Tapinarof for Palmoplantar Keratoderma

Overseen By Flossy Lincoln

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Indiana University

Must not be taking: Corticosteroids, Retinoids, Vitamin D, others

Disqualifiers: Pregnancy, Hypersensitivity, Other study, 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

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

Compensation: Varies

Number of Visits: 4

Duration: 16 weeks

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a cream called tapinarof to determine its effectiveness for palmoplantar keratoderma, a condition causing thick skin on the palms and soles. The goal is to assess the treatment's efficacy and safety over time. Participants will apply the cream daily to evaluate improvements and the duration of benefits. This trial suits adults diagnosed with palmoplantar keratoderma. 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?

If you are using topical corticosteroids, keratolytic agents, topical retinoids, topical vitamin D ointment, or oral retinoids, you will need to stop taking them and have a 2-week period without these medications before starting the study.

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

Research has shown that tapinarof cream has been tested in clinical trials for conditions like plaque psoriasis and has a good safety record. The most common side effects included small bumps around hair follicles and skin irritation, which are usually mild and easily managed.

Tapinarof is already used for other skin conditions, suggesting it is generally well-tolerated. Although the current study is still investigating its safety for palmoplantar keratoderma, existing data from other uses is reassuring. ^{1 2 3 4 5}

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

Unlike the standard treatments for palmoplantar keratoderma, which often involve topical keratolytics and systemic retinoids, Tapinarof is a topical cream that targets the underlying inflammation. Researchers are excited about Tapinarof because it acts as an aryl hydrocarbon receptor modulator, which can help reduce skin thickening and inflammation without the side effects commonly associated with systemic treatments. Additionally, Tapinarof's once-daily application offers a convenient and potentially more tolerable approach for managing this condition.

What evidence suggests that tapinarof might be an effective treatment for keratoderma?

Research has shown that tapinarof effectively treats skin conditions like psoriasis. In studies, 35.4% to 40.2% of people with psoriasis experienced significant improvement using tapinarof 1% cream. This cream targets specific processes in the skin to reduce inflammation. In this trial, participants will apply tapinarof 1% cream to treat palmoplantar keratoderma. A case study showed improvement in thick skin on the palms and soles, known as palmoplantar keratoderma, when using tapinarof. These findings suggest that tapinarof might help improve this condition by stopping its progression and enhancing skin health. ^{1 2 3 6 7}

Who Is on the Research Team?

David Rosmarin, MD

Principal Investigator

Dermatology

Are You a Good Fit for This Trial?

This trial is for adults with palmoplantar keratoderma, a condition where the skin on palms and soles thickens. Participants should be diagnosed with this condition to qualify. The study will exclude certain individuals based on criteria not specified here.

Inclusion Criteria

Ability to discern and provide written informed consent and voluntarily adhere to all of the protocol requirements

I have been diagnosed with palmoplantar keratoderma.

Exclusion Criteria

Currently participating in another clinical study for the same purpose

Potential or confirmed pregnancy

Any other factors specifically not listed above but deemed patient unsuitable by the discretion of the investigators

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants apply Tapinarof 1% cream topically once daily for a 16-week open-label treatment period

16 weeks

4 visits (in-person)

Extension

Participants who do not achieve disease clearance continue treatment for up to 36 additional weeks or until clearance is achieved

Up to 36 weeks

Follow-up

Participants are monitored for sustained response and recurrence of keratoderma up to 52 weeks

52 weeks

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Tapinarof

Trial Overview The trial is testing Tapinarof, a natural compound used in psoriasis treatment, to see if it's effective and safe for treating palmoplantar keratoderma when applied daily as a topical medication.

How Is the Trial Designed?

Group I: Tapinarof Drug Treatment Experimental Treatment 1 Intervention

Subjects in this arm will apply Tapinarof 1% cream topically once daily for a 16-week open-label treatment period. Participants who achieve disease clearance after 16 weeks may discontinue treatment and will be monitored for sustained response up to 52 weeks. Those who do not achieve clearance will continue the treatment during an extension period for up to 36 additional weeks or until clearance is achieved, whichever comes first. Regular follow-up visits will assess the duration of disease clearance and monitor for any potential recurrence of keratoderma.

Tapinarof is already approved in United States for the following indications:

Approved in United States as Vtama for:

• Plaque psoriasis in adults
• Atopic dermatitis in adults and pediatric patients 2 years of age and older

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Dermavant Sciences, Inc.

Industry Sponsor

Trials

9

Recruited

1,800+

Published Research Related to This Trial

Tapinarof (VTAMA®) 1% cream is an effective new treatment for plaque psoriasis, showing significant improvement in 35.4% to 40.2% of patients compared to only 6.0% to 6.3% in the placebo group over 12 weeks in phase 3 trials.

The mechanism of action involves tapinarof activating aryl hydrocarbon receptors, which help regulate immune response and maintain skin health, although some patients experienced mild adverse effects like folliculitis and headaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

VTAMA® (Tapinarof) Cream* for Plaque Psoriasis. Gupta, AK., Ravi, SP., Vincent, K., et al.[2022]

Tapinarof cream 1% is a topical treatment that acts as an aryl hydrocarbon receptor (AhR) agonist, which plays a role in regulating immune responses in the skin, and it has been approved in the USA for treating plaque psoriasis in adults.

