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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Randomized, Placebo-Controlled, Double-Blind Study to Evaluate Efficacy and Safety of Upadacitinib in Adult and Adolescent Subjects With Moderate to Severe Hidradenitis Suppurativa Who Have Failed Anti-TNF Therapy

Conditions
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Hidradenitis Suppurativa

Intervention / Treatment
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* Drug: Upadacitinib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: Upadacitinib Dose A<br>Participants will receive Upadicitinib Dose A once daily for 16 weeks. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Placebo Comparator: Period 1: Placebo<br>Participants will receive Placebo once daily for 16 weeks. | Drug: Placebo<br>* Oral Tablets<br>|
| Experimental: Period 2: Group 1 - Upadacitinib Dose A<br>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. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Placebo Comparator: Period 2: Group 2 - Placebo<br>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. | Drug: Placebo<br>* Oral Tablets<br>|
| Experimental: Period 2: Group 3 - Upadacitinib Dose A<br>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. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2: Group 4 - Upadacitinib Dose A<br>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. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2: Group 5 - Upadacitinib Dose B<br>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. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;|
| Experimental: Period 2: Group 6 - Placebo<br>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. | Drug: Placebo<br>* Oral Tablets<br>|
| Experimental: Period 3: Long-Term Extension<br>Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days. | Drug: Upadacitinib<br>* Oral Tablets<br>* Other names: RINVOQ;Drug: Placebo<br>* Oral Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 50 | HiSCR 50 is defined as at least a 50% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline. | Baseline to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 75 | HiSCR 75 is defined as at least a 75% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess count and no increase in draining fistula count relative to Baseline. | Baseline to Week 16 | 
| Percentage of Participants Achieving Numeric Rating Scale 30 (NRS30) at Week 4 Among Subjects with NRS ≥ 3 at Baseline | Achievement will be considered at least a 30% reduction and at least 2 units reduction from Baseline in NRS scale in the Patient's Global Assessment (PGA) of HS-related skin pain based on worst skin pain in a 24-hour recall period (maximal daily pain). The PGA Skin Pain is an 11-point numerical rating scale with ratings for the item ranging from 0 (no skin pain) to 10 (skin pain as bad as you can imagine). | Baseline to Week 4 | 
| Incidence of Hidradenitis Suppurativa (HS) Flare During Period 1 | Defined as at least one occurrence of a ≥ 25% increase in AN count, with a minimum absolute increase of 2 relative to Baseline. | Week 16 | 
| Change from Baseline in Hidradenitis Suppurativa Symptom Assessment (HSSA) | The HSSA (24-hour recall) is a 9-item PRO questionnaire developed to assess the primary symptoms of HS in the 7 consecutive days prior to assessments. Each item of the HSSA is scored on an 11-point (0 to 10) NRS, where 0 represents no symptoms and 10 represents extreme symptom experience. | Baseline to Week 16 | 
| Change from Baseline in Hidradenitis Suppurativa Impact Assessment (HSIA) | The HSIA is an 18-item PRO questionnaire developed to assess the impact of HS on the daily lives of subjects in the 7 days prior to the assessment. Items 1 - 16 of the HSIA are scored on a 0 to 10 NRS, where 0 represents no impact and 10 represents extreme impact. | Baseline to Week 16 | 
| Change from Baseline in Dermatology Life Quality Index (DLQI) for Adult Subjects and Adolescent Subjects Age 17 Years Old or Children's DLQI (CDLQI) for Adolescent Subjects Ages 12 to 16 Years Old | The DLQI and the CDLQI are both 10-item questionnaires used to assess the impact of hidradenitis suppurativa (HS) disease symptoms and treatment on quality of life that consists of 10 questions scored on a 4-point scale where 0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much. | Baseline to Week 16 | 
| Change from Baseline in Hidradenitis Suppurativa (HS)-Related Odor, Based on Hidradenitis Suppurativa Symptom Assessment (HSSA) Question 8 | The HSSA (24-hour recall) is a 9-item PRO questionnaire developed to assess the primary symptoms of HS in the 7 consecutive days prior to assessments. Each item of the HSSA is scored on an 11-point (0 to 10) NRS, where 0 represents no symptoms and 10 represents extreme symptom experience. | Baseline to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hidradenitis Suppurativa, Upadacitinib, ABT-494, Rinvoq, STEP-UP HS