Two global Phase 3 trials are evaluating upadacitinib as a potential treatment for adults with moderately to severely active Crohn’s disease (CD) or ulcerative colitis (UC).
The studies will evaluate the safety and efficacy of AbbVie’s therapy. Both are multi-center, double-blind and placebo-controlled. Patient enrollment is ongoing at CB Flock Research Corp. in Mobile, Alabama, for the UC trial (NCT03653026), and at several locations in the CD trial (NCT03345836). Some locations have yet to open.
Upadacitinib (ABT-494) is an investigational oral treatment that belongs to a class of compounds called JAK inhibitors. By blocking the actions of the JAK family of signaling proteins, these molecules reduce pro-inflammatory and autoimmune responses.
The UC trial, named U-Accomplish, will compare upadacitinib to placebo in inducing clinical remission at week eight, as assessed by the Adapted Mayo score. Another outcome measure at week eight will be the proportion of participants with endoscopic improvement or remission, defined as endoscopic subscore lesser than or equal to one or equal to zero, respectively. Other measures at that time will include the proportion of participants with no bowel urgency or abdominal pain; histologic improvement, mucosal healing, UC-related surgeries or hospitalizations, and achieving response in the Inflammatory Bowel Disease Questionnaire (IBDQ) fatigue item or the IBDQ Bowel Symptom domain.
At week 2, the scientists will assess the proportion of participants with clinical response through the Partial Adapted Mayo score.
AbbVie expects to enroll 462 participants ages 18-75 for this trial. It is expected to end in July 2024. Eligible patients must have UC for 90 days or longer, an Adapted Mayo score of five to nine points, and inadequate or no response (or intolerance) to oral aminosalicylates, corticosteroids, immunosuppressants, or biologic therapies, among other criteria.
The CD study will compare upadacitinib to placebo as induction therapy in patients with inadequate response or intolerant to biologic therapy. Two doses of the potential treatment will be tested for 12 weeks. The main outcome measures are the proportion of participants with clinical remission —based on average daily stool frequency and daily abdominal pain score — and with endoscopic response, defined as decreased Simple Endoscopic Score for CD.
Other parameters to be analyzed include fatigue (using the Functional Assessment of Chronic Illness Therapy-Fatigue — Crohn’s Symptoms Severity Questionnaire), the proportion of participants with improved clinical response, those achieving response in the IBDQ Bowel Symptom domain, the proportion of patients with clinical remission per the Crohn’s Disease Activity Index, endoscopic remission, hospitalizations because of CD, over 50% reduction in draining fistulas, and discontinued corticosteroid use with clinical remission.
The company plans to recruit 855 participants ages 18-75. The study is expected to be completed in March 2021. Eligible patients must have moderate to severe CD for at least three months and evidence of mucosal inflammation, among other criteria.
Prior results of the ongoing U-ACHIEVE Phase 2b/3 dose-ranging trial (NCT02819635) revealed that 14-20% of patients treated with upadacitinib (15/30/45 mg, once daily) achieved clinical remission at week eight compared to none on placebo. Upadacitinib was also associated with endoscopic improvement, clinical remission, and clinical response.
No new safety signals were detected. Serious adverse events occurred in up to 6% of upadacitinib-treated patients, compared to 11% with placebo.
Most participants in this trial had failed multiple prior therapies, including biologics. In comparison to placebo, the patients on upadacitinib also reported eased UC symptoms, including bowel urgency, abdominal pain, rectal bleeding and stool frequency, as well as improved disease-specific and general health-related quality of life, less fatigue, and greater work productivity and ability to perform daily activities.
“These results support the initiation of the Phase 3 clinical trial program,” Marek Honczarenko, MD, PhD, AbbVie’s vice president, global immunology development, said in a press release.
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