Topical Rapamycin for Vitiligo

Overseen By Courtney Linkous, BS

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Segmental vitiligo, Transplant history, Immunodeficiency, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a cream containing rapamycin, used once daily, can treat vitiligo, a condition causing loss of skin color in patches. The trial will compare two versions of the cream—one with a higher dose and one with a lower dose—to a placebo (a cream with no active ingredients) applied to patches on the opposite side of the body. The goal is to assess which is more effective and whether participants are satisfied with the results. Individuals with nonsegmental vitiligo who are not currently receiving treatment for the condition might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop any current treatment for vitiligo and avoid taking medications that inhibit or strongly induce CYP3A4, an enzyme that affects drug metabolism.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that topical rapamycin, also known as sirolimus, is generally safe for treating skin conditions. In past studies, most side effects were mild, with participants mainly experiencing skin irritation and itching. Importantly, no moderate or severe side effects related to the drug were found.

Rapamycin is applied as a cream once a day on the skin. It has a lower risk of causing kidney, nerve, or certain immune system problems compared to other treatments. This suggests it is quite safe for individuals using it for conditions like vitiligo. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for vitiligo?

Unlike the standard treatments for vitiligo, which often include corticosteroids and light therapy, topical rapamycin offers a unique approach. Rapamycin is an mTOR inhibitor, which means it works by targeting the pathways involved in cell growth and pigmentation, potentially addressing the underlying mechanisms of vitiligo. This trial explores two concentrations: 0.001% and 0.1%, providing a nuanced look at its effectiveness compared to traditional methods. Researchers are excited about rapamycin because it could offer a more targeted therapy with fewer systemic side effects, and the topical application makes it easy to use.

What evidence suggests that topical rapamycin might be an effective treatment for vitiligo?

This trial will compare different concentrations of topical rapamycin for treating vitiligo. Research suggests that a cream with a small amount of rapamycin might help treat this condition. In a recent study, participants who applied a 0.001% rapamycin cream daily showed improvements in skin color in affected areas. Rapamycin adjusts certain cell activities, potentially addressing some underlying issues causing vitiligo. Although more human studies are necessary, these early results offer promise for those with this skin condition. ^{1 2 5 6 7}

Who Is on the Research Team?

Ahmad Aleisa, MD

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

This trial is for people aged 13 and older with nonsegmental vitiligo, which causes loss of skin color in blotches. It's not for those on certain medications affecting the immune system, have had transplants, serious infections, are pregnant or currently treating vitiligo.

Inclusion Criteria

I am 13 years old or older.

You have nonsegmental vitiligo.

Exclusion Criteria

You have a history of weak immune system from birth.

I have had a serious or life-threatening infection in the past.

You have vitiligo on specific areas of your skin or on your mucous membranes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants apply either 0.1% or 0.001% topical rapamycin daily for 6 months to a lesion on one side of the body, and a placebo to the opposite side

6 months

Follow-up visits at 2, 4, and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Rapamycin

Trial Overview The study tests if daily use of a cream called rapamycin can help with vitiligo. Participants will apply two strengths of rapamycin to different body lesions and a placebo to another lesion for six months to compare effectiveness and satisfaction.

How Is the Trial Designed?

Group I: Topical rapamycin 0.001% Experimental Treatment 1 Intervention

Patients randomized to this arm of the study will apply 2 finger tip units (FTU) or 0.5 cc topical rapamycin 0.001% cream daily for 6 months

Group II: Topical rapamycin 0.1% Active Control 1 Intervention

Patients randomized to this arm of the study will apply 2 FTU (0.5 cc) topical rapamycin 0.1% cream daily for 6 months

Group III: Placebo Placebo Group 1 Intervention

All patients will apply 2 FTU (0.5 cc) topical placebo cream daily for 6 months to the corresponding anatomic location on the opposite side of the body where the experimental drug is not being applied

Rapamycin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis
• Perivascular epithelioid cell tumors

Approved in United States as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis
• Perivascular epithelioid cell tumors

Approved in Canada as Rapamune for:

• Prevention of organ transplant rejection
• Lymphangioleiomyomatosis

Approved in Japan as Rapamune for:

• Prevention of organ transplant rejection

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

American Skin Association

Collaborator

Trials

3

Recruited

60+

Published Research Related to This Trial

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]

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]

Sirolimus has become a foundational therapy for immunosuppression in transplant patients, significantly reducing the risk of acute allograft rejection by allowing over 80% reduction in calcineurin inhibitor exposure, which leads to better long-term renal function despite some increased risks of lymphoceles and impaired wound healing.

