Sirolimus Gel for Genetic Disorders

(TOIVA Trial)

Recruiting at 10 trial locations

Overseen By Emily Cook

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Palvella Therapeutics, Inc.

Disqualifiers: Mucosa, Bone, Tissue, others

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

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a topical gel called PTX-022 (Sirolimus) to determine its safety and effectiveness in treating skin venous malformations (cVM), which are clusters of abnormal veins on the skin. The goal is to assess whether this gel can improve the appearance and symptoms of these skin issues. Eligible participants have visible venous malformations on their skin, not primarily in wet areas like the mouth or eyes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to developing a potentially effective treatment.

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

The trial information does not specify whether you need to stop taking your current medications. Please consult with the trial coordinators for more details.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Studies have shown that PTX-022, a 3.9% sirolimus gel, is generally safe for humans. Research indicates that people tolerate this gel well, and earlier studies have reported no major safety issues.

In previous trials, this sirolimus gel was tested for similar conditions, and the results showed it to be safe. Participants did not experience serious side effects, suggesting that the gel has a low risk of causing severe problems.

It's important to remember that this gel is still under study. However, the findings so far support its safety for treating skin-related health issues. Always consider discussing any concerns with a healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for genetic disorders, which often involves systemic treatments or oral medications, PTX-022 is a topical gel containing Sirolimus. This gel is unique because it allows for targeted application directly to the skin, minimizing systemic exposure and potentially reducing side effects. Researchers are excited about PTX-022 because Sirolimus, an mTOR inhibitor, works by targeting the cellular pathways involved in these disorders, offering a novel approach that could lead to more effective management of symptoms with fewer risks than current treatments.

What evidence suggests that this treatment might be an effective treatment for cutaneous venous malformations?

Research has shown that PTX-022, a gel containing 3.9% sirolimus, may help treat skin issues such as cutaneous venous malformations. Studies have found that this gel effectively reduces the size and symptoms of these skin problems. Users of this gel have experienced significant improvements in their condition. The gel targets abnormal blood vessels, helping to normalize them and reduce visible skin changes. This evidence suggests that the sirolimus gel could be a helpful treatment for these types of skin conditions. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with visible varicose veins, specifically cutaneous venous malformations (cVM), which may include a small part (<30%) of lymphatic malformation. It's not suitable for those who don't meet the specific criteria of having cVM.

Inclusion Criteria

-

I have a visible vein malformation on my skin with less than 30% lymphatic involvement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PTX-022 (Sirolimus) Topical Gel 3.9% for the treatment of cutaneous venous malformations

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PTX-022 (Sirolimus) Topical Gel 3.9%

Trial Overview The study tests PTX-022 (Sirolimus) Topical Gel at 3.9% concentration to see if it's safe and effective in treating skin-visible varicose veins. This Phase 2 trial compares patients' conditions before and after treatment.

How Is the Trial Designed?

Group I: Single-arm, open-label Experimental Treatment 1 Intervention

PTX-022 (Sirolimus) Topical Gel 3.9% is already approved in United States for the following indications:

Approved in United States as Hyftor for:

• Tuberous Sclerosis Complex
• Angiofibroma

Who Is Running the Clinical Trial?

Palvella Therapeutics, Inc.

Lead Sponsor

Trials

8

Recruited

380+

Published Research Related to This Trial

A 17-year-old girl with tuberous sclerosis showed significant improvement in facial angiofibromas after using a compounded 0.1% sirolimus ointment for 3 months, with further enhancement observed after increasing the concentration to 1% for an additional month.

The treatment was well-tolerated with no reported side effects, suggesting that topical sirolimus could be a safe and effective option for managing angiofibromas in young patients, although further randomized controlled trials are needed to confirm its long-term efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Facial angiofibromas of tuberous sclerosis treated with topical sirolimus in an Indian patient. Vasani, RJ.[2018]

A new hydro-alcoholic gel formulation containing solubilised rapamycin was developed, showing improved skin penetration and stability over one year at 4°C, which is crucial for treating facial angiofibromas in tuberous sclerosis.

