Hemangioma Skin
Conditions
Brief summary
This is a 48-week, open-label pilot study to evaluate the safety, including systemic exposure and skin tolerability, and preliminary efficacy of 5% simvastatin ointment in the treatment of 15 children with newly diagnosed superficial proliferating IH. The primary objective: To evaluate the safety, including systemic exposure and skin tolerability of topical treatment with 5% simvastatin ointment for superficial proliferating IH over 48 weeks. The secondary objective: 1.1 To evaluate the efficacy and durability of 5% simvastatin ointment when topical treatment is administered twice daily for 24 weeks, followed by a 24-week post-treatment follow-up period. Evaluation is performed at each clinic visit via investigator global assessment (IGA) based on standardized 3D digital photography and hemangioma activity score (HAS). 1.2 To evaluate the impact of 5% simvastatin ointment on quality of life using the IH-QoL questionnaire. The exploratory objective: To explore whether clinical response and regrowth following topical 5% simvastatin treatment are associated with SOX18-mevalonate pathway-axis activation in infantile hemangioma tissue.
Interventions
DRUG5% simvastatin ointment
5% simvastatin ointment will be applied directly on IH lesion twice per day for 24 weeks
Sponsors
Joyce Teng
Stanford University
National Institutes of Health (NIH)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Months to 6 Months
Healthy volunteers
No
Inclusion criteria
Participants may be included in the study only if they meet all of the following criteria: 1. Healthy children aged between 3-6 months without medical disorders that contradict topical statin treatment. 2. Infants with newly diagnosed superficial IH. \[3\] Participants must possess at least one IH lesion with the longest diameter equal to or greater than 1 cm but less than 1% BSA, located on any part of the body except the lips. \[4\] Written informed consent from the parent(s)/guardian(s) must be obtained before any study procedure is performed. \[5\] Parent(s)/guardian(s) are willing to comply with the study protocol
Exclusion criteria
Participants meeting any of the following criteria will not be eligible to participate in the study: 1. IH is primarily characterized as subcutaneous, and deep, with minimal cutaneous involvement for evaluation. 2. IH with active ulceration at screening visit. 3. IH to be treated involving the lips mainly. 4. IH with high-risk criteria that need systemic propranolol treatment to avoid the delay with standard treatment 5. Participants with concurrent skin conditions that may impede accurate clinical assessment of the IH. 6. Participants with hereditary or metabolic disorders requiring systemic statin therapy. 7. Participants who are allergic to statins, or other ingredients present in the topical medication. 8. Participants who have received any of the following treatments for their IH: i) Topical medical therapy, i.e. imiquimod, sirolimus, timolol, intermediate or high strength steroids, etc. within the past 4 weeks ii) Systemic medical therapy, i.e. beta blockers, steroids, sirolimus for IH within the past 3 months iii) Surgical intervention including laser treatment within the past 6 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the safety and tolerability of the 5% simvastatin ointment over 48 weeks | Baseline through week 48 | The primary endpoint is the evaluation of the safety and tolerability of the 5% simvastatin ointment over 48 weeks, defined by the following three combined components: * Adverse Events: The incidence, severity, and proportion of participants experiencing adverse events (AEs) from Week 0 through Week 48. * Systemic Exposure: The proportion of participants with detectable serum simvastatin levels, alongside descriptive statistics of measured concentrations, at Week 24 (End of Treatment). * Skin Tolerability: The incidence and maximum severity score of local skin reactions at the treatment site at Week 24 (End of Treatment). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks: Key Efficacy Endpoints (Week 24) | Baseline through week 24 | The secondary endpoint is the evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks, defined by the following three combined components: 1\. Key Efficacy Endpoints (Week 24) * Percentage of participants achieving 50% HAS reduction from baseline at week 24 Percentage of participants achieving a 75% HAS reduction from baseline at week 24. * Percentage of participants achieving complete or nearly complete resolution of the targeted IH (IGA 0 or 1), defined as a minimal degree of telangiectasia, skin thickening, and no definitive palpable cutaneous texture changes, at week 24. * Percentage of participants achieving targeted IH stabilization - (no noticeable change to baseline) at week 24. * Percentage of patients whose have 50% improvement captured by 3D photographs and agreed by blinded assessor at week 24 * Percentage of participants with a significant improvement in quality-of-life, defined as \> 50% reduction in the IH-QoL questionnaire score from base |
| To evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks: Treatment Failure and Durability Endpoints | Baseline through week 48 | The secondary endpoint is the evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks, defined by the following three combined components: 2\. Treatment Failure and Durability Endpoints * Disease Progression: Percentage of participants whose targeted IH progresses to the point of requiring systemic therapy, laser, or surgical interventions (resulting in Early Termination). * Treatment Rebound (Durability): Percentage of participants experiencing targeted IH regrowth during the 24-week follow-up period (Weeks 24 to 48), alongside the median and range of time (in weeks) from Week 24 to the first notable rebound |
| To evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks: Time-to-Event Assessments | Baseline through week 48 | The secondary endpoint is the evaluation of the efficacy and durability of the 5% simvastatin ointment over 48 weeks, defined by the following three combined components: 3\. Time-to-Event Assessments * Time to Notable Response: The median and range of time (in weeks) from baseline to the first documented 25% reduction in HAS. * Time to Progression: The median time to progression requiring rescue therapy (systemic, laser, or surgery), estimated using the Kaplan-Meier method. Participants without disease progression will be censored at Week 24 (or at their date of early discontinuation). |
Countries
United States
Contacts
CONTACTJoyce Teng, MD, PhD
CONTACTRamrada Lekwuttikarn, MD
PRINCIPAL_INVESTIGATORJoyce Teng, MD, PhD
Stanford University
Outcome results
None listed