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

JRCT ID: jRCT2061230029

Registered date:27/06/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Hidradenitis Suppurativa
• Date of first enrollment: 07/09/2023
• Target sample size: 1328
• Countries of recruitment: Argentina,Japan,Australia,Japan,Austria,Japan,Belgium,Japan,Brazil,Japan,Bulagaria,Japan,Canada,Japan,Chile,Japan,Colombia,Japan,Croatia,Japan,Czechia,Japan,Egypt,Japan,Finland,Japan,France,Japan,Germany,Japan,Greece,Japan,Hungary,Japan,Ireland,Japan,Israel,Japan,Italy,Japan,Lithuania,Japan,Mexico,Japan,Netherlands,Japan,New Zealand,Japan,Portugal,Japan,Puerto Rico,Japan,Saudi Arabia,Japan,Singapore,Japan,Slovakia,Japan,South Korea,Japan
• Study type: Interventional

Intervention(s)

Oral tablet.

Experimental: Period 1: Upadacitinib Dose A
Participants will receive Upadicitinib Dose A once daily for 16 weeks.

Placebo Comparator: Period 1: Placebo
Participants will receive Placebo once daily for 16weeks.

Experimental: Period 2: Group 1 - Upadacitinib Dose A 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.

Placebo Comparator: Period 2: Group 2 - Placebo 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.

Experimental: Period 2: Group 3 - Upadacitinib Dose A 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.

Experimental: Period 2: Group 4 - Upadacitinib Dose A 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.

Experimental: Period 2: Group 5 - Upadacitinib Dose B 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.

Experimental: Period 2: Group 6 - Placebo
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.

Experimental: Period 3: Long-Term Extension Eligible participants will continue to receive upadacitinib or placebo for 68 weeks. Participants will be followed-up for approximately 30 days.

Outcome(s)

Primary Outcome

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.
[Time Frame: Baseline to Week 16]

Secondary Outcome

-Percentage of Participants Achieving Hidradenitis Suppurative Clinical Response (HiSCR) 75.
HiSCR 75 is defined as at least a 75 percent 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.
[Time Frame: Baseline to Week 16]

-Percentage of Participants Achieving Numeric Rating Scale 30 (NRS30) at Week 4 Among Subjects with NRS or higher 3 at Baseline.
Achievement will be considered at least a 30 percent 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).
[Time Frame: Baseline to Week 4]

-Incidence of Hidradenitis Suppurativa (HS) Flare During Period 1.
Defined as at least one occurrence of a or higher 25percent increase in AN count, with a minimum absolute increase of 2 relative to Baseline.
[Time Frame: 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.
[Time Frame: 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.
[Time Frame: 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 equal not at all/not relevant; 1 equal a little; 2 equal a lot; and 3 equal very much.
[Time Frame: 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.
[Time Frame: Baseline to Week 16]

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Minimum Age:12 Years
-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 or higher 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 or higher 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 or lower 20 at Baseline.

Exclude 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.

Related Information

• Primary Sponsor: Yamazaki Hayato
• Secondary ID(s): NCT05889182