Phase IIa Study Evaluating AZD7798 in Crohn's Disease

Exclusion Criteria

• •1. Evidence, or clinical suspicion, of other forms of IBD or concomitant additional active gastrointestinal luminal inflammatory diseases.
• •2. Known symptomatic strictures or bowel stenoses or strictures preventing passage of endoscope throughout the colon.
• •3. Any complications of Crohn's disease where surgery is anticipated or planned prior to end of study treatment.
• •4. Evidence of extensive prior gastrointestinal surgical interventions.
• •5. Within 3 months prior to screening endoscopy visit:
• •1. History of toxic megacolon
• •2. Diagnosis of peritonitis or need for treatment of peritonitis
• •3. Bowel perforation or evidence of obstruction.
• •6. All intrabdominal abscesses are excluded. Cutaneous and perianal/perirectal abscesses and fistulae are excluded unless adequately drained at least 4 weeks prior to screening endoscopy visit with no anticipation for surgery prior to end of study treatment.
• •7. Ongoing or expected nutritional dependency on total enteral or parenteral nutrition during study.
• •8. Evidence of an increased risk of colorectal cancer.
• •9. Symptomatic oral Crohn's disease within one year.
• •10. Any of the following treatments within the specified time period prior to screening endoscopy visit
• •1. An anti-TNF biologic within 8 weeks prior to screening endoscopy visit
• •2. Any biologic targeting immune response other than an anti-TNF within 12 weeks prior to screening endoscopy visit
• •3. Other advanced small molecule treatments for Crohn's disease within 4 weeks prior to screening endoscopy visit
• •4. Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus (FK-506) within 4 weeks prior to screening endoscopy visit
• •5. Treatment with apheresis within 4 weeks prior to screening endoscopy visit
• •6. Administration of any live vaccine within 4 weeks prior to screening endoscopy visit to end of study
• •7. Faecal microbiota transplantation within 4 weeks prior to screening endoscopy visit
• •8. Lymphocyte-depleting treatment within 12 months prior to screening endoscopy visit
• •9. Any previous exposure to AZD7798.
• •11. Any changes in dosing of the following medications prior to screening endoscopy visit as outlined:
• •1. 5-aminosalicylates within 2 weeks
• •2. Oral corticosteroids within 2 weeks or stable doses of steroids exceeding the following dose equivalents:
• •(i) Systemic steroids \> 20 mg/day or prednisolone equivalent (ii) Locally targeted steroids exceeding maximum budesonide dose equivalent (9 mg/day) (c) Immunomodulators within 4 weeks (d) Antibiotic therapy for the treatment of Crohn's disease (e) Probiotics within 2 weeks.
• •12. Known or suspected history of chronic use of nonsteroidal anti-inflammatory drugs.
• •13. Evidence of recent or currently active infection, including use of IV or oral antibiotics for documented infection within 30 days prior to screening endoscopy visit.
• •14. Evidence of chronic HBV or HCV.
• •15. History of TB (active or latent) unless an appropriate course of treatment has been completed.
• •16. Positive diagnostic TB test at screening.
• •17. History of serious opportunistic infection within 12 months prior to screening endoscopy visit.
• •18. CMV colitis within previous 12 months prior to screening endoscopy visit.
• •19. Positive C. difficile toxin stool test at screening.
• •20. Symptomatic herpes zoster infection within 3 months prior to screening endoscopy.
• •21. Any identified immunodeficiency.
• •22. Abnormal laboratory results at screening suggesting participation may be unsafe, which will prevent the patient from completing the study, or will interfere with the interpretation of the study results.
• •23. Reproduction:
• •1. Pregnant and breastfeeding patients, or those planning to breastfeed during the study
• •2. FOCBP unless completely abstinent or using a highly effective contraception and barrier method of contraception.
• •24. Prolonged QTcF interval.
• •25. Clinically significant cardiovascular conditions.
• •26. Current malignancy or history of malignancy.
• •27. Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, haematological disease, hepatic disease, renal disease, gastrointestinal disease or other major disease other than active Crohn's disease.
• •28. Current enrolment in another interventional study or treatment with any investigational drug within 4 months prior to screening endoscopy visit.
• •29. Unstable lifestyle factors.
• •30. Patients committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
• •31. Investigator concerns regarding patient's willingness and ability to attend all study visits, comply with the study procedures, read in order to complete questionnaires, or to complete the study period