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

20 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug rapamycin for treating vitiligo?

Research shows that rapamycin, also known as sirolimus, has been effective in treating various skin conditions like angiofibromas and acanthosis nigricans by reducing inflammation and abnormal cell growth. This suggests it might also help with vitiligo, a condition where skin loses its pigment. ^{1 2 3 4 5}

Is topical rapamycin safe for use in humans?

Topical rapamycin, also known as sirolimus, has been used safely in humans for various skin conditions, with a lower risk of kidney, nerve, and certain immune system complications compared to other similar drugs. However, it can cause skin and mouth problems, which can range from mild to severe. ^{1 2 4 6 7}

How is the drug rapamycin unique for treating vitiligo?

Rapamycin is unique for treating vitiligo because it is applied topically and works by inhibiting mTOR, a protein that affects cell growth and immune response, which may help in reducing skin inflammation and promoting repigmentation. Unlike other treatments, rapamycin has a lower risk of causing kidney or nerve problems and is being explored for its potential in treating various skin conditions. ^{1 2 3 8 9}

What is the purpose of this trial?

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 of their body and a different cream on the other for several months. The study will also check patient satisfaction and any side effects. Rapamycin has been studied for its potential to stabilize cyst growth in ADPKD, but larger trials showed no benefit on kidney function.

Research Team

Ahmad Aleisa, MD

Principal Investigator

Medical University of South Carolina

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

References

1. Canada pubmed.ncbi.nlm.nih.gov

Sirolimus: a therapeutic advance for dermatologic disease. [2014]

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

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

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

Why Is Rapamycin Not a Rapalog? [2023]

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

Topical rapamycin for acanthosis nigricans in the Fitzpatrick IV/V adolescent population. [2021]

5. United States 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. [2014]

6. France pubmed.ncbi.nlm.nih.gov

Use of mTOR inhibitors (rapalogs) for the treatment of skin changes in tuberous sclerosis complex. [2023]

7. Denmark pubmed.ncbi.nlm.nih.gov

mTOR inhibitor-associated dermatologic and mucosal problems. [2021]

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

Topical rapamycin (sirolimus) for the treatment of uncomplicated tufted angiomas in two children and review of the literature. [2018]

9. 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]