Tapinarof for Cutaneous Lupus

Overseen By Dermatology CTU

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Northwestern University

Must not be taking: Corticosteroids, Calcineurin inhibitors, Anifrolumab, others

Disqualifiers: Pregnancy, Breast-feeding, Active infections, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

10 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

You may need to stop certain medications before joining the trial. Specifically, you cannot use certain topical treatments on the lupus lesions within 1 to 4 weeks before starting the study drug, and you should not start new systemic immunosuppressive drugs within 12 weeks of starting the trial. If you're already on these drugs, your dosage should be stable for at least 4 weeks before the trial begins.

What makes the drug Tapinarof unique for treating cutaneous lupus?

Tapinarof is unique because it is a non-steroidal topical cream that works by activating aryl hydrocarbon receptors, which help regulate the immune response and maintain skin health. This mechanism is different from many existing treatments for skin conditions, which often involve steroids or systemic medications. ^{1 2 3 4 5}

What is the purpose of this trial?

The investigators hypothesize that topical application of Tapinarof, an FDA-approved topical Aryl hydrocarbon receptor (AHR) agonist for the treatment of plaque psoriasis, would inhibit lupus-causing T cells and lead to improvement of cutaneous lupus lesions. To test this hypothesis, the investigators will perform a prospective, interventional clinical trial in patients with chronic and/or subacute cutaneous lupus. This trial will include outcomes analyzing the change in cutaneous lupus lesions using standardized assessments, but also analyze pre- and post-treatment skin and blood immune parameters to elucidate the immune effects and changes in lupus as a result of topical AHR agonist application. The goals are to 1) identify if topical AHR agonism leads to improvement in cutaneous lupus, and 2) examine the immunopathology of cutaneous lupus and its alteration with topical AHR agonist treatment.

Research Team

Paras Vakharia

Principal Investigator

Northwestern University

Eligibility Criteria

This trial is for patients with chronic or subacute cutaneous lupus erythematosus. Participants should have persistent skin lesions characteristic of the condition. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be excluded based on factors like other medical conditions or treatments that could interfere with the study.

Inclusion Criteria

I have been diagnosed with chronic or subacute cutaneous lupus.

I have a skin lupus lesion larger than 1cm with a moderate to severe score.

Exclusion Criteria

Patients who are pregnant or breast-feeding

I currently have an active infection.

History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the study drug

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive topical Tapinarof treatment for cutaneous lupus

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Tapinarof

Trial Overview The trial is testing Tapinarof, a medication approved for plaque psoriasis, to see if it can improve skin lesions in cutaneous lupus by inhibiting harmful T cells. It's an interventional study where changes in lesions will be measured before and after treatment, along with immune system analysis.

Participant Groups

Group I: Tapinarof Treatment Experimental Treatment 1 Intervention

CLE participants treated with tapinarof

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?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

Findings from Research

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&#174; (Tapinarof) Cream* for Plaque Psoriasis. Gupta, AK., Ravi, SP., Vincent, K., et al.[2022]

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]

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]

Benvitimod (Tapinarof) effectively reduces the excessive proliferation of keratinocytes in psoriasis by inhibiting the MCM6 protein, which is crucial for cell replication, as demonstrated in both in vitro studies with HaCaT cells and in vivo studies using an imiquimod-induced mouse model.

The mechanism of action involves the inhibition of the JAK/STAT3 signaling pathway, specifically by reducing the activation of p-JAK1 and p-JAK2, leading to decreased STAT3 activation and ultimately lowering keratinocyte proliferation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benvitimod inhibits MCM6-meditated proliferation of keratinocytes by regulating the JAK/STAT3 pathway. Cai, Z., Zeng, Y., Shi, X., et al.[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]

References

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

VTAMA&#174; (Tapinarof) Cream* for Plaque Psoriasis. [2022]

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

Dermal Safety of Tapinarof Cream 1%: Results From 4 Phase 1 Trials. [2022]

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

Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Benvitimod inhibits MCM6-meditated proliferation of keratinocytes by regulating the JAK/STAT3 pathway. [2023]

5. United States 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. [2021]