Topical Ruxolitinib Cream for Hidradenitis Suppurativa

Overseen By Andrea Zaenglein, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Milton S. Hershey Medical Center

Must not be taking: JAK inhibitors, Systemic corticosteroids

Disqualifiers: Active skin disease, Pregnancy, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

24 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

You may need to stop some medications, but others can be continued if they have been at a stable dose for a certain period. For example, biologic medications can be continued if stable for 6 months, oral antibiotics for 28 days, hormone-based therapy for 4 months, and oral retinoids for 90 days. However, other topical therapies must be stopped 14 days before the study starts.

What data supports the effectiveness of the drug Ruxolitinib 1.5% Cream for treating hidradenitis suppurativa?

Ruxolitinib cream has shown effectiveness in treating atopic dermatitis, a skin condition, by reducing itchiness and improving skin condition. While it hasn't been specifically studied for hidradenitis suppurativa, its success in treating similar inflammatory skin conditions suggests it might be beneficial. ^{1 2 3 4 5}

Is topical Ruxolitinib cream safe for use in humans?

Topical Ruxolitinib cream has been well tolerated in studies for conditions like atopic dermatitis, with a safety profile similar to a placebo cream and only infrequent mild skin reactions like stinging or burning. It has minimal absorption into the body, which supports its safety compared to oral forms of the medication. ^{2 3 5 6 7}

How is Ruxolitinib cream different from other drugs for hidradenitis suppurativa?

Ruxolitinib cream is unique because it is a topical treatment, meaning it is applied directly to the skin, unlike other drugs for hidradenitis suppurativa that are usually injected or taken orally. This cream works by targeting specific pathways involved in inflammation, potentially offering a new approach for managing this condition. ^{1 8 9 10 11}

What is the purpose of this trial?

Investigators hypothesize that ruxolitinib 1.5% cream is an effective therapy for HS participants through inhibition of inflammatory activity. Investigators aim to: * Demonstrate the clinical efficacy of ruxolitinib 1.5% cream in decreasing the clinical disease activity after 16 weeks of treatment. * Investigate the impact of ruxolitinib 1.5% cream on skin inflammation through translational analyses of skin biopsy samples.

Eligibility Criteria

This trial is for individuals aged 12 or older with Hidradenitis Suppurativa (HS), specifically Hurley Stage I or II. Participants must have active HS lesions in at least one area, a minimum of 3 inflammatory lesions, and a diagnosis of HS for at least 3 months. They should not have other skin conditions that could affect the study, be pregnant or lactating, and must agree to use contraception during the study.

Inclusion Criteria

My current medications have been stable and won't change during the study.

I had surgery in the treatment area more than 3 months ago.

I have Hidradenitis suppurativa at an early or moderate stage.

Exclusion Criteria

Does not have reliable internet access for weekly electronic surveys

I do not have any active skin conditions that could affect HS assessment.

Pregnant (or considering becoming pregnant) or lactating females

Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive topical Ruxolitinib 1.5% cream, twice daily for 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ruxolitinib 1.5% Cream

Trial Overview The trial tests Ruxolitinib 1.5% cream's effectiveness on HS by reducing inflammation over a period of 16 weeks. It also examines how this topical treatment affects skin inflammation through analysis of biopsy samples from participants.

Participant Groups

Group I: Open-label Experimental Treatment 1 Intervention

Topical Ruxolitinib 1.5% Cream, twice daily for 16 weeks

Ruxolitinib 1.5% Cream is already approved in United States, European Union for the following indications:

Approved in United States as Opzelura for:

• Atopic dermatitis
• Nonsegmental vitiligo

Approved in European Union as Opzelura for:

• Atopic dermatitis
• Nonsegmental vitiligo

Who Is Running the Clinical Trial?

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

Secukinumab, an IL-17A inhibitor, has shown promising efficacy in treating hidradenitis suppurativa, as demonstrated in the phase III SUNSHINE and SUNRISE clinical trials.

Unlike the currently FDA-approved treatment for hidradenitis suppurativa, adalimumab, which targets TNF-α, secukinumab offers a different mechanism of action that may benefit patients with this inflammatory skin condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Secukinumab in the treatment of hidradenitis suppurativa. Snyder, CL., Gibson, RS., Porter, ML., et al.[2023]

Ruxolitinib cream 1.5% significantly improved disease severity, itching, and sleep disturbance in patients aged 12 and older with mild to moderate atopic dermatitis after 8 weeks of treatment, and continued to control symptoms for an additional 44 weeks when applied as needed.

The cream was well tolerated, with a safety profile similar to that of a placebo, and infrequent local side effects, making it a promising alternative to traditional treatments like corticosteroids for managing atopic dermatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib Cream 1.5%: A Review in Mild to Moderate Atopic Dermatitis. Hoy, SM.[2023]

Ruxolitinib cream, a topical treatment for atopic dermatitis, was found to be generally well tolerated in a study of 41 patients aged 12 to 65, with only 31.7% experiencing treatment-emergent adverse events, and only 9.8% reporting treatment-related adverse events.

