 16

• 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 week 16

Study Arms (1)

Sirolimus Arm

EXPERIMENTAL

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

Drug: Sirolimus

Interventions

Sirolimus DRUG

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

Sirolimus Arm

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Intra-lesional corticotherapy for less than 3 months
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

MeSH Terms

Conditions

Sarcoidosis

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Central Study Contacts

Jean-David Bouaziz, Pr

CONTACT

+331 42 49 43 91; jean-david.bouaziz@aphp.fr

Matthieu Resche-Rigon

CONTACT

+33142499742; matthieu.resche-rigon@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2021
• First Posted: July 14, 2022
• Study Start: July 1, 2022
• Primary Completion: May 1, 2024
• Study Completion (Estimated): May 1, 2027
• Last Updated: July 14, 2022

Record last verified: 2022-07