Phase 3 Randomized, Double-Blind, Placebo-Controlled Study of Upadacitinib in Moderate to Severe Hidradenitis Suppurativa Post Anti-TNF Therapy Failure

The primary objective of this Phase 3 randomized, placebo-controlled, double-blind study is to evaluate the **efficacy** and **safety** of **upadacitinib** in adult and adolescent subjects with moderate to severe **Hidradenitis Suppurativa** (HS) who have failed to respond to or are intolerant of anti-tumor necrosis factor (TNF) therapy. This objective is clinically relevant as it addresses the need for effective treatment options for patients with HS who do not benefit from existing anti-TNF therapies, potentially improving patient outcomes and quality of life.

The clinical trial involves a total of **786 participants** diagnosed with **Hidradenitis Suppurativa** (HS), a chronic skin condition. The study population includes both male and female subjects, aged 12 years and older, with a body weight of at least 30 kg for those between 12 and 18 years of age. Participants have a documented history of moderate to severe HS, characterized by lesions in at least two distinct anatomic areas and a total abscess and nodule count of five or more at baseline. The trial specifically targets individuals who have previously failed to respond to or are intolerant of anti-tumor necrosis factor (TNF) therapy. The selection process ensures that participants are capable of understanding and adhering to the protocol requirements, with informed consent obtained from each subject or their legally authorized representative. The trial includes a vulnerable population, indicating additional ethical considerations in the study design. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, randomized, placebo-controlled, double-blind study designed to evaluate the efficacy and safety of **upadacitinib** in adult and adolescent subjects with moderate to severe **hidradenitis suppurativa** who have failed anti-TNF therapy. The trial aims to assess the primary endpoint of achieving HiSCR 50 at Week 16, which is defined as at least a 50% reduction in the total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline. Secondary endpoints include achieving HiSCR 75, NRS30, and changes from baseline in various assessments such as the Hidradenitis Suppurativa Symptom Assessment and Dermatology Life Quality Index at Week 16.

The trial is expected to commence recruitment on October 23, 2023, and is estimated to conclude by August 1, 2027. Participants will be involved in the study for a maximum treatment period of up to 104 weeks. The study involves several key visits, starting with an inclusion (screening) visit to determine eligibility based on criteria such as age, body weight, and a documented history of previous use of TNF inhibitors or non-anti-TNF biologic therapy. Follow-up visits will be conducted to monitor the participants' response to the treatment and to assess the primary and secondary endpoints. The end-of-study visit will mark the conclusion of the participant's involvement in the trial.

Participants may be withdrawn from the study early if they experience significant adverse effects, fail to adhere to the study protocol, or if the investigator deems it necessary for the participant's safety. The trial will utilize a modified-release tablet form of upadacitinib, administered orally, with a matching placebo for control purposes. The study is not classified as a low-intervention trial, and it is not an orphan drug study. The trial is conducted under the sponsorship of AbbVie Deutschland GmbH & Co. KG, with the primary objective of providing a comprehensive evaluation of upadacitinib's therapeutic potential in the specified patient population.

The clinical trial involves the administration of **Upadacitinib**, a **modified-release tablet** formulated for oral administration. Upadacitinib is a chemical substance developed by AbbVie Deutschland GmbH & Co. KG, identified by the sponsor product code ABT-494. The trial includes two variations of Upadacitinib, each with a distinct maximum treatment period: one for 88 days and another for 104 days. The dosage is expressed in milligrams, although specific daily and total dose amounts are not provided. The primary objective is to evaluate the efficacy and safety of Upadacitinib in adult and adolescent subjects with moderate to severe **Hidradenitis Suppurativa** who have not responded to or are intolerant of anti-TNF therapy.

The study also includes a **matching placebo** for Upadacitinib, which serves as a comparator treatment. The placebo is designed to mimic the pharmaceutical form of Upadacitinib, ensuring the double-blind nature of the trial. The placebo is administered orally, similar to the active medication, although specific details regarding its pharmaceutical form and active substance are not available. The inclusion of a placebo group allows for a controlled assessment of Upadacitinib's therapeutic effects compared to no active treatment.

The efficacy of **Upadacitinib** in the treatment of moderate to severe Hidradenitis Suppurativa (HS) will be assessed through a series of predefined endpoints in a Phase 3 randomized, placebo-controlled, double-blind clinical trial. The primary endpoint is the achievement of HiSCR 50 at Week 16, which 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.

Secondary endpoints include the achievement of HiSCR 75, which requires at least a 75% reduction in the total AN count with no increase in abscess count and no increase in draining fistula count relative to Baseline, also measured at Week 16. Additionally, the trial will assess the achievement of NRS30 at Week 4, which involves at least a 30% reduction and at least 2 units reduction from Baseline in the Patient's Global Assessment of HS-related skin pain NRS among subjects with NRS ≥ 3 at Baseline. Other secondary endpoints include the occurrence of HS flare during Period 1, changes from Baseline in Hidradenitis Suppurativa Symptom Assessment (HSSA), Hidradenitis Suppurativa Impact Assessment (HSIA), Dermatology Life Quality Index (DLQI) for adult subjects and adolescent subjects aged ≥ 16 years, and changes in HS-related odor based on HSSA Question 8, all evaluated at Week 16.