Rapamycin Gel for Microcystic Lymphatic Malformations

(SELVA Trial)

Recruiting at 16 trial locations

Overseen By Kathy Goin

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Palvella Therapeutics, Inc.

Disqualifiers: Vascular malformations, Severe systemic symptoms, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

SELVA: A Multicenter, Phase 3 Baseline-Controlled Study Evaluating the Safety and Efficacy of QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations The main purpose of this study is to assess the change in microcystic lymphatic malformations IGA after 24 weeks of treatment with QTORIN 3.9% Rapamycin Anhydrous Gel in approximately 40 participants with microcystic lymphatic malformations. Efficacy will be evaluated at 24 weeks and patients have the option of continuing on treatment for \>24 weeks.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How is QTORIN 3.9% Rapamycin Anhydrous Gel different from other drugs for microcystic lymphatic malformations?

QTORIN 3.9% Rapamycin Anhydrous Gel is unique because it is a topical formulation specifically designed for skin application, which may offer better absorption and fewer side effects compared to oral or systemic treatments. This gel uses a higher concentration of rapamycin than other topical formulations, potentially enhancing its effectiveness for treating microcystic lymphatic malformations. ^{1 2 3 4 5}

Research Team

Joyce Teng

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for individuals over the age of 6 with a confirmed diagnosis of superficial or cutaneous microcystic lymphatic malformation. It's not suitable for those with vascular malformations that could affect evaluation, severe systemic symptoms from complicated vascular anomalies, treatment areas within wet mucosa or the orbital rim, or if pregnant.

Inclusion Criteria

I am at least 6 years old.

I have a confirmed superficial skin lymphatic issue.

Exclusion Criteria

My vascular malformations do not affect the assessment of my lymphatic malformation.

I have severe symptoms from vascular anomalies needing treatment.

My treatment area is mainly in wet mucosa or near the eye socket.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive QTORIN 3.9% Rapamycin Anhydrous Gel for 24 weeks to assess changes in microcystic lymphatic malformations

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants have the option of continuing on treatment for more than 24 weeks

Treatment Details

Interventions

• QTORIN 3.9% Rapamycin Anhydrous Gel (mTOR Inhibitor)

Trial Overview The study aims to compare the effectiveness of QTORIN 3.9% Rapamycin Anhydrous Gel versus a placebo in treating microcystic lymphatic malformations. Participants will be randomly assigned to receive either the gel or placebo and monitored over 24 weeks.

Participant Groups

Group I: Active Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Palvella Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

380+

FDA Office of Orphan Products Development

Collaborator

Trials

73

Recruited

6,400+

Findings from Research

Topical rapamycin ointment (1%) has shown promising results in treating microcystic lymphatic malformations (MLM) in two pediatric cases, leading to significant improvement in symptoms and complications after 4 months of treatment.

Both patients experienced marked reductions in discomfort and exudation without major side effects, suggesting that topical rapamycin could be a safe and effective alternative to more aggressive treatments for MLM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microcystic Lymphatic Malformation Successfully Treated With Topical Rapamycin. García-Montero, P., Del Boz, J., Sanchez-Martínez, M., et al.[2017]

A phase 2 trial involving 55 patients is investigating the efficacy and safety of 0.1% topical sirolimus for treating cutaneous microcystic lymphatic malformations (CMLMs) over 12 weeks, with the potential for long-term benefits assessed at 20 weeks and 12 months.

If proven effective, topical sirolimus could become a non-invasive first-line treatment option for CMLMs, significantly improving patient quality of life and management of this rare condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial. Leducq, S., Caille, A., Barbarot, S., et al.[2021]

A comparative study of various rapamycin formulations for treating facial angiofibromas revealed that the type of vehicle significantly affects drug absorption, with hydrogels being the most effective, followed by creams and lipophilic ointments.

The study emphasizes the importance of the soluble state and concentration of rapamycin in formulations to maximize its therapeutic effectiveness, providing valuable insights for optimizing topical treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed. Le Guyader, G., Do, B., Vieillard, V., et al.[2020]

Topical rapamycin delivered through mixed polymeric micelles, particularly those made with TPGS and poloxamer, shows improved stability and skin bioavailability for treating facial angiofibromas in tuberous sclerosis complex.

The optimized formulation of mixed-micelle hydrogels containing 0.1% rapamycin remains stable for up to 3 months and provides better distribution on human skin compared to traditional hydroalcoholic gel formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mixed Polymeric Micelles for Rapamycin Skin Delivery. Le Guyader, G., Do, B., Rietveld, IB., et al.[2022]

Topical rapamycin has been shown to be an effective and safe treatment for facial angiofibromas in patients with tuberous sclerosis complex (TSC), with over 90% of patients experiencing improvement, especially when treatment begins at early stages.

Among various formulations tested, ointment and gel are preferred, with a 0.1% concentration suggested as the first choice, although further studies are needed to determine the optimal formulation and concentration for the best outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex-An update. Balestri, R., Rizzoli, L., Pedrolli, A., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Microcystic Lymphatic Malformation Successfully Treated With Topical Rapamycin. [2017]

2. England pubmed.ncbi.nlm.nih.gov

Topical sirolimus 0.1% for treating cutaneous microcystic lymphatic malformations in children and adults (TOPICAL): protocol for a multicenter phase 2, within-person, randomized, double-blind, vehicle-controlled clinical trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Comparison of the In Vitro and Ex Vivo Permeation of Existing Topical Formulations Used in the Treatment of Facial Angiofibroma and Characterization of the Variations Observed. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Mixed Polymeric Micelles for Rapamycin Skin Delivery. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Analysis of current data on the use of topical mTOR inhibitors in the treatment of facial angiofibromas in tuberous sclerosis complex-An update. [2023]