Sirolimus Gel for Genetic Disorders

(TOIVA Trial)

Recruiting at 9 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

Trial Summary

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.

What data supports the effectiveness of the drug Sirolimus Gel for Genetic Disorders?

Research shows that topical rapamycin (another name for sirolimus) has been effective in treating facial angiofibromas, a skin condition related to tuberous sclerosis complex, with over 90% of patients showing improvement. This suggests that sirolimus gel could be effective for similar skin-related genetic disorders. ^{1 2 3 4 5}

Is topical sirolimus safe for use in humans?

Topical sirolimus (rapamycin) has been used safely in various formulations for treating facial angiofibromas in patients with tuberous sclerosis complex. Studies involving different concentrations and formulations have shown it to be generally safe, with no significant safety concerns reported. ^{1 2 4 6 7}

How is the drug Sirolimus Gel different from other treatments for genetic disorders?

Sirolimus Gel is unique because it is a topical formulation specifically designed to treat skin lesions associated with genetic disorders like tuberous sclerosis, using a higher concentration (3.9%) compared to other formulations that typically use lower concentrations. This gel form allows for direct application to affected areas, potentially reducing systemic side effects and improving patient comfort. ^{1 3 4 8 9}

What is the purpose of this trial?

A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX022 (sirolimus) Topical Gel 3.9% in the Treatment of Cutaneous Venous Malformations

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Formulation and characterization of a 0.1% rapamycin cream for the treatment of Tuberous Sclerosis Complex-related angiofibromas. [2017]

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

Topical sirolimus: Difference between compounded preparations and commercial oral solution. [2021]

3. India pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. 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]

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

A Review of Topical Sirolimus for the Treatment of Facial Angiofibromas in Tuberous Sclerosis Complex. [2023]

7. France 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Long-term stability of 0.1% rapamycin hydrophilic gel in the treatment of facial angiofibromas. [2021]

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

Successful topical rapamycin treatment for facial angiofibromata in two children. [2015]