Upadacitinib for Hidradenitis Suppurativa

(Step-Up HS Trial)

Recruiting at 395 trial locations

Overseen By ABBVIE CALL CENTER

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Anti-TNF biologics

Must not be taking: Cell-depleting therapies

Disqualifiers: Active skin disease, Investigational drugs, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

1328 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of the drug upadacitinib for treating hidradenitis suppurativa (HS), a painful skin condition that causes lesions in areas like the underarms and groin. The study targets individuals with moderate to severe HS who haven't improved with certain other medications. Participants will receive either upadacitinib or a placebo over several months, with researchers closely monitoring their progress. Those who have had HS for at least six months and have tried other treatments without success might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting. You must stop using prescription topical therapies for HS and systemic antibiotics at least 14 days before the trial begins. Other investigational drugs and certain cell-depleting therapies must also be stopped before participating.

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

Studies have shown that upadacitinib is generally well-tolerated by patients with inflammatory conditions like rheumatoid arthritis and atopic dermatitis. As an approved medication for these conditions, its safety is well-understood. Research indicates that while some patients might experience side effects like infections, these are usually manageable and can vary in severity.

Early results from a study on hidradenitis suppurativa (HS) suggest that upadacitinib can help reduce symptoms. Although health authorities have not fully reviewed its safety specifically for HS, its use in other conditions provides some reassurance about its safety. Participants in past studies often reported mild to moderate side effects, with serious side effects being rare.

Overall, while researchers continue to study upadacitinib for HS, its previous use in other conditions and ongoing monitoring in trials contribute to understanding its safety in people. ^{1 2 3 4 5}

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

Upadacitinib is unique because it targets the JAK1 pathway, which plays a role in the inflammatory process of hidradenitis suppurativa. Most treatments for this condition, like antibiotics or biologics such as adalimumab, focus on reducing inflammation or infection after it has occurred. Upadacitinib, however, works at a different level by directly inhibiting specific enzymes involved in triggering inflammation, potentially offering a more targeted approach. Researchers are excited about its potential to provide relief with possibly fewer side effects and improved efficacy in controlling this chronic skin condition.

What evidence suggests that upadacitinib might be an effective treatment for hidradenitis suppurativa?

Research shows that upadacitinib, which participants in this trial may receive, can help reduce symptoms of hidradenitis suppurativa (HS). In earlier studies, patients experienced at least a 50% decrease in painful lumps and bumps, without an increase in abscesses or draining tunnels. This results in fewer painful skin issues for those with moderate to severe HS. Upadacitinib has already proven effective for other inflammatory conditions like rheumatoid arthritis and eczema, suggesting it might also benefit those with HS. These findings indicate that upadacitinib could be a good option for managing HS symptoms. ^{2 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults and adolescents with moderate to severe Hidradenitis Suppurativa (HS) who haven't improved on anti-TNF therapy can join. They must have HS in at least two areas, been diagnosed for over 6 months, and meet specific lesion counts. Excluded are those with other active skin diseases or recent use of certain drugs.

Inclusion Criteria

My skin condition affects at least one area and is moderate to severe.

I have tried at least one TNF inhibitor for HS for 12 weeks or a non-TNF biologic for 16 weeks without success, or I couldn't tolerate it.

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

Exclusion Criteria

I have no active skin conditions or infections that could affect my HS assessment.

I haven't had cell-depleting therapies like rituximab in the last year or until my B cell count normalized.

I haven't taken antibiotics for HS or any chronic inflammation in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Period 1

Participants receive oral tablets of upadacitinib or placebo once daily

16 weeks

Regular outpatient visits

Treatment Period 2

Participants continue treatment based on response in Period 1

20 weeks

Regular outpatient visits

Long-Term Extension

Eligible participants continue to receive upadacitinib or placebo

68 weeks

Regular outpatient visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Upadacitinib

Trial Overview The trial tests Upadacitinib's effectiveness against HS compared to a placebo. It's double-blinded, so participants won't know if they're getting the drug or placebo. The study has three periods: initial treatment phase, adjustment based on results, and long-term extension for up to 68 weeks.

How Is the Trial Designed?

Group I: Period 3: Long-Term Extension Experimental Treatment 2 Interventions

Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days.

Group II: Period 2: Group 6 - Placebo Experimental Treatment 1 Intervention

Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive placebo once daily for 20 weeks.

Group III: Period 2: Group 5 - Upadacitinib Dose B Experimental Treatment 1 Intervention

Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose B once daily for 20 weeks.

Group IV: Period 2: Group 4 - Upadacitinib Dose A Experimental Treatment 1 Intervention

Participants who were randomized to upadacitinib Dose A in Period 1 who achieve HiSCR 50 (CR) at Week 16 will receive upadacitinib Dose A once daily for 20 weeks.

