SarcoidosisPhase 2SIRIUSNCT05458492
Sirolimus in Cutaneous Sarcoidosis
A Phase 2 study testing Sirolimus in people with Sarcoidosis and Cutaneous Sarcoidosis, run by Assistance Publique - Hôpitaux de Paris.
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. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Sarcoidosis, Cutaneous Sarcoidosis
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- No sites listed yet
- Study dates
- Jul 2022to May 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Cutaneous Sarcoidosis With Moderate to Severe Involvement of the Face : Multicenter Open-label Study of Oral Sirolimus Efficacy and Tolerance
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
- Being tested
- Sirolimus
- Medical subject headings
- Sarcoidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: at week 16
Secondary outcomes (19)
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.
Measured: at week 16
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.
Measured: at week 16
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.
Measured: at week 16
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)
Measured: at week 16
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))
Measured: at week 16
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))
Measured: at 12 months
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).
Measured: at 16 weeks
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).
Measured: at 12 months
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).
Measured: at week 16
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).
Measured: at 12 months
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
Measured: at week 16
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
Measured: at 12 months
Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
Pulmonary sarcoidosis functionnal evaluation will be assessed by walking perimeter (in meters)
Measured: at week 16
Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
Pulmonary sarcoidosis functionnal evaluation will be assessed by walking perimeter (in meters)
Measured: at 12 months
Percentage of patients with adverse events
Measured: up to 16 weeks
Evaluate CD68, phospho-mTOR and phospho-p70S6K expression on skin biopsies
Immunohistochemical assessment will be assessed using optical microscopy
Measured: at 16 weeks
Transcriptomic analysis of skin
It will be assessed using microarray (Affymetrix)
Measured: at 16 weeks
Circulating monocytes
It will be assessed using microarray (Affymetrix)
Measured: at 16 weeks
Percentage of patients with a complete or near-complete response based on PGA (PGA = 0 or 1) of the skin.
Measured: at 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2022
- Study startJul 2022 (estimated)
- Primary completionMay 2024 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SarcoidosisStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05458492
- Sponsor's protocol ID
- APHP180156
- Acronym
- SIRIUS
- Status last verified
- Jul 2022
- First submitted
- 11 Oct 2021
- Last updated
- 14 Jul 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cutaneous Sarcoidosis With Moderate to Severe Involvement of the Face : Multicenter Open-label Study of Oral Sirolimus Efficacy and Tolerance
- ClinicalTrials.gov ID
- NCT05458492
- Acronym / sponsor ID
- SIRIUS / APHP180156
- Conditions
- Sarcoidosis, Cutaneous Sarcoidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jul 2022 (estimated)
- Primary completion
- May 2024 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 14 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus Arm | Experimental | Drug: SirolimusSirolimus, 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 |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusSirolimus, 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 Arm |
Primary outcome
Percentage of patients with a significant clinical response
Time frame: at week 16
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.
19 secondary outcomes
Percentage of patients with a good clinical response
Time frame: at week 16
Percentage of patients with complete clinical response
Time frame: at week 16
Percentage of patients with an improvement of their quality of dermatological life
Time frame: at week 16
Comparison of face facial photographs with good brightness compared to baseline
Time frame: at week 16
Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)
Time frame: at week 16
Sarcoidosis activity score evaluated for other organs evaluted using Extra-Pulmonary Physician Organ Severity Tool (ePOST)
Time frame: at 12 months
Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)
Time frame: at 16 weeks
Sarcoidosis activity score evaluated for other organs using Score Sarcoidosis disease activity index (SDAI score)
Time frame: at 12 months
Pulmonary Sarcoidosis activity
Time frame: at week 16
Pulmonary Sarcoidosis activity
Time frame: at 12 months
Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity
Time frame: at week 16
Pulmonary sarcoidosis functionnal evaluation assessed using Functional respiratory explorations by vital capacity
Time frame: at 12 months
Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
Time frame: at week 16
Pulmonary sarcoidosis functionnal evaluation assessed by walking perimeter
Time frame: at 12 months
Percentage of patients with adverse events
Time frame: up to 16 weeks
Evaluate CD68, phospho-mTOR and phospho-p70S6K expression on skin biopsies
Time frame: at 16 weeks
Transcriptomic analysis of skin
Time frame: at 16 weeks
Circulating monocytes
Time frame: at 16 weeks
Percentage of patients with a complete or near-complete response based on PGA (PGA = 0 or 1) of the skin.
Time frame: at 16 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2022.
- Individual participant dataSharing planned: Undecided
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A Study of Brepocitinib in Adults With Cutaneous Sarcoidosis
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus in people with Sarcoidosis and Cutaneous Sarcoidosis, run by Assistance Publique - Hôpitaux de Paris.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-David Bouaziz, Pr (+331 42 49 43 91, jean-david.bouaziz@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of patients with a significant clinical response (time frame: at week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jul 2022.