The cream is also being studied for its effectiveness in treating atopic dermatitis, indicating its potential as a versatile treatment for various skin conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapinarof Cream 1%: First Approval. Keam, SJ.[2022]

Tapinarof 1% cream significantly improved psoriasis severity compared to a vehicle control, with 35.4% and 40.2% of patients achieving a clear or almost clear status after 12 weeks in two phase 3 trials involving 1,025 patients.

While tapinarof was effective, it was associated with local adverse events such as folliculitis and contact dermatitis, indicating the need for further studies to assess its long-term safety and efficacy compared to existing psoriasis treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. Lebwohl, MG., Stein Gold, L., Strober, B., et al.[2021]

Tapinarof, a new topical treatment for plaque psoriasis, has shown significant efficacy in two phase III trials, with 35.4%-40.2% of patients achieving a favorable response compared to only 6.0%-6.3% in the placebo group.

The treatment demonstrated a favorable safety profile over 40 weeks, with common side effects being mild (like folliculitis and contact dermatitis) and no new safety concerns identified, making it a promising alternative to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tapinarof for the treatment of psoriasis. Nogueira, S., Rodrigues, MA., Vender, R., et al.[2023]

Tapinarof, a new topical treatment for plaque psoriasis, was approved by the FDA in May 2022 and has shown proven efficacy and safety in clinical studies, making it a promising option for adults with this condition.

Unlike traditional topical corticosteroids, which can have adverse effects and limitations, tapinarof offers a novel mechanism of action by modulating the aryl hydrocarbon receptor, potentially improving patient care in managing psoriasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Tapinarof: Novel Topical Treatment for Plaque Psoriasis in Adults. Kalabalik-Hoganson, J., Nogid, A., Frey, K.[2023]

In a phase 2b study involving 247 adolescents and adults with atopic dermatitis, tapinarof cream (1% applied twice daily) significantly improved skin condition compared to a vehicle, with higher rates of improvement in Investigator Global Assessment and Eczema Area and Severity Index scores.

Most adverse events reported were mild or moderate, suggesting that tapinarof is a safe option for treating atopic dermatitis, although further larger studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and patient-reported outcomes from a phase 2b, randomized clinical trial of tapinarof cream for the treatment of adolescents and adults with atopic dermatitis. Paller, AS., Stein Gold, L., Soung, J., et al.[2021]

Tapinarof cream 1% was found to be well tolerated in 376 healthy adults across four phase 1 trials, showing only a slight potential for very mild cumulative skin irritation after 21 days of daily use.

The cream demonstrated no evidence of sensitization, photosensitization, or phototoxicity, indicating it is a safe option for treating conditions like psoriasis and potentially atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dermal Safety of Tapinarof Cream 1%: Results From 4 Phase 1 Trials. Jett, J., McLaughlin, M., Wilson, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06561321

Study to Evaluate the Safety and Efficacy of Tapinarof in ... Daily topical Tapinarof use will stop disease advancement and improve the quality of life in patients with palmoplantar keratoderma, through its AhR & NRF2 ...

2. withpower.com withpower.com/trial/phase-2-keratoderma-palmoplantar-7-2024-2f3bf

Tapinarof for Palmoplantar Keratoderma Tapinarof (VTAMA®) 1% cream is an effective new treatment for plaque psoriasis, showing significant improvement in 35.4% to 40.2% of patients compared to only ...

3. app.trialscreen.org app.trialscreen.org/trials/phase-2-to-evaluate-safety-efficacy-tapinarof-adults-palmoplantar-keratoderma-trial-nct06561321

Study to Evaluate the Safety and Efficacy of Tapinarof in ... Participants may experience an improvement in their palmoplantar keratoderma condition if the treatment is effective. They will also contribute to the ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10882012/

Treatment of palmoplantar keratoderma in a patient with ... This case describes improvement in PPK of the soles in a patient with ichthyosis using topical tapinarof. Tapinarof has a novel mechanism of action as an aryl ...

5. dermatologytimes.com dermatologytimes.com/view/benvitimod-is-safe-and-effective-for-palmoplantar-pustulosis-new-study-finds

Benvitimod is Safe for Palmoplantar Pustulosis, New Study ... By week 8, 70% of patients achieved a PPPASI-50 response, with minimal relapse and limited adverse effects reported. The study suggests ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11484133/

Tapinarof cream for the treatment of plaque psoriasis Tapinarof was generally safe for up to 52 weeks of treatment. The most common AEs were folliculitis and contact dermatitis, both of which were ...

7. clinconnect.io clinconnect.io/trials/NCT06561321

Study to Evaluate the Safety and Efficacy of Tapinarof This clinical trial is looking at how safe and effective a medication called tapinarof is for adults with palmoplantar keratoderma, a condition that causes ...