Eine offene, vom Prüfarzt initiierte Studie zur Bewertung der Anwendung von Upadacitinib bei Patienten mit akuter schwerer Colitis ulcerosa im Krankenhaus

Inclusion Criteria:

• Male or female ≥18 and ≤75 years of age hospitalized with ASUC (Mayo score >10 or Truelove and Witts criteria)
• Diagnosis of UC for at least 90 days, confirmed by colonoscopy; appropriate documentation of biopsy results consistent with the diagnosis of UC
• No prior use of upadacitinib
• Capable of providing informed consent
• For women of childbearing potential: negative pregnancy test at screening and agreement to use acceptable contraception throughout study participation

Exclusion Criteria:

• • Current diagnosis of Crohn's disease, indeterminate colitis, fulminant colitis, and/or toxic megacolon

  • Disease limited to the rectum during screening endoscopy
  • History of colectomy with ileoanal pouch, Kock pouch, or ileostomy for UC or was planning bowel surgery
  • Infections requiring treatment with IV anti-infectives within 30 days before baseline or oral anti-infectives within 14 days before baseline
  • Contraindication to IL-23 agent if advanced therapy-naïve
  • Known hypersensitivity to upadacitinib or any excipients
  • History of lymphoproliferative disorder, lymphoma, leukemia, or any malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or cervical carcinoma in situ
  • History of venous thromboembolic event (DVT, PE) within past 12 months
  • Any condition that, in the investigator's opinion, would compromise the participant's safety or study outcomes
  • History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months prior to Baseline.
  • Meeting any of the following conditions at Baseline:
  • Two or more prior episodes of herpes zoster, or one or more episodes of disseminated herpes zoster;
  • One or more prior episodes of disseminated herpes simplex (including eczema herpeticum);
  • Human immunodeficiency virus (HIV) infection, defined as confirmed positive anti-HIV antibody (HIV Ab) test or a positive HIV Ab/Ag test
  • Active TB or meet TB exclusionary parameters (specific requirements for TB testing are provided in the operations manual);
  • Active infection(s) requiring treatment with intravenous anti-infectives within 30 days, or oral/intramuscular anti-infectives within 14 days prior to the Baseline Visit;
  • Chronic recurring infection and/or active viral infection that, based on the investigator's clinical assessment, makes the subject an unsuitable candidate for the study;
  • COVID-19 infection: In subjects who tested positive for COVID-19, at least 5 days must have passed between a COVID-19 positive test result and the Baseline visit of asymptomatic subjects. Subjects with mild/moderate COVID-19 infection can be enrolled if fever is resolved without use of antipyretics for 24 hours and other symptoms improved, or if 5 days have passed since the COVID-19 positive test result (whichever comes last). Subjects may be rescreened if deemed appropriate by the investigator based upon the subject's health status.
  • HBV and HCV screening values that meet the following criteria at the most recent testing prior to the first dose of study drug :
  • HBV: hepatitis B surface antigen (HBs Ag) positive (+) test or detectable HBV deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) qualitative test for subjects who are hepatitis B core antibody (HBc Ab) positive (+)
  • HCV: detectable HCV ribonucleic acid (RNA) in any subject with anti-HCV antibody (HCV Ab).
  • At Baseline any of the following medical diseases or disorders:
  • Recent (within past 6 months) cerebrovascular accident, myocardial infarction, coronary stenting, (note: include the following only for new protocols) aorto-coronary bypass surgery, or venous thromboembolism;
  • History of an organ transplant which requires continued immunosuppression;
  • History of an allergic reaction or significant sensitivity to constituents of the study drug (and its excipients) and/or other products in the same class;
  • History of GI perforation (other than due to appendicitis or mechanical injury), diverticulitis, or significantly increased risk for GI perforation per investigator judgment;
  • Conditions that could interfere with drug absorption including but not limited to short bowel syndrome or gastric bypass surgery; subjects with a history of gastric banding/segmentation are not excluded;
  • History of malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix;
  • Females of child-bearing potential who do not meet the following:
  • Subjects must not have a positive serum pregnancy test at the Screening Visit and must have a negative urine pregnancy test at Baseline prior to the first dose of study drug (local practices may require serum pregnancy testing at Baseline).
  • Subjects with a borderline serum pregnancy test at Screening must have absence of clinical suspicion of pregnancy or other pathological causes of borderline results and a serum pregnancy test ≥ 3 days later to document continued lack of a positive result (unless inclusion of subjects with a borderline pregnancy test may be prohibited by local requirements).
  • Subjects with a urine pregnancy test at Baseline that is borderline or ambiguous must have a serum pregnancy test performed. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
  • Female subjects of childbearing potential who are not able and/or willing to practice at least 1 protocol-specified method of birth control that is highly effective from Study Day 1 through at least 30 days after the last dose of study drug (local practices may require an additional method of contraception) (refer to Section 5.2 for more detail on contraception). Female subjects of non-childbearing potential do not need to use birth control.
  • Female subjects who are pregnant, breastfeeding, or considering becoming pregnant during the study and for 30 days after the last dose of study drug.
  • Subjects who have been treated with any investigational drug of chemical or biologic nature within 30 days or five half-lives (whichever is longer) prior to the first dose of study drug or who are currently enrolled in another interventional clinical study.
  • Subjects with systemic use of known strong cytochrome P450 3A (CYP3A) inhibitors at Screening or strong CYP3A inducers 30 days prior to study drug administration. Herbal therapies and other traditional medicines with unknown effect on CYP3A taken systemically are prohibited within 30 days prior to Baseline. Herbal therapies and other traditional medicines are defined as any herbal formulation that is intended to treat or prevent health problems and may include supplements based on herbs which the subject is taking.
  • Subjects who have received any live vaccine with replicating potential within 30 days (or longer if required locally) prior to the first dose of study drug, or have expected need of vaccination with any live vaccine with replicating potential during study participation including at least 30 days (or longer if required locally) after the last dose of study drug. Live vaccines that are incapable of replicating are permitted.
  • Screening laboratory values that meet the following criteria at the most recent testing prior to the first dose of study drug:
  • Serum aspartate transaminase (AST) > 2 × ULN;
  • Serum alanine transaminase (ALT) > 2 × ULN;
  • Estimated glomerular filtration rate (GFR) by simplified 4-variable MDRD formula < 30 mL/min/1.73 m2;
  • Total white blood cell (WBC) count < 2,500/µL;
  • Absolute neutrophil count (ANC) < 1,200/µL;
  • Platelet count < 100,000/µL;
  • Absolute lymphocyte count < 750/µL;
  • Hemoglobin < 9 g/dL.