Povorcitinib for Hidradenitis Suppurativa

(STOP-HS2 Trial)

Recruiting at 112 trial locations

Overseen By Incyte Corporation Call Center (US)

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Incyte Corporation

Must not be taking: JAK inhibitors

Disqualifiers: Pregnancy, Cardiovascular diseases, Infections, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

619 Participants Needed

Trial Summary

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

The trial protocol does not specify whether you need to stop taking your current medications. However, you must agree not to use certain topical antiseptics on the areas affected by HS lesions during the placebo-controlled period.

Is Povorcitinib safe for humans?

In two phase 2 studies, Povorcitinib, an investigational treatment for hidradenitis suppurativa, was tested in humans and showed changes in gene and protein markers related to inflammation, suggesting it may be safe, but specific safety outcomes were not detailed. ^{1 2 3 4 5}

How is the drug Povorcitinib unique in treating Hidradenitis Suppurativa?

Povorcitinib is unique because it is an oral drug that specifically targets the JAK1 pathway, which is involved in the inflammation seen in Hidradenitis Suppurativa. This mechanism of action is different from other treatments like TNF-α inhibitors or IL-17 inhibitors, offering a novel approach to modulating the disease's underlying pathology. ^{1 5 6 7 8}

What is the purpose of this trial?

This trial is testing a medication called Povorcitinib to see if it helps people with moderate to severe Hidradenitis Suppurativa (HS). HS is a skin condition that causes painful lumps and sores. The medication aims to reduce inflammation and improve symptoms over several months, with additional follow-up.

Eligibility Criteria

Adults over 18 with moderate to severe Hidradenitis Suppurativa (HS) for at least 3 months, having lesions in two or more areas and not responding well to conventional treatments can join. They must avoid using certain antiseptics and agree to prevent pregnancy. Excluded are those with a high number of draining tunnels, serious heart issues, blood disorders, active infections like TB or HIV, or past JAK inhibitor treatment failures.

Inclusion Criteria

I have HS and treatments so far haven't worked or I can't take them.

I have HS lesions in at least two different body areas.

I agree not to use specific skin cleaners on my HS spots during the study.

Exclusion Criteria

I have tried a JAK inhibitor for an inflammatory disease and it didn't work.

You have more than 20 draining tunnels during the screening or baseline visits.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Povorcitinib or placebo for 12 weeks to evaluate efficacy and safety

12 weeks

Extension

Participants who received placebo switch to Povorcitinib, and all participants continue treatment for an additional 42 weeks

42 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo
• Povorcitinib

Trial Overview The trial is testing Povorcitinib's effectiveness and safety against a placebo in treating HS over a period of 12 weeks initially. Participants will then enter an extension phase lasting another 42 weeks to gather additional data on the drug's performance.

Participant Groups

Group I: Povorcitinib Dose B Experimental Treatment 1 Intervention

Participants will receive Povorcitinib Dose B for 54 weeks.

Group II: Povorcitinib Dose A Experimental Treatment 1 Intervention

Participants will receive Povorcitinib Dose A for 54 weeks.

Group III: Placebo Placebo Group 1 Intervention

Participants will receive Placebo for 12 weeks, followed by Povorcitinib (Dose A or Dose B) for 42 weeks.

Who Is Running the Clinical Trial?

Incyte Corporation

Lead 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

IL-17 inhibitors, particularly secukinumab and brodalumab, show promising efficacy in treating hidradenitis suppurativa (HS), with response rates of 57.1% and 100% respectively among 128 patients studied.

These treatments can be effective for patients who do not respond to other therapies, highlighting the need for standardized outcome measures to improve future research and clinical practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review. Kashetsky, N., Mufti, A., Alabdulrazzaq, S., et al.[2022]

In patients with severe hidradenitis suppurativa (HS), there is an increase in specific inflammatory monocytes and a unique cytokine profile, indicating a complex immune response that could guide treatment choices.

