Long-Term Efficacy, Safety, and Tolerability of Repeated Upadacitinib Administration in Crohn's Disease: A Phase 2 Multicenter Open-Label Extension Study

The primary objective of this study is to observe the long-term **efficacy**, safety, and tolerability of repeated administration of **upadacitinib** in subjects with **Crohn's Disease** who have completed Study M13-740. This objective is clinically relevant as it aims to provide insights into the sustained therapeutic benefits and potential risks associated with prolonged use of upadacitinib, a treatment option for managing Crohn's Disease. Understanding these aspects is crucial for optimizing long-term treatment strategies and improving patient outcomes in this chronic inflammatory condition.

The clinical trial involves a total of **21 participants** diagnosed with **Crohn's Disease (CD)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their completion of Study M13-740 through Week 52, ensuring a consistent baseline for observing the long-term efficacy, safety, and tolerability of repeated administration of upadacitinib. The trial includes a vulnerable population, indicating that special considerations are in place to protect these individuals. Female participants are required to be postmenopausal, surgically sterile, or using a birth control method. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the study population is well-defined and appropriate for the objectives of the trial.

The clinical trial is designed to evaluate the long-term efficacy, safety, and tolerability of repeated administration of **upadacitinib** in subjects with **Crohn's disease** who have completed a prior study, M13-740. This is a Phase 2, multicenter, open-label extension study. The trial will involve the administration of upadacitinib in the form of modified-release tablets, with a maximum daily dose of 30 mg and a total treatment period of up to 96 months. The study is not categorized as low intervention and is intended to provide comprehensive data on the long-term effects of the treatment.

Participants will be required to have completed the previous study through Week 52 to be eligible for inclusion. The primary endpoints include the proportion of subjects achieving remission and maintaining it over various time points, as well as achieving clinical and endoscopic responses. Secondary endpoints focus on changes in clinical parameters such as stool frequency, abdominal pain, and inflammatory markers from the baseline of the previous study.

The trial will commence with a screening visit to confirm eligibility, followed by regular follow-up visits at specified intervals, including Months 12, 24, 36, 48, 60, 72, 84, and 96. These visits are designed to monitor the participants' response to the treatment and assess any adverse effects. The end-of-study visit will conclude the trial, providing a final assessment of the long-term outcomes of the treatment.

Participant involvement is expected to last up to 96 months, depending on individual response and adherence to the study protocol. Conditions that may lead to early termination from the study include significant adverse events, non-compliance with the study protocol, or withdrawal of consent by the participant. The trial is estimated to end by October 2025, with recruitment having started in October 2016.

The clinical trial involves the administration of **Upadacitinib**, a **modified-release tablet** developed by AbbVie Deutschland GmbH & Co. KG. The active substance, upadacitinib, is of chemical origin and is utilized in two different dosages for the study. The first dosage involves a maximum daily dose of 30 mg, with a total maximum dose of 86400 mg over a treatment period of 96 weeks. The second dosage involves a maximum daily dose of 15 mg, with a total maximum dose of 43200 mg over the same treatment period. Both dosages are administered orally. The pharmaceutical form is consistent across both dosages, ensuring a controlled release of the active substance.

In this open-label extension study, the primary objective is to observe the long-term efficacy, safety, and tolerability of repeated administration of upadacitinib in subjects with **Crohn's disease**. The study does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. Participant compliance is monitored through regular assessments to ensure adherence to the dosing schedule. The trial is designed to provide comprehensive data on the long-term effects of upadacitinib in the specified patient population.

The efficacy of the clinical trial involving **Upadacitinib** for Crohn's Disease will be assessed through a series of primary and secondary endpoints. The primary endpoints include the proportion of subjects achieving remission at various timepoints, specifically at Week 0 (Week 52 of Study M13-740), and at Months 12, 24, 36, 48, 60, 72, 84, and 96. Additionally, the trial will evaluate the proportion of subjects maintaining remission, achieving clinical and endoscopic remission, and response over time. Other primary endpoints involve the assessment of Crohn's Disease Activity Index (CDAI) remission and response, as well as the Inflammatory Bowel Disease Questionnaire (IBDQ) remission and response.

Secondary endpoints will focus on the time to dose escalation, changes from baseline in stool frequency, abdominal pain, CDAI, high-sensitivity C-reactive protein (hs-CRP), and fecal calprotectin at every visit. The trial will also measure changes in the Simple Endoscopic Score for Crohn's Disease at specified intervals, the proportion of subjects achieving remission with normal hs-CRP and fecal calprotectin levels, and the discontinuation of corticosteroid use. Additional secondary endpoints include changes in IBDQ, EuroQol Dimensions 5 Levels, and Work Productivity and Impairment Questionnaire (WPAI) over time, as well as the proportion of subjects with CD-related hospitalizations, surgeries, and procedures, and changes in extraintestinal manifestations.