Cutaneous microcystic lymphatic malformations (CMLM) in children and adults MedDRA version: 20.0 Level: LLT Classification code 10003229 Term: Arteriovenous malformations System Organ Class: 100000004850
Conditions
Interventions
Product Name: Sirolimus 0,1% crème
Pharmaceutical Form: Cream
INN or Proposed INN: SIROLIMUS
CAS Number: 53123-88-9
Concentration unit:
Sponsors
CHRU TOURS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients = 6 years - Updated immunization schedule - Diagnosis of primary cutaneous microcystic lymphatic malformation (CMLM) confirmed by histopathological or dermoscopic examination, with or without an underlying malformation or a syndromic malformation (Protée syndrome for instance), responsible for impairment (oozing, bleeding and/or pain) - CMLM = 20 cm2, that can be divided into 2 parts of similar severity - Informed, written consent of the subject and his/her parents if =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Patients with lymphatic malformation requiring a continued backround therapy (involving deep organs) - Secondary lymphatic malformations (lymphangiectasia post-radiotherapy, etc) - Previous treatment with oral or topical mTOR inhibitors within 12 months before inclusion - Previous treatment with oral or topical steroids within 10 days before inclusion - Immunosuppression (immunosuppressive disease or immunosuppressive treatment) - Ongoing neoplasia - Active chronic infectious disease (HBV, HCV, HIV, etc) - Local fungal, viral (HSV, VZV, etc) or bacterial infection on the site of the CMLM (based on clinical examination) - Skin necrosis - Known allergy to one of the components of the topical sirolimus preparation or vehicle - Women of child-bearing potential (including teenagers) not using a reliable contraceptive method until the end of the study - Pregnant or breastfeeding women - Subject already involved in another therapeutic trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of a 12-week application period of 0.1% topical sirolimus in cutaneous microcystic lymphatic malformation in children and adults, versus topical vehicle.; Secondary Objective: To evaluate the efficacy of a 6-week application period of 0.1% topical sirolimus, versus topical vehicle, and of a 12-week, 20-week application period : - by comparing times W0 and W12 on photographs - regarding each of the following complications of the CMLM at W12 and W20 - by assessing the global self-reported efficacy of topical sirolimus vs vehicle at W12 and W20 - by assessing the global efficacy by the physician at W12 and W20 - by assessing functional and esthetic impairments at W20 - by evaluating pain linked to the CMLM at W20 - by evaluating a the effect on quality of life To measure systemic passage of sirolimus at W12 and W20 To evaluate tolerance of 0.1% topical sirolimus at W12 and W20 To measure the long-term efficacy by the investigator and the patient at M12 ;Primary end point(s): The primary outcome will consist in the PGA score (Physician Global Assessment) assessed by the investigator physician (blinded from the treatment). PGA score ranges from 0 (clear) to 5 (severe lesions), and is commonly used in several dermatologic conditions. For each patient, PGA of the area treated with the intervention (0.1% topical sirolimus) will be compared to PGA of the area treated with topical vehicle (inactive comparator).;Timepoint(s) of evaluation of this end point: At week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy by PGA score - Efficacy by two independent experts on the basis of standardized photographs (instructions will be given for standardizing photographs) on each area of the CMLM. The experts will have to identify, at the end of the study, which area among both received the active treatment. In case of disagreement, a consensus will be reached between both experts; if consensus is not reached, a third expert will be sought for final decision - Efficacy by the investigator blinded to treatment regarding severity of oozing, bleeding, erythema, and thickness on both areas (treated with topical sirolimus and topical vehicle), with a visual analog scale (VAS) from 0 to 10 - Self-assessment by the subject (and parents in case of children under 16) of the global improvement of CMLM in both areas using a VAS from 0 to 10 - Self-assessment of functional and esthetic impairments (by the patient and parents if patient < 16, using a 0 to 10 VAS) - Self-assessment of pain by the patient on a 0 to 10 VAS linked to the CMLM (a VAS adapted to children will be used for subjects under 16 years) - Self-assessment of quality of life using the validated DLQI scale (Dermatology Life Quality Index), or Child-DLQI for children - Evaluation of systemic passage of sirolimus - Tolerance of topical sirolimus: record of local side effects in both areas treated with topical sirolimus and vehicle ; record of general side effects - Biological safety (we will perform biological measurements that are required for assessing safety of oral sirolimus: blood cell count, liver and renal functions, ionogram, lipids [cholesterol and triglycerides] and glycemia) ; Timepoint(s) of evaluation of this end point: - PGA at baseline, W6, W20 and M12 - Photographs at baseline and W12 | — |
Countries
France
Contacts
Public ContactARC DRCI - Estelle BOIVIN
CHRU TOURS
Outcome results
None listed