Treatment with etanercept, a TNF blocker, showed clinical improvement linked to increased production of IL-1β and IL-17 in blood cells, suggesting that monitoring these cytokines could help predict treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. Kanni, T., Tzanetakou, V., Savva, A., et al.[2018]

In a study of patients with moderate to severe hidradenitis suppurativa (HS) treated with adalimumab (ADA) for at least 12 weeks, those carrying the common GGG haplotype had a significantly better response rate (71.8%) compared to those with minor frequency SNP haplotypes (50.0%).

Carriers of minor frequency SNP haplotypes showed a reduced decrease in inflammatory lesion count during treatment, suggesting that genetic factors may influence the efficacy of ADA in HS and could guide treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa. Argyropoulou, M., Trigoni, A., Kaffenberger, J., et al.[2023]

The BATMAN consortium is developing a comprehensive approach to understand hidradenitis suppurativa (HS) by identifying genetic variants and biological pathways linked to the disease, which could lead to personalized treatment options.

The project aims to create advanced cellular models and a smartphone application for remote patient monitoring, enhancing diagnosis and treatment strategies for HS through the integration of various scientific disciplines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Holistic health record for Hidradenitis suppurativa patients. Tricarico, PM., Moltrasio, C., Gradišek, A., et al.[2022]

In two phase 2 trials involving patients with moderate-to-severe hidradenitis suppurativa (HS), the oral JAK1-selective inhibitor povorcitinib showed significant transcriptomic changes, particularly at the 30 mg dose, indicating its potential efficacy in altering disease-related gene expression.

Povorcitinib treatment led to a dose-dependent downregulation of inflammatory markers and reversal of gene signatures associated with HS, suggesting that JAK1 inhibition could effectively target the underlying mechanisms of HS pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of Disease-Associated Pathways in Hidradenitis Suppurativa by the Janus Kinase 1 Inhibitor Povorcitinib: Transcriptomic and Proteomic Analyses of Two Phase 2 Studies. Liu, H., Santos, LL., Smith, SH.[2023]

JAK inhibitors, particularly INCB054707, upadacitinib, and tofacitinib, show promising efficacy and safety in treating hidradenitis suppurativa (HS), based on a review of 25 relevant studies.

Despite the encouraging results, the current evidence is limited due to the small number of studies and participants, highlighting the need for larger real-life studies to establish effective treatment options for HS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hidradenitis Suppurativa and JAK Inhibitors: A Review of the Published Literature. Martora, F., Scalvenzi, M., Ruggiero, A., et al.[2023]

A systematic review of 65 studies involving 459 patients indicates that TNF-α inhibitors, particularly infliximab, show moderate to good efficacy in treating hidradenitis suppurativa, with 82% of patients responding positively to infliximab, 76% to adalimumab, and 68% to etanercept.

Infliximab is recommended as the preferred treatment option due to its superior efficacy, while etanercept is discouraged, and adalimumab may be effective at higher doses, highlighting the need for careful consideration of treatment choices in severe cases of hidradenitis suppurativa.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The off-label treatment of severe hidradenitis suppurativa with TNF-α inhibitors: a systematic review. van Rappard, DC., Limpens, J., Mekkes, JR.[2018]

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]

References

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

Treatment Outcomes of IL-17 Inhibitors in Hidradenitis Suppurativa: A Systematic Review. [2022]

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

Compartmentalized Cytokine Responses in Hidradenitis Suppurativa. [2018]

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

Impact of Single Nucleotide Polymorphisms of the Promoter of the TNF Gene on Adalimumab Treatment Responses in Hidradenitis Suppurativa. [2023]

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

Holistic health record for Hidradenitis suppurativa patients. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Modulation of Disease-Associated Pathways in Hidradenitis Suppurativa by the Janus Kinase 1 Inhibitor Povorcitinib: Transcriptomic and Proteomic Analyses of Two Phase 2 Studies. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Hidradenitis Suppurativa and JAK Inhibitors: A Review of the Published Literature. [2023]

7. England pubmed.ncbi.nlm.nih.gov

The off-label treatment of severe hidradenitis suppurativa with TNF-α inhibitors: a systematic review. [2018]

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

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