Rapamycin Dose-Ranging Efficacy Study in Port Wine Stains

Rapamycin Dose-Ranging Efficacy Study: A Phase II, Proof of Concept, Double-blind, Placebo-controlled, Randomized, Parallel-group, Dose-response Comparison of the Effects of Different Strengths of Rapamycin Cream Applied Topically in Subjects Diagnosed With Port Wine Stains

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Port Wine Stains
• Intervention / Treatment: Drug: Rapamycin cream; Procedure: Pulsed dyed laser

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Laura Boddington, PhD; Phone Number: 735 +6494880232; Email: laura.boddington@aftpharm.com

Study Locations

• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08950
      • Sant Joan de Déu University Hospital
      • Contact: Study Coordinator - Unitat d'Investigacio Clinica; Phone Number: +34 670989833; Email: mateu.torres@sjd.es
      • Principal Investigator: Marta Ivars, MD
• United States
  • Texas
    • Corpus Christi, Texas, United States, 78411
      • Driscoll Children's Hospital
      • Contact: Erin Richmond, MS, RN, CCRP; Phone Number: 361-694-5978; Email: erin.richmond@dchstx.org
      • Principal Investigator: Denise Metry, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.6% rapamycin; 0.6% rapamycin cream applied daily	Drug: Rapamycin cream; Application of rapamycin cream to port wine birthmark; Procedure: Pulsed dyed laser; Pulsed dyed laser (PDL) treatment of port wine birthmark
Experimental: 1.0% rapamycin cream; 1.0% rapamycin cream applied daily	Drug: Rapamycin cream; Application of rapamycin cream to port wine birthmark; Procedure: Pulsed dyed laser; Pulsed dyed laser (PDL) treatment of port wine birthmark
Placebo Comparator: Placebo cream; Placebo cream applied daily	Procedure: Pulsed dyed laser; Pulsed dyed laser (PDL) treatment of port wine birthmark

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinic Objective improvement rating at week 12	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.	From before laser treatment to the end of treatment after 12 weeks of cream application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective improvement rating (all timepoints)	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.	From before laser treatment to the end of treatment after 12 weeks of cream application
Clinic Objective improvement rating (all timepoints)	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	From before laser treatment to the end of treatment after 12 weeks of cream application
Photographic Objective improvement rating (all timepoints)	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	From before laser treatment to the end of treatment after 12 weeks of cream application

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective improvement rating change at follow-up	Subjective (patient or parent/caregiver) improvement rating (0-100% with higher scores being a better outcome) change of cream treated area from baseline at follow-up visit	From before laser treatment to follow-up visit (16 weeks)
Subjective improvement rating (post-treatment)	Subjective (patient or parent/caregiver) improvement rating (0-100% with higher scores being a better outcome) change of cream treated area between week 12 and follow-up	4 weeks between end of treatment and follow-up visit
Clinic Objective improvement rating change at follow-up	Clinic Objective (investigator) improvement rating (0-100% with higher scores being a better outcome) change of cream treated area from baseline at follow-up visit	From before laser treatment to follow-up visit (16 weeks)
Clinic Objective improvement rating (post-treatment)	Clinic Objective (investigator) improvement rating (0-100% with higher scores being a better outcome) change of cream treated area between week 12 and follow-up	4 weeks between end of treatment and follow-up visit
Photographic Objective improvement rating change at follow-up	Photographic Objective improvement rating (0-100% with higher scores being a better outcome), assessed by a committee of three dermatologists, change of cream treated area from baseline at follow-up visit	From before laser treatment to follow-up visit (16 weeks)
Photographic Objective improvement rating (post-treatment)	Photographic Objective improvement rating (0-100% with higher scores being a better outcome), assessed by a committee of three dermatologists, change of cream treated area between week 12 and follow-up	4 weeks between end of treatment and follow-up visit
Categorical Improvement of port wine stain	Categorical Improvement (5-point scale with higher scores being a better outcome) of port wine stain in cream treated area from baseline after 12 weeks of treatment.	From before laser treatment to the end of treatment after 12 weeks of cream application
Colorimetry rating (all timepoints)	Change in extent and intensity of port wine stain colour of the cream treated area from baseline at weeks 0, 4, 8, 12 and follow-up/last assessment, measured using a colorimetry system through standardized clinical photographs	From before laser treatment to the follow-up visit (16 weeks)
Colorimetry intra-patient rating	Difference in extent and intensity of port wine stain colour between the two treatment areas (laser+cream or laser only) of each individual at each assessment (pre-laser baseline, weeks 0, 4, 8, 12 and follow-up/last assessment) using the colorimetry system	From before laser treatment to the follow-up visit (16 weeks)
Subjective intra-patient rating	Difference in subjective (patient or parent/caregiver) improvement rating (0-100% with higher scores being a better outcome) of port wine stain between the treatment areas (laser+cream or laser only) of each individual at each assessment (week 0, 4, 8, 12 and follow-up/last assessment)	From start of cream treatment to the follow-up visit (16 weeks)
Clinic Objective intra-patient rating	Difference in clinic objective (investigator) improvement rating (0-100% with higher scores being a better outcome) of port wine stain between the treatment areas (laser+cream or laser only) of each individual at each assessment (week 0, 4, 8, 12 and follow-up/last assessment)	From start of cream treatment to the follow-up visit (16 weeks)
Photographic Objective intra-patient rating	Difference in photographic objective (committee) improvement rating (0-100% with higher scores being a better outcome) of port wine stain between the treatment areas (laser+cream or laser only) of each individual at each assessment (week 0, 4, 8, 12 and follow-up/last assessment)	From start of cream treatment to the follow-up visit (16 weeks)

Collaborators and Investigators

• Sponsor: AFT Pharmaceuticals, Ltd.
• Investigators: Study Director: Ioana Stanescu, AFT Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: February 22, 2026
• First Submitted That Met QC Criteria: February 22, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 26, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: dose ranging; phase 2; sirolimus; rapamycin; proof of concept; adjunct therapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Vascular Tissue; Hemangioma; Hemangioma, Capillary
• Other Study ID Numbers: AFT-RAP-01; 2025-520821-19-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No