The cream demonstrated high efficacy, with 94.6% of patients achieving at least a 75% improvement in their eczema severity after 56 days of treatment, while the mean plasma concentration of the drug remained well below levels that could cause harmful effects on bone marrow.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. Bissonnette, R., Call, RS., Raoof, T., et al.[2022]

In two phase 3 trials involving 1249 patients with atopic dermatitis, ruxolitinib cream showed rapid and significant reductions in itch, with over 16% of patients experiencing a 2-point reduction within 12 hours compared to only 6.9% with the vehicle cream.

By Day 2, a greater percentage of patients using ruxolitinib cream achieved a 4-point reduction in itch severity, with sustained improvements observed over the 8-week treatment period, indicating both efficacy and a quick onset of action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. Blauvelt, A., Kircik, L., Papp, KA., et al.[2023]

In two phase 3 studies involving 1249 patients with atopic dermatitis, ruxolitinib cream significantly improved treatment outcomes compared to a vehicle cream, with 93.4% of patients using the 0.75% formulation and 90.9% using the 1.5% formulation achieving clinically meaningful responses by week 8.

Patients who continued using ruxolitinib cream beyond 8 weeks showed progressive improvements, with over half achieving treatment success by week 52, indicating that extended therapy can provide additional benefits and that the cream was well tolerated throughout the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy. Simpson, EL., Kircik, L., Blauvelt, A., et al.[2023]

Ruxolitinib, a JAK1 and JAK2 inhibitor used for myelofibrosis and polycythemia vera, showed no carcinogenic potential in long-term studies with Tg.rasH2 mice and Sprague-Dawley rats, indicating it does not increase cancer risk.

Despite some pharmacological effects like lymphoid depletion and inflammation, ruxolitinib did not affect survival rates or increase neoplastic findings, suggesting it is safe for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. Shuey, DL., Oliver, J., Zhou, G., et al.[2021]

Topical ruxolitinib has been shown to improve various dermatological conditions, including atopic dermatitis, vitiligo, psoriasis, and lichen planus, based on a review of 24 studies involving 2618 patients.

The safety profile of topical ruxolitinib is favorable, with minimal bioavailability and low rates of mild-to-moderate side effects, making it a more tolerable option compared to systemic Janus kinase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Utilization of Topical Ruxolitinib in Dermatology: A Review. Kashetsky, N., Turchin, I.[2023]

Secukinumab, an anti-IL-17A monoclonal antibody, has been approved for treating moderate to severe Hidradenitis suppurativa (HS), marking a significant advancement in therapy for this chronic inflammatory skin disorder affecting 0.4% to 2.5% of the global population.

Clinical trials have demonstrated the safety and efficacy of secukinumab in HS, providing a new treatment option alongside the previously approved adalimumab, which targets a different inflammatory pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa. Sabat, R., Gudjonsson, JE., Brembilla, NC., et al.[2023]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that causes painful lesions, and while there have been advancements in treatment, effective therapies are still needed.

Adalimumab is currently the only FDA-approved treatment for HS, but new biologics targeting specific inflammatory pathways are being tested in clinical trials, showing promise for future therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological development in hidradenitis suppurativa. Matusiak, Ł., Jemec, GB., Szepietowski, JC.[2020]

In a review of 12 randomized controlled trials involving 2915 patients, adalimumab and bimekizumab were found to be effective treatments for moderate-to-severe hidradenitis suppurativa, showing significant improvement in clinical response compared to placebo at 12-16 weeks.

All evaluated biologics, including adalimumab, bimekizumab, and secukinumab, demonstrated similar safety profiles with no increased risk of adverse effects compared to placebo, making them viable options for patients with refractory hidradenitis suppurativa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis. Tsai, YC., Hung, CY., Tsai, TF.[2023]

A systematic review of 34 publications involving 105 patients with hidradenitis suppurativa (HS) found that TNF-alpha inhibitors, particularly infliximab, led to positive treatment outcomes in 90% of cases, indicating their potential efficacy in managing this challenging skin condition.

While side effects were reported in 8 out of 105 patients, they were similar to those seen in other studies with TNF-alpha inhibitors, suggesting a manageable safety profile; however, the need for more standardized reporting and randomized controlled trials is emphasized to better understand long-term effects and optimal treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors. Haslund, P., Lee, RA., Jemec, GB.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

Secukinumab in the treatment of hidradenitis suppurativa. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Ruxolitinib Cream 1.5%: A Review in Mild to Moderate Atopic Dermatitis. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

A Maximum-Use Trial of Ruxolitinib Cream in Adolescents and Adults with Atopic Dermatitis. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Clinically relevant improvements in adults and adolescents with atopic dermatitis who did not achieve Investigator's Global Assessment treatment success following 8 weeks of ruxolitinib cream monotherapy. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Results from oral gavage carcinogenicity studies of ruxolitinib in Tg.rasH2 mice and Sprague-Dawley (Crl:CD) rats. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Utilization of Topical Ruxolitinib in Dermatology: A Review. [2023]

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

Biology of Interleukin-17 and Novel Therapies for Hidradenitis Suppurativa. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacological development in hidradenitis suppurativa. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Biologics and Small Molecules for Moderate-to-Severe Hidradenitis Suppurativa: A Systematic Review and Network Meta-Analysis. [2023]

11. Sweden pubmed.ncbi.nlm.nih.gov

Treatment of hidradenitis suppurativa with tumour necrosis factor-alpha inhibitors. [2018]