Evaluation of Long-Term Safety and Efficacy of Upadacitinib in Patients with Ulcerative Colitis: A Phase 3 Multicenter Extension Study

The primary objective of this Phase 3 multicenter, long-term extension study is to evaluate the **long-term safety** and **efficacy** of **Upadacitinib** (ABT-494) in subjects with **Ulcerative Colitis**. This is clinically relevant as it aims to provide comprehensive data on the sustained use of Upadacitinib, a Janus kinase (Jak) 1 inhibitor, which could potentially offer a new therapeutic option for managing this chronic inflammatory bowel disease. The study does not list any secondary objectives.

The clinical trial involves a total of **550 participants** diagnosed with **Ulcerative Colitis**. The study population includes both male and female subjects, encompassing a wide age range from adolescents to older adults. Participants were selected based on their previous involvement in related studies, specifically those who did not respond to treatment or lost response during maintenance periods, as well as those who completed prior studies. The trial includes individuals who are in stable clinical remission and have not required new or increased medication for Ulcerative Colitis in the six months preceding randomization. Participants are required to be in otherwise good health, as determined by the principal investigator, and must have a fecal calprotectin level of ≤ 250 mg/kg. The study also considers lifestyle factors, such as the absence of corticosteroid treatment for at least 90 days prior to randomization. Both genders are included, and the trial acknowledges the inclusion of a vulnerable population. Participants must be able to provide informed consent and comply with study requirements.

The clinical trial is a **Phase 3** multicenter, long-term extension study designed to evaluate the safety and efficacy of **Upadacitinib** in subjects with **Ulcerative Colitis**. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The study is expected to span approximately ten years, with an estimated recruitment start date of May 12, 2017, and an anticipated end date of June 14, 2027.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific inclusion criteria, such as previous participation in related studies and clinical response status. The trial includes a main study and a dose optimization substudy, each with distinct endpoints and criteria. The primary endpoint focuses on the incidence of adverse events, while secondary endpoints assess the proportion of subjects achieving clinical remission per the Adapted Mayo score at specified intervals.

Study visits will occur at regular intervals, including baseline assessments at Week 0, followed by evaluations at Week 48 and every 48 weeks thereafter. These visits will involve assessments of clinical remission, vital signs, physical examinations, and laboratory tests. The end-of-study visit will mark the conclusion of the participant's involvement, with comprehensive evaluations to assess long-term outcomes.

Participant involvement is expected to last up to 288 weeks, depending on individual response and study progression. Conditions that may lead to early termination from the study include the occurrence of significant adverse events, non-compliance with study protocols, or withdrawal of consent. The trial aims to provide valuable insights into the long-term safety and efficacy of Upadacitinib for the treatment of Ulcerative Colitis, contributing to the advancement of therapeutic options for this condition.

The clinical trial involves the administration of **Upadacitinib**, a **Janus kinase (Jak) 1 inhibitor**, in the form of a **modified-release tablet**. The experimental medication is provided in three different dosages: 7.5 mg, 15 mg, and 30 mg. The tablets are administered orally. The maximum daily dose for the 7.5 mg formulation is 7.5 mg, with a total maximum dose of 15,120 mg over a treatment period of 288 days. For the 15 mg formulation, the maximum daily dose is 15 mg, with a total maximum dose of 30,240 mg over the same period. The 30 mg formulation allows for a maximum daily dose of 30 mg, with a total maximum dose of 60,480 mg. The active substance, **upadacitinib**, is of chemical origin and is manufactured by AbbVie Deutschland GmbH & Co. KG. The medication is not a paediatric formulation and is not classified as an orphan drug.

The study also includes a **placebo** for the upadacitinib tablet, which serves as a non-experimental treatment. The placebo is used to compare the effects of the active medication and does not contain any active substance. The placebo is administered in a manner consistent with the experimental medication to maintain the study's integrity. The placebo's pharmaceutical form and route of administration are not specified, but it is implied to match the experimental treatment for blinding purposes.

The efficacy of **Upadacitinib** in the clinical trial will be assessed through specific endpoints designed to evaluate its impact on subjects with Ulcerative Colitis. The primary efficacy endpoint for the main study is the proportion of subjects achieving clinical remission as defined by the Adapted Mayo Score. This score includes parameters such as Stool Frequency Score (SFS) ≤ 1 and not greater than baseline, Rectal Bleeding Score (RBS) of 0, and an endoscopy subscore ≤ 1. These assessments will occur at Week 0, Week 48, and every 48 weeks thereafter.

In the Dose Optimization Substudy, the efficacy endpoint is similarly defined by the proportion of subjects achieving clinical remission per the Adapted Mayo Score at Week 48. This includes SFS ≤ 1 and not greater than baseline, RBS of 0, an endoscopy subscore ≤ 1 without friability, and the absence of corticosteroid use during the 48-week period. The efficacy assessments will be conducted using validated scales and clinical evaluations to ensure accurate and reliable data collection throughout the trial duration.