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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Tapinarof, a topical cream already approved for plaque psoriasis, can improve skin lesions in individuals with cutaneous lupus. Researchers seek to discover if the cream can calm the immune cells responsible for lupus skin issues. The trial will also examine the treatment's effects on the immune system in both the skin and blood. Individuals diagnosed with chronic or subacute cutaneous lupus and possessing at least one active skin lesion may be suitable candidates for this trial. As an Early Phase 1 trial, this research focuses on understanding the treatment's effects in people, offering participants an opportunity to contribute to groundbreaking research.

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.

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

Research has shown that tapinarof, a cream for treating psoriasis, is safe and gentle on the skin. In earlier studies, when applied to sensitive skin areas, only a few participants reported mild irritation. Users found it gentle, even on delicate areas like the face and neck.

In a large safety study, 763 participants used tapinarof for up to 40 weeks without major issues. The FDA has approved this cream for psoriasis, indicating it is generally safe for skin use. While this trial examines its use for cutaneous lupus, the existing safety data from psoriasis treatments is encouraging. ^{1 2 3 4 5}

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

Unlike the standard treatments for cutaneous lupus, which often involve corticosteroids or antimalarial drugs, tapinarof is a topical treatment that works by modulating the aryl hydrocarbon receptor (AhR) pathway. This new mechanism of action is significant because it targets an entirely different pathway in the skin, potentially offering benefits with fewer side effects. Researchers are excited about tapinarof because it provides a novel approach to managing symptoms and could offer an alternative for patients who do not respond well to existing treatments.

What evidence suggests that Tapinarof might be an effective treatment for cutaneous lupus?

Research has shown that Tapinarof, a topical cream, may help treat conditions like cutaneous lupus. This trial will administer Tapinarof to participants to evaluate its effectiveness. One study found that using Tapinarof 1% cream helped individuals with discoid lupus erythematosus, a type of cutaneous lupus, improve quickly and maintain those improvements. Another study found that Tapinarof reduced lupus symptoms by addressing immune system issues that cause the disease. The cream targets a specific part of the skin, potentially reducing inflammation and improving skin conditions. While more research is needed, these early results suggest Tapinarof could be effective for cutaneous lupus. ^{4 6 7 8 9}

Who Is on the Research Team?

Paras Vakharia

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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]

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]

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]

Citations

1. ctv.veeva.com ctv.veeva.com/study/tapinarof-for-cutaneous-lupus-erythematosus

Tapinarof for Cutaneous Lupus Erythematosus This trial will include outcomes analyzing the change in cutaneous lupus ... Efficacy of Topical Tacrolimus in Different Subtypes With Cutaneous ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11566309/

Successful treatment of discoid lupus erythematosus with ... To our knowledge, this was the first report of rapid successful treatment and sustained disease remission of DLE with tapinarof 1% cream. DLE often relies on ...

3. synapse.patsnap.com synapse.patsnap.com/drug/fd3b716a779844eb99352d1133fa0ee5

Benvitimod - Drug Targets, Indications, Patents Investigators reported improvement from pretreatment baseline with no-to-minimal irritation (dryness/erythema/peeling) from first Tapinarof application through ...

4. researchgate.net researchgate.net/publication/371584940_AhR_agonist_tapinarof_ameliorates_lupus_autoimmunity_by_suppressing_Tfh_cell_differentiation_via_regulation_of_the_JAK2-STAT3_signaling_pathway/download

AhR agonist tapinarof ameliorates lupus autoimmunity ... Results: We found that tapinarof treatment ameliorated lupus phenotypes, including splenomegaly, lymph node enlargement, kidney damages, immune complex ...

5. go.drugbank.com go.drugbank.com/drugs/DB06083

Tapinarof: Uses, Interactions, Mechanism of Action Tapinarof is a novel, first-in-class, small-molecule AhR agonist that is indicated for the treatment of adult psoriasis.

6. vtamahcp.com vtamahcp.com/atopic-dermatitis/safety-profile/

Safety - VTAMA® (tapinarof) cream, 1% (50) Safe and well tolerated, even on sensitive skin areas. There are no label restrictions on topical use. No-to-minimal irritation, even on affected sensitive ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2022/215272s000lbl.pdf

VTAMA (tapinarof) cream, for topical use - accessdata.fda.gov In an open label safety trial (PSOARING 3), 763 subjects were treated for up to an additional 40 weeks after completing PSOARING 1 or PSOARING 2. In addition to ...

8. vtamahcp.com vtamahcp.com/plaque-psoriasis/safety-profile/

Safety Profile - VTAMA® (tapinarof) cream, 1% (50) In the pivotal trials, the tolerability scores were mild when assessed in sensitive skin areas such as the face, neck, intertriginous areas, inframammary areas, ...

9. medcentral.com medcentral.com/drugs/monograph/184219-322028/tapinarof-topical

Tapinarof: uses, dosing, warnings, adverse events, ... Safety and efficacy of tapinarof for this use are based on the results of two phase 3 trials, which enrolled patients with mild-to-severe plaque psoriasis, as ...