Port Wine Stains
Conditions
Keywords
sirolimus, rapamycin, adjunct therapy, proof of concept, phase 2, dose ranging
Brief summary
The goal of this clinical trial is to learn if the use of rapamycin cream can be used as a treatment together with pulsed dyed laser in treating port wine stain birthmarks. The main question it aims to answer is: Will rapamycin cream and laser treatment show a greater improvement in appearance of port wine birthmarks, compared to treatment with placebo cream and laser? Researchers will compare two concentrations of rapamycin cream (0.6% or 1.0%) with placebo treatment to see if appearance is improved following 12 weeks of treatment. Participants will receive laser treatment of their port wine birthmark and then apply the rapamycin or placebo cream daily for 12 weeks. Patients will visit the clinic every 4 weeks for checkups and tests.
Detailed description
This is a single-centre, double-blind, randomized withdrawal design, parallel group, placebo-controlled, dose-response clinical study investigating the efficacy and safety of two concentrations of topical rapamycin cream in the treatment of port wine stain as an adjunct to pulsed dyed laser (PDL) in paediatric patients. 30 participants will be enrolled into the study. The study hypothesis is that topical rapamycin, as an adjunct to PDL, will show a dose-dependent increase in the blanching of port wine birthmarks, compared to PDL with placebo after 12 weeks. Eligible participants will undergo PDL treatment of their entire port wine birthmark. Patients that respond positively to PDL within 5 days will be enrolled and randomized, before the first application of the study drug. Participants will be randomly assigned to one of three possible treatments in a 1:1:1 ratio: * Rapamycin cream, topical (0.6% rapamycin) * Rapamycin cream, topical (1.0% rapamycin) * Placebo The stain will be divided into two parts. One part will be treated only with PDL and the other will be treated with both PDL and the assigned cream. Cream will be applied once daily for 12 weeks. During this phase of the study, four clinical visits will occur, one every 4 weeks for 12 weeks. Assessment of the extent and severity of birthmark size and colour will be performed at randomization, at each clinical visit, and at follow-up using photography and percentage improvement ratings. Safety will be assessed by recording all adverse events experienced and testing blood rapamycin concentration at prior to treatment and at the last clinical visit. Follow-up will be performed 28 days after the last cream application. An extra PDL session will be optionally provided at the follow-up appointment. If PDL treatment occurs at the follow-up visit, a further follow-up phone call will occur 7±2 days after the second PDL session to assess concomitant medications and adverse events.
Interventions
DRUGRapamycin cream
Application of rapamycin cream to port wine birthmark
PROCEDUREPulsed dyed laser
Pulsed dyed laser (PDL) treatment of port wine birthmark
Sponsors
AFT Pharmaceuticals, Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
A Phase II, proof of concept, double-blind, placebo-controlled, randomized, parallel-group, dose-response comparison, with a secondary self-controlled assessment
Eligibility
Sex/Gender
ALL
Age
No minimum to 10 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients aged ≤ 10 years on the day informed consent is obtained 2. Patients presenting either facial, neck, or upper trunk port-wine stains 3. Port wine stain size of at least 5 cm tall x 2.5 cm wide (2x1 inches) 4. Patients (or their legal representatives) capable of understanding the explanation of the clinical trial, and who give written informed consent for participation 5. Patients (or their legal representatives) able to maintain patient diaries following the instructions of the investigator or sub-investigator 6. Patients (or their guardians) are willing and able to follow instructions to only apply cream to part of their port-wine stain 7. Skin type classified as either I, II, III or IV on the Fitzpatrick scale 8. Patients who are indicated for PDL treatment and accept this treatment 9. Patients who respond to PDL with purpura or blanching
Exclusion criteria
1. Skin type classified as either V or VI on the Fitzpatrick scale 2. Patients with PWS in extremities and/or acral areas 3. Patients unwilling or unable to carry out the treatment plan or follow-up assessment 4. Patients with serious skin lesions such as erosions or ulcers 5. Patients with known hypersensitivity to any component of the study product 6. Patients who have received rapamycin/sirolimus, everolimus, or temsirolimus within 3 months of enrolment 7. Patients who have received laser therapy or surgical therapy to treat PWS within 3 months prior to trial enrolment 8. Patients who have received 5 or more PDL treatments previously 9. Patients who participated in any other clinical trial within 3 months prior to the day of enrolment 10. Patients judged unsuitable for this clinical trial by the investigator or sub-investigator 11. Pregnant or lactating females 12. Sexually active females of childbearing potential not using adequate contraception and sexually active males not using adequate contraception\* 13. Patients with immune dysfunction or receiving any form of immunosuppression
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinic Objective improvement rating at week 12 | From before laser treatment to the end of treatment after 12 weeks of cream application | The average percentage improvement (0-100% with higher scores being a better outcome) of port wine stain appearance in the cream treated area from baseline to week 12, or at last visit if early withdrawal/discontinuation occurs, as assessed by the principal investigator during the clinic visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjective improvement rating (all timepoints) | From before laser treatment to the end of treatment after 12 weeks of cream application | Subjective (patient or parent/caregiver) improvement rating (0-100% with higher scores being a better outcome) of port wine stain from baseline after 0, 4, 8 and 12 weeks of treatment. |
| Clinic Objective improvement rating (all timepoints) | From before laser treatment to the end of treatment after 12 weeks of cream application | Clinic Objective (investigator) improvement rating (0-100% with higher scores being a better outcome) in port wine stain from baseline after 0, 4, 8 and 12 weeks of treatment |
| Photographic Objective improvement rating (all timepoints) | From before laser treatment to the end of treatment after 12 weeks of cream application | Photographic Objective improvement rating (0-100% with higher scores being a better outcome), assessed by a committee of three dermatologists, in port wine stain from baseline after 0, 4, 8 and 12 weeks of treatment |
Countries
Spain, United States
Contacts
CONTACTLaura Boddington, PhD
STUDY_DIRECTORIoana Stanescu
AFT Pharmaceuticals
Outcome results
None listed