The gel maintained its physical and microbiological stability without significant changes in pH or rapamycin concentration, suggesting it could be a more tolerable and effective alternative to existing petrolatum-based formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas. Le Guyader, G., Vieillard, V., Andrieux, K., et al.[2021]

Topical sirolimus (rapamycin) has been successfully used to treat facial angiofibromata in two children, demonstrating its potential as an effective therapy for this condition.

The report highlights existing literature that supports the effectiveness of topical sirolimus in inhibiting tumor growth associated with tuberous sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful topical rapamycin treatment for facial angiofibromata in two children. Pynn, EV., Collins, J., Hunasehally, PR., et al.[2015]

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 cream, used to treat facial angiofibromas in patients with tuberous sclerosis, was well tolerated and showed sustained efficacy over a mean treatment duration of 33 months, with 67.1% of patients rating its effectiveness at 8/10 or higher.

The safety of the topical rapamycin formulation was also highly rated, with 84.8% of patients giving it a score of 8/10 or higher, indicating it is a safe option for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A survey of patients with facial angiofibromas associated with tuberous sclerosis complex: Short-, medium- and long-term efficacy and safety of topical rapamycin. Sigg, N., Fouquet, J., Morin, D., et al.[2023]

A new 0.1% rapamycin cream formulation has been successfully developed for treating facial angiofibromas associated with Tuberous Sclerosis Complex, showing good solubilization and stability over 85 days.

The cream maintained its quality, including microbial safety and physical properties, throughout storage, and is currently being used by patients, with efficacy and tolerance data expected in future reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas. Bouguéon, G., Lagarce, F., Martin, L., et al.[2017]

Topical sirolimus is an important treatment for various skin disorders, but there is currently no FDA-approved topical formulation available, leading to the use of compounded preparations.

This article emphasizes the significant differences between commercially available oral sirolimus solutions and compounded topical formulations, which is crucial for healthcare providers when considering treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Topical sirolimus: Difference between compounded preparations and commercial oral solution. Brichta, L., Carver, JG., Carver DeKlotz, CM.[2021]

Topical sirolimus 0.2% gel has been shown to significantly improve the size and redness of facial angiofibromas in patients with tuberous sclerosis complex, with a response rate of 60% compared to 0% in the placebo group after 12 weeks of treatment.

The treatment has a favorable safety profile, with no serious adverse events reported and only mild reactions like dry skin, making it a promising noninvasive alternative to surgery for managing these skin lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex. Dao, DD., Pixley, JN., Akkurt, ZM., et al.[2023]

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/NCT05050149

Study Evaluating the Safety and Efficacy of PTX-022 ... This study evaluates the safety and efficacy of PTX-022 (sirolimus) Topical Gel 3.9% w/w in the treatment of Microcystic Lymphatic Malformations.

3. ovid.com ovid.com/jnls/jova/pdf/10.1097/jova.0000000000000101~phase-2-study-of-the-safety-and-efficacy-of-qtorin-rapamycin

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

4. ir.palvellatx.com ir.palvellatx.com/news-releases/news-release-details/palvella-therapeutics-announces-scientific-publication-lymphatic

Release Details The manuscript supports the scientific rationale and clinical potential of Palvella's QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin) ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/sirolimus-topical-gel-ptx-022?pn=1

Clinical Trials Using Sirolimus Topical Gel PTX-022 - NCI Review the clinical trials studying sirolimus topical gel ptx-022 on this list and use the filters to refine the results by age and location.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05643872

NCT05643872 | A Study Evaluating the Safety and ... The purpose of this OLT study is to investigate the safety of long term exposure and pharmacokinetics (PK) of QTORIN rapamycin 3.9% anhydrous gel or "PTX-022".