SIRIUS Sarcoidosis with moderate to severe facial skin involvement: an open multicenter study of the efficacy and safety of oral sirolimus

Start 23 Nov 2022 · Status Ongoing, recruitment ended · 1 EU/EEA countries · 5 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)

Status Ongoing, recruitment ended

Participants planned 10

Countries 1

Sites 5

Adult patients (men and women) (≥ 18 years of age) with cutaneous sarcoidosis involving the face

Evaluating the efficacy of sirolimus on facial skin involvement in sarcoidosis

Key facts

Sponsor: Assistance Publique Hopitaux De Paris
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Immune System Diseases [C20]
Trial duration: 23 Nov 2022 → ongoing
Decision date (initial): 2024-08-08
Transition trial: Yes
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes
Funding sources: DRCI-APHP

External identifiers

EU CT number: 2024-514609-76-00
EudraCT number: 2020-004359-34
ClinicalTrials.gov: NCT05458492

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluating the efficacy of sirolimus on facial skin involvement in sarcoidosis

Secondary objectives 7

1- Evaluate the significant efficacy of sirolimus on facial skin involvement in sarcoidosis
2- Evaluate complete remission of facial skin involvement in sarcoidosis
3- Assess the impact of sirolimus on quality of life in these patients
4- Evaluate photographic changes in facial lesions after 16 weeks of treatment
5- Study the efficacy of sirolimus on other sarcoidosis lesions 6- Evaluate the tolerability of sirolimus
6- Evaluate the tolerability of sirolimus
7- Evaluate proteomic and transcriptomic changes in circulating monocytes and skin after 16 weeks of sirolimus treatment

Conditions and MedDRA coding

Adult patients (men and women) (≥ 18 years of age) with cutaneous sarcoidosis involving the face

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

-Age ≥ 18 years < 75 years (men and wome
-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
Membership of a French health insurance scheme
- Patients who have failed at least one line of conventional systemic treatment, or who are naïve to systemic treatment.
- 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.
- Patients with written consent

Exclusion criteria 22

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

percentage of patients with a significant clinical response (relative decrease in SASI facial ≥ 25%) at 16 weeks of treatment

Secondary endpoints 10

1- Percentage of patients with a significant clinical response (relative reduction in facial SASI ≥ 50%) at 16 weeks of treatment
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))
2'- Percentage of patients with a complete or near-complete response according to skin PGA (PGA = 0 or 1).
3- Percentage of patients with improved dermatological quality of life (DLQI reduction > 25%) after 16 weeks of treatment (DLQI in appendix 2).
parison of front and profile photographs of the face with good luminosity between S0 and S16 (macroscopic assessment by the clinician).
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)
5'- Pulmonary sarcoidosis activity assessed by thoracic CT lung involvement (aCTAS score) at S16 or at study discharge
5''- Functional evaluation of pulmonary sarcoidosis assessed by respiratory function tests (vital capacity and gait perimeter) at S16 or at study discharge.
6- Collection of adverse events up to S16, in particular: mouth ulcers, drop in hemoglobin, leukocytes, platelets, infections, etc.
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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sirolimus

SUB10537MIG · Substance

Active substance: Sirolimus
Pharmaceutical form: COATED TABLET
Route of administration: ORAL USE
Max daily dose: 2 mg milligram(s)
Max total dose: 336 mg milligram(s)
Max treatment duration: 16 Week(s)
Authorisation status: Authorised
ATC code: - — -
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation: Assistance Publique Hopitaux De Paris
Address: Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux
City: Paris Cedex 10
Postcode: 75475
Country: France

Scientific contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Investigator

Public contact point

Organisation: Assistance Publique Hopitaux De Paris
Contact name: Investigator

Locations

1 EU/EEA country · 5 investigational sites

By country

Country	MS status	Planned subjects	Sites
France	Ongoing, recruitment ended	10	5
Rest of world	—	0	—