Group V: Period 2: Group 3 - Upadacitinib Dose A Experimental Treatment 1 Intervention

Participants who were randomized to upadacitinib Dose A in Period 1 who did not achieve HiSCR 50 (CNR) at Week 16 will continue to receive upadacitinib Dose A once daily for 20 weeks.

Group VI: Period 2: Group 1 - Upadacitinib Dose A Experimental Treatment 1 Intervention

Participants who were randomized to placebo in Period 1 who did not achieve HiSCR 50 (clinical non-responder, CNR) at Week 16 will receive Upadacitinib Dose A once daily for 20 weeks.

Group VII: Period 1: Upadacitinib Dose A Experimental Treatment 1 Intervention

Participants will receive Upadicitinib Dose A once daily for 16 weeks.

Group VIII: Period 1: Placebo Placebo Group 1 Intervention

Participants will receive Placebo once daily for 16 weeks.

Group IX: Period 2: Group 2 - Placebo Placebo Group 1 Intervention

Participants who were randomized to placebo in Period 1 who achieve HiSCR 50 (clinical responder, CR) at Week 16 will continue to receive placebo once daily for 20 weeks.

Upadacitinib is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in United States as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis
• Ulcerative colitis
• Crohn's disease

Approved in Canada as Rinvoq for:

• Rheumatoid arthritis
• Psoriatic arthritis
• Atopic dermatitis
• Ankylosing spondylitis

Who Is Running the Clinical Trial?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Published Research Related to This Trial

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]

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]

Adalimumab, a treatment for Crohn's disease, has recently been approved for hidradenitis suppurativa, but in this case, it paradoxically triggered the onset of hidradenitis suppurativa in a 40-year-old woman.

This case highlights the potential for unexpected side effects of medications, even those that are effective for other conditions, emphasizing the need for careful monitoring in patients receiving adalimumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hidradenitis suppurativa in Crohn's disease during adalimumab therapy: a paradox? Martina, E., Campanati, A., Giuliodori, K., et al.[2019]

In a case series involving 6 patients with treatment-resistant inflammatory skin conditions, the JAK inhibitors upadacitinib and tofacitinib showed promising clinical outcomes, including symptom resolution and reduced flares in conditions like dermatomyositis and hidradenitis suppurativa.

These findings suggest that JAK inhibitors may serve as effective off-label treatments for various inflammatory cutaneous disorders, warranting further research with larger patient groups to confirm their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases. Agarwal, A., Diaz, A., Al-Dehneem, R., et al.[2023]

Upadacitinib, a selective JAK1 inhibitor, demonstrated an oral bioavailability of approximately 80% for its extended-release formulation compared to the immediate-release version, based on a pharmacokinetic analysis of 11,658 plasma concentrations from 1,145 subjects across multiple studies.

The study found that while certain factors like sex and renal function can affect drug levels in the body, these variations are not expected to lead to clinically significant changes in the drug's effectiveness or safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Upadacitinib in Healthy Subjects and Subjects With Rheumatoid Arthritis, Crohn's Disease, Ulcerative Colitis, or Atopic Dermatitis: Population Analyses of Phase 1 and 2 Clinical Trials. Nader, A., Stodtmann, S., Friedel, A., et al.[2021]

Citations

1. jaad.org jaad.org/article/S0190-9622(25)00190-2/fulltext

Improvements in moderate-to-severe hidradenitis ... The primary endpoint was ≥50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count.

2. news.abbvie.com news.abbvie.com/2023-07-24-AbbVie-Advances-Immunology-Pipeline-with-First-Patient-Dosed-in-Global-Phase-3-Trial-of-Upadacitinib-RINVOQ-R-in-Hidradenitis-Suppurativa

AbbVie Advances Immunology Pipeline with First Patient ... First registered, randomized Phase 3 trial in hidradenitis suppurativa (HS) evaluating the efficacy and safety of upadacitinib (RINVOQ®) in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05889182

NCT05889182 | A Study to Assess Change in Disease ... This study will assess how safe and effective upadacitinib is in treating adult and adolescent participants with moderate to severe HS who have failed to ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39909350/

Improvements in moderate-to-severe hidradenitis ... The primary endpoint was ≥50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0190962225001902

Improvements in moderate-to-severe hidradenitis ... Treatment with upadacitinib demonstrated improved and durable lesion and pain control in adults with moderate-to-severe HS. An ongoing phase 3 trial is ...

6. rinvoqhcp.com rinvoqhcp.com/dermatology/safety

RINVOQ® (upadacitinib) Safety Data Long-term safety data through November 24, 2020 (64%-66% of patients had >1 year of exposure to RINVOQ; total exposure=2788 PY).

7. rinvoqhcp.com rinvoqhcp.com/safety

RINVOQ® (upadacitinib) Safety Profile Patients treated with RINVOQ are at increased risk for developing infections that may lead to hospitalization or death.