The drug also has anti-cancer properties by inhibiting mTOR, reducing tumor incidence in patients, and is relatively non-nephrotoxic, allowing for the withdrawal of steroid therapy and lower rates of viral infections, making it a promising option in immunosuppressive regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fifteen years of clinical studies and clinical practice in renal transplantation: reviewing outcomes with de novo use of sirolimus in combination with cyclosporine. Kahan, BD.[2014]

Sirolimus (rapamycin) is an effective immunosuppressant approved for preventing graft rejection in kidney transplants, with a lower risk of complications compared to other immunosuppressants.

Recent findings suggest that sirolimus may also have potential in treating skin disorders and extending lifespan, making it a promising candidate for addressing age-related diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. Peters, T., Traboulsi, D., Tibbles, LA., et al.[2014]

Topical rapamycin (sirolimus) has shown significant and temporary efficacy in reducing the size and visibility of facial angiofibromas in patients with Tuberous Sclerosis Complex (TSC), with about 80% of patients in a study at Angers University Hospital experiencing impressive and sustained responses.

Long-term use of topical rapamycin is necessary to maintain skin improvements, and while the treatment is generally well-tolerated, there are ongoing concerns about the cost and accessibility of effective formulations for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of mTOR inhibitors (rapalogs) for the treatment of skin changes in tuberous sclerosis complex. Farges, D., Sigg, N., Ville, D., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05342519?term=Rapamycin&viewType=Table&rank=5

NCT05342519 | Daily Topical Rapamycin for Vitiligo The purpose of this study is to determine if once daily dosed topical rapamycin is effective for the treatment of patients with vitiligo. Participants will ...

2. clinicaltrial.be clinicaltrial.be/en/details/29223?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Daily Topical Rapamycin for Vitiligo Another recent study in humans showed that doses of 0.5cc daily of 0.001% of the topical formulation are able to achieve improvement in ...

3. vrfoundation.org vrfoundation.org/news_items/topical-rapamycin-could-this-be-vitiligos-next-big-breakthrough

Topical Rapamycin: Could This Be Vitiligo's Next Big ... If topical rapamycin helps modulate mTOR activity in the skin, it could reset some of the cellular dysfunctions at the heart of vitiligo in ways that current ...

4. withpower.com withpower.com/trial/phase-2-vitiligo-5-2022-392a4

Topical Rapamycin for Vitiligo · Info for Participants This trial tests if a daily cream with rapamycin can help treat vitiligo, a skin condition causing color loss. Participants will use the cream on one side ...

5. jamanetwork.com jamanetwork.com/data/journals/derm/937360/doi180010supp1_prod.pdf

Efficacy and Safety of Topical Rapamycin in Patients With ... 3,8 Trials of orally in- gested mTOR inhibitors, including rapamycin and its deriva- tives, have demonstrated positive results for TSC-related ...

6. academic.oup.com academic.oup.com/ced/advance-article-abstract/doi/10.1093/ced/llae275/7715941

Topical sirolimus in dermatology: a systematic review Topical sirolimus was generally well tolerated; most reported adverse effects were localized irritation and pruritus. Ointment-based preparations and once-daily ...

7. ctv.veeva.com ctv.veeva.com/study/daily-topical-rapamycin-for-vitiligo

Daily Topical Rapamycin for Vitiligo - ClinicalTrials.Veeva The purpose of this study is to determine if once daily dosed topical rapamycin is effective for the treatment of patients with vitiligo.