Povorcitinib for Hidradenitis Suppurativa

(STOP-HS2 Trial)

Not currently recruiting at 124 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Povorcitinib to determine its safety and effectiveness for individuals with moderate to severe Hidradenitis Suppurativa (HS), a skin condition that causes painful bumps and abscesses. Over about a year, participants will receive varying doses of the medication or a placebo (a dummy treatment with no active drug) initially, to compare results. Those who have had HS for at least 3 months, with lesions in two or more areas, and have not responded well to other treatments might be suitable for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially bringing a new treatment to market.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that povorcitinib has been safe for people with hidradenitis suppurativa (HS) in past studies. It works by blocking certain proteins that cause swelling and irritation. Studies found that taking povorcitinib in various doses did not lead to more side effects than usual. This indicates that participants did not experience more issues than those taking a placebo (a fake treatment). Reports also showed that it helped reduce symptoms like abscesses and bumps under the skin. The evidence suggests that povorcitinib is generally well-tolerated by people with HS. ^{1 2 3 4 5}

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

Povorcitinib is unique because it targets a specific pathway involved in the inflammation process of hidradenitis suppurativa, offering a new approach compared to current treatments like antibiotics or TNF inhibitors. Unlike standard therapies that often focus on broadly suppressing the immune system, Povorcitinib specifically inhibits the Janus kinase (JAK) pathway, potentially reducing symptoms with more precision. This targeted action could lead to improved outcomes and fewer side effects, making researchers hopeful about its potential to provide better relief for patients suffering from this challenging condition.

What evidence suggests that Povorcitinib could be an effective treatment for Hidradenitis Suppurativa?

Research shows that povorcitinib may help treat hidradenitis suppurativa (HS), a skin condition that causes painful lumps. In earlier studies, many patients who took povorcitinib daily experienced improvements compared to those who took a placebo. This trial will test different doses of povorcitinib, with some participants receiving Povorcitinib Dose A and others receiving Povorcitinib Dose B. Additionally, a placebo group will initially receive a placebo before switching to povorcitinib. In those studies, the treatment effectively reduced common HS symptoms like abscesses, swollen lumps, and draining tunnels. Importantly, these benefits came without more side effects, making it a safer option for many. Overall, evidence suggests povorcitinib could be an effective pill treatment for people with moderate to severe HS. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

Citations

1. investor.incyte.com investor.incyte.com/news-releases/news-release-details/incyte-announces-new-24-week-phase-3-data-stop-hs-clinical-trial

Incyte Announces New 24-Week Phase 3 Data from the ... A significantly higher proportion of patients treated with povorcitinib once daily (QD) versus placebo achieved Hidradenitis Suppurativa ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871805/

Efficacy and safety of the oral Janus kinase 1 inhibitor ... Povorcitinib demonstrated efficacy in HS, with no evidence of increased incidence of adverse events among doses.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04476043

Study Details | NCT04476043 | To Assess the Efficacy and ... To evaluate the efficacy and safety of INCB054707 in participants with hidradenitis suppurativa over a 16-week placebo-controlled treatment period followed ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0190962223030372

Efficacy and safety of the oral Janus kinase 1 inhibitor ... Povorcitinib, an oral, selective Janus kinase 1 inhibitor, reduced abscess, inflammatory nodule, and draining tunnel counts compared with placebo and was ...

5. rheumatologyadvisor.com rheumatologyadvisor.com/news/povorcitinib-improves-hidradenitis-suppurativa-in-two-phase-3-trials/

Povorcitinib Improves Hidradenitis Suppurativa in Two ... “The positive phase 3 data highlight the potential of povorcitinib as an effective oral treatment option for people living with HS.” According ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06212999

NCT06212999 | A Study to Evaluate the Long-Term Safety ... The purpose of this study is to evaluate long-term safety and efficacy of povorcitinib in participants with moderate to severe hidradenitis suppurativa who ...