Phase IIa Study Evaluating AZD7798 in Crohn's Disease

Prior treatment

• Evidence, or clinical suspicion, of other forms of IBD or concomitant additional active gastrointestinal luminal inflammatory diseases.
• Any complications of Crohn's disease where surgery is anticipated or planned prior to end of study treatment.
• Evidence of extensive prior gastrointestinal surgical interventions.
• Within 3 months prior to screening endoscopy visit:
  • History of toxic megacolon
  • Diagnosis of peritonitis or need for treatment of peritonitis
  • Bowel perforation or evidence of obstruction.
• 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.
• Any initiation or changes in dosing of the following medications prior to screening endoscopy visit as outlined: (a) 5-aminosalicylates within 2 weeks (b) 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) Steroids with limited systemic effects (eg, budesonide and beclomethasone), 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.
• Chronic use of nonsteroidal anti-inflammatory drugs.
• 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.
• History of serious opportunistic infection within 12 months prior to screening endoscopy visit.
• CMV colitis within previous 12 months prior to screening endoscopy visit.
• Symptomatic herpes zoster infection within 3 months prior to screening endoscopy.
• Current enrolment in another interventional study or treatment with any investigational drug within 4 months prior to screening endoscopy visit.

Other illness

• Evidence of an increased risk of colorectal cancer.
• Symptomatic oral Crohn's disease within one year.
• Evidence of chronic HBV or HCV.
• History of TB (active or latent) unless an appropriate course of treatment has been completed.
• Clinically significant cardiovascular conditions.
• Current malignancy or history of malignancy.
• 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.

Lab values

• Any of the following treatments within the specified time period prior to screening endoscopy visit
  • An anti-TNF biologic within 8 weeks prior to screening endoscopy visit
  • Any biologic targeting immune response other than an anti-TNF within 12 weeks prior to screening endoscopy visit
  • Other advanced small molecule treatments for Crohn's disease within 4 weeks prior to screening endoscopy visit
  • Cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, or tacrolimus (FK-506) within 4 weeks prior to screening endoscopy visit
  • Treatment with apheresis within 4 weeks prior to screening endoscopy visit
  • Administration of any live vaccine within 4 weeks prior to screening endoscopy visit to end of study
  • Faecal microbiota transplantation within 4 weeks prior to screening endoscopy visit
  • Lymphocyte-depleting treatment within 12 months prior to screening endoscopy visit
  • Any previous exposure to AZD7798.
• 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.

Other

• Symptomatic strictures or bowel stenoses, or strictures preventing passage of endoscope throughout the colon (including at screening endoscopy).
• Ongoing or expected nutritional dependency on total enteral or parenteral nutrition during study.
• Positive diagnostic TB test at screening.
• Positive C. difficile toxin stool test at screening.
• Any identified immunodeficiency.
• Reproduction:
  • Pregnant and breastfeeding patients, or those planning to breastfeed during the study
  • FOCBP unless completely abstinent or using a highly effective contraception and barrier method of contraception.
• Prolonged QTcF interval.
• Unstable lifestyle factors.
• Patients committed to an institution by virtue of an order issued either by the judicial or the administrative authorities.
• 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

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