Phase IIa Study Evaluating AZD7798 in Crohn's Disease

Eligibility Criteria

• 1. 18 to 80 years of age.
• 2. Diagnosis of Crohn's disease established with verifiable clinical, imaging, endoscopic and/or histopathologic evidence.
• 3. Moderate to severe active Crohn's disease.
• 4. Ileal/ileocecal (L1), colonic (L2), or ileocolonic (L3) disease, as classified based on the localisation of active inflammation.
• 5. Capable of giving signed informed consent.
• 6. A history of at least one of:
• 1. Intolerance or inadequate response to conventional treatment (oral corticosteroid, azathioprine, 6-mercaptopurine, or methotrexate), biologics, or other approved advanced therapy (eg, JAK inhibitors) OR
• 2. Corticosteroid dependency (defined as inability to taper below budesonide 6 mg/day or prednisolone 10 mg/day without recurrent active disease) for the treatment of Crohn's disease.
• 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. Undrained fistula or abscess, including intrabdominal abscesses.
• 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:
• 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.