Upadacitinib for Hidradenitis Suppurativa

(Step-Up HS Trial)

Recruiting at 318 trial locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if a daily pill called upadacitinib can help people with a painful skin condition called hidradenitis suppurativa (HS) who haven't responded to usual treatments. The study will involve adults and teenagers and will check for safety and effectiveness over time. Participants will be randomly given either the medication or a non-active pill, and their progress will be monitored through periodic medical check-ups.

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.

How is the drug Upadacitinib unique for treating hidradenitis suppurativa?

Upadacitinib is unique because it is a selective Janus kinase (JAK)1 inhibitor, which targets specific pathways involved in inflammation, offering a novel approach for treating hidradenitis suppurativa, especially in cases resistant to conventional therapies. ^{1 2 3 4 5}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Upadacitinib (Janus Kinase (JAK) Inhibitor)

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.

Participant Groups

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 Canada for the following indications:

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

Findings from Research

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]

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]

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]

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 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]

References

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

Off-Label Use of Janus Kinase Inhibitors in Inflammatory Cutaneous Diseases. [2023]

2. Sweden pubmed.ncbi.nlm.nih.gov

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

3. England 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. [2021]

4. Slovenia pubmed.ncbi.nlm.nih.gov

Hidradenitis suppurativa in Crohn's disease during adalimumab therapy: a paradox? [2019]

5. 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]