Rapamycin Gel for Microcystic Lymphatic Malformations

(SELVA Trial)

Recruiting at 16 trial locations

Overseen By Emily Cook

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Palvella Therapeutics, Inc.

Disqualifiers: Vascular malformations, Severe systemic symptoms, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a gel called QTORIN 3.9% Rapamycin Anhydrous Gel to determine its effectiveness for individuals with microcystic lymphatic malformations, which are small, fluid-filled skin growths. The study evaluates the gel's efficacy after 24 weeks of use. It seeks participants with visible growths on the skin who do not have other vascular malformations that could affect the results. Participants may continue using the gel beyond 24 weeks if desired. This study is crucial for discovering new treatments for these skin conditions. As a Phase 3 trial, this treatment represents the final step before FDA approval, allowing participants to contribute to a potentially groundbreaking therapy.

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.

Is there any evidence suggesting that QTORIN 3.9% Rapamycin Anhydrous Gel is likely to be safe for humans?

Research has shown that QTORIN 3.9% Rapamycin Anhydrous Gel is generally safe. In a previous study, participants using this gel reported good safety outcomes, with no major concerns. Some users might experience mild skin irritation, a common and usually non-serious side effect of skin treatments.

The gel contains rapamycin, a drug often used to prevent organ rejection, but in this form, it is applied to the skin. This application helps avoid some side effects associated with oral intake, such as immune system issues, making it less likely to cause systemic problems. Overall, evidence from past studies suggests the gel is safe for individuals with microcystic lymphatic malformations. ^{1 2 3 4 5}

Why are researchers excited about this possible treatment for microcystic lymphatic malformations?

Unlike the standard treatments for microcystic lymphatic malformations, which often involve sclerotherapy or surgery, QTORIN 3.9% Rapamycin Anhydrous Gel offers a novel approach by using a topical gel formulation. This gel leverages rapamycin, a compound known for its ability to inhibit a specific protein pathway involved in abnormal cell growth. Researchers are excited about this treatment because it provides a non-invasive option that directly targets the malformations, potentially reducing size and symptoms with fewer side effects than systemic treatments.

What evidence suggests that QTORIN 3.9% Rapamycin Anhydrous Gel might be an effective treatment for microcystic lymphatic malformations?

Research has shown that QTORIN 3.9% Rapamycin Anhydrous Gel, which participants in this trial will receive, may help treat microcystic lymphatic malformations. Patients in previous studies experienced significant improvements in their condition. These studies found that the gel can reduce the size and severity of these malformations. Both patients and doctors observed meaningful changes, indicating its potential effectiveness. The gel delivers rapamycin, a substance that slows the growth of abnormal blood vessels, directly to the affected area. These findings suggest that the gel could be a valuable option for people with this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Joyce Teng

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• QTORIN 3.9% Rapamycin Anhydrous Gel

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. journals.lww.com journals.lww.com/jova/fulltext/2024/12000/phase_2_study_of_the_safety_and_efficacy_of_qtorin.8.aspx

Phase 2 study of the safety and efficacy of QTORIN... This Phase 2 study provides compelling evidence of the safety and efficacy of QTORIN rapamycin, a novel 3.9% topical sirolimus formulation, for the treatment ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06239480

SELVA: A Phase 3 Study Evaluating QTORIN 3.9% ... 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 ...

3. ir.palvellatx.com ir.palvellatx.com/news-releases/news-release-details/palvella-therapeutics-announces-qtorintm-rapamycin-39-anhydrous

Palvella Therapeutics Announces QTORIN™ Rapamycin ... Based on data from Phase 2 and clinician interviews, the primary endpoint is the fit-for-purpose Microcystic Lymphatic Malformations ...

4. texaschildrens.org texaschildrens.org/departments/cancer-and-hematology-center/clinical-trials-and-novel-therapies/phase-3-study

Vascular Anomalies Center A Phase 3 Study Evaluating ... This Phase 3 study evaluates the QTORIN 3.9% rapamycin gel topical treatment in individuals aged 3 years and older with microcystic lymphatic malformations.

5. jidonline.org jidonline.org/article/S0022-202X(25)00282-9/abstract

QTORIN rapamycin 3.9% anhydrous gel: A Novel, Dermal ... In a baseline-controlled Phase 2 study for mLM, QTORIN rapamycin demonstrated statistically and clinically significant improvements according to patient and ...

6. thedermdigest.com thedermdigest.com/palvella-therapeutics-qtorin-rapamycin-3-9-anhydrous-gel-shows-promise-for-microcystic-lms/

Palvella Therapeutics' QTORIN Rapamycin 3.9% ... QTORIN rapamycin 3.9% anhydrous gel is showing promise in the treatment of microcystic lymphatic malformations, according to a presentation.