A Study to Assess Change in Disease Activity and Adverse Events of Oral Upadacitinib in Adult and Adolescent Participants With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy (Step-Up HS)

AbbVie

Status and phase: Enrolling; Phase 3

Conditions: Hidradenitis Suppurativa

Treatments: Drug: Upadacitinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT05889182

M23-698

2023-503661-28-00 (Other Identifier)

Details and patient eligibility

About

Hidradenitis suppurativa (HS) is an inflammatory skin disease that causes painful lesions in the axilla (underarm), inguinal (groin) and anogenital (anal/genital) regions. 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 respond to or are intolerant of anti-tumor necrosis factor (TNF) therapy. Adverse events and change in disease activity will be assessed.

Upadacitinib is an approved drug for ulcerative colitis, atopic dermatitis, rheumatoid arthritis, psoriatic arthritis, and axial spondylarthritis and is being developed for the treatment of HS. This study is "double-blinded", meaning that neither the trial participants nor the study doctors will know who will be given upadacitinib and who will be given placebo. This study is comprised of 3 periods. In Period 1, participants are randomized into 2 groups called treatment arms where each group receives a different treatment. There is a 1 in 2 chance that participants will be assigned to placebo. In Period 2, participants are placed into 6 different groups depending on their placement and results in Period 1. Period 3 is the long-term extension period where participants will continue treatment from Period 2. Approximately 1328 adult and adolescent participants diagnosed with HS will be enrolled in approximately 275 sites worldwide.

Participants will receive oral tablets of upadacitinib or placebo once daily for 36 weeks in Period 1 and Period 2. Eligible participants from Period 1 and Period 2 will enter Period 3 and receive oral tablets of upadacitinib or placebo once daily for 68 weeks. Participants will be followed up for approximately 30 days.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular outpatient visits during the study. The effect of the treatment will be checked by medical assessments, checking for side effects and completing questionnaires.

Enrollment: 1,328 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of HS for at least 6 months prior to Baseline, as determined by the investigator (i.e., through medical history and interview of subject).
• Documented history of previous use of ≥ 1 TNF inhibitor for HS for at least 12 weeks and/or 1 approved non-anti-TNF biologic therapy for HS for at least 16 weeks characterized by inadequate response or for any duration characterized by intolerance as determined by the investigator.
• Participant must have a total AN count of ≥ 5 at Baseline.
• HS lesions must be present in at least 2 distinct anatomic areas at Baseline.
• At least 1 anatomic area of HS involvement characterized as Hurley Stage II or higher at Baseline.
• Draining fistula count of ≤ 20 at Baseline.

Exclusion criteria

• History of active skin disease other than HS that could interfere with the assessment of HS, including skin infections (bacterial, fungal, or viral) requiring systemic treatment within 4 weeks of the Baseline visit.
• Treatment with any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug or be currently enrolled in another interventional clinical study. Investigational drugs are also prohibited during the study.
• Previous treatment with any cell-depleting therapies including but not limited to anti-CD20 (e.g., rituximab) within 12 months prior to Baseline or until B cell count returns to normal level or pre-treatment level.
• Use of prescription topical therapies (including topical antibiotics) that can also be used to treat HS within 14 days prior to the Baseline visit.
• Received any systemic (including oral) antibiotic treatment for HS or any other chronic inflammatory disorder within 14 days prior to the Baseline visit.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,328 participants in 9 patient groups, including a placebo group

Period 1: Upadacitinib Dose A

Experimental group

Description:

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

Treatment:

Drug: Upadacitinib

Period 1: Placebo

Placebo Comparator group

Description:

Participants will receive Placebo once daily for 16 weeks.

Treatment:

Drug: Placebo

Period 2: Group 1 - Upadacitinib Dose A

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Period 2: Group 2 - Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Period 2: Group 3 - Upadacitinib Dose A

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Period 2: Group 4 - Upadacitinib Dose A

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Period 2: Group 5 - Upadacitinib Dose B

Experimental group

Description:

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.

Treatment:

Drug: Upadacitinib

Period 2: Group 6 - Placebo

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Period 3: Long-Term Extension

Experimental group

Description:

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

Treatment:

Drug: Placebo

Drug: Upadacitinib