AZD7798 Safety, Tolerability, and Pharmacokinetics after a single ascending and repeat dose administrations to healthy subjects, and patients with Crohn's disease

Exclusion Criteria

• All Study Parts:
• • Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of Investigational Medicinal Product (IMP).
• • Any positive result on Screening for HBsAg, anti-HBc antibody, anti-HCV antibody, and HIV.
• • History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or, history of hypersensitivity to drugs with a similar chemical structure or class to AZD7798.
• • For females of childbearing potential using hormonal contraception: Use of drugs with enzyme inducing properties such as St John’s Wort within 3 weeks prior to the first administration of IMP.
• • Subjects with a positive diagnostic nucleic acid test (using PCR) for SARS-CoV-2 prior to dosing.
• • Live or attenuated vaccine within 4 weeks of Visit 1 and until the end of the follow up period.
• • An active infection, or history of serious infection within the preceding 28 days.
• • Use of antibiotics within 28 days prior to the first administration of IMP.
• • History of symptomatic herpes simplex (excluding cold sores) or herpes zoster infection within 3 months prior to screening.
• • Positive or indeterminate TB QuantiFERON test.
• • Has received another new chemical entity within 30 days/5 half-lives of the first administration of IMP in this study.
• • Subjects who cannot communicate reliably with the Investigator.
• • Vulnerable subjects.
• Part 1 (Healthy Subjects), Part 3a (Japanese Subjects, and Part 3b (Chinese Subjects):
• • Any laboratory values with deviations.
• • Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results other than those described under exclusion criterion number 20, as judged by the Investigator.
• • Abnormal vital signs, after 5 minutes supine rest at screening and admission.
• • Known or suspected history of drug abuse in the last 1 year as judged by the Investigator.
• • History of alcohol abuse or excessive intake of alcohol within the last 1 year. as judged by the Investigator.
• • Positive screen for drugs of abuse at screening or admission to the Clinical Unit or positive screen for alcohol on admission to the Clinical Unit prior to the first administration of the IMP.
• • Excessive intake of caffeine containing drinks or food (eg, coffee, tea, chocolate,) as judged by the Investigator.
• Part 1a (in case of dose escalation in patients) and Part 2 (Patients with Crohn’s Disease):
• • Patients with any uncontrolled medical conditions, other than active Crohn’s disease, that in the opinion of the Investigator put the patient at unacceptable risk or interfere with study assessments or integrity of the data.
• • Current diagnosis of ulcerative colitis, indeterminate colitis, inflammatory bowel disease-unclassified, infectious colitis, or ischaemic colitis.
• • History of CMV colitis 12 months prior to screening.
• • Patients with fulminant Crohn’s disease or toxic megacolon.
• • Planned surgery for Crohn’s disease prior to the end of study follow up visit.
• • Patients with symptomatic intestinal stenosis, known pre-stenotic dilatation, undrained fistula(e), or abscesses.
• • Initiation or change in dose of azathioprine or mercaptopurine (including initiation or discontinuation of allopurinol) within 4 weeks of the first administration of IMP.
• • Treatment with methotrexate, ciclosporin, tacrolimus or thalidomide within 4 weeks of the first administration of IMP.
• • Treatment with an anti-TNF biologic within 8 weeks of the first administration of IMP, unless therapeutic drug monitoring is performed and drug concentrations are undetectable.
• • Treatment with any biologic, other than an anti-TNF, within 12 weeks or with undetectable serum concentrations prior to the first administration of IMP, unless therapeutic drug monitoring is performed and drug concentrations are undetectable.
• • Treatment with rituximab within 12 months prior to the first administration of IMP.
• • Any laboratory values with deviations.
• • Any clinically important abnormalities in clinical chemistry, haematology or urinalysis results other than those described under exclusion criterion number 49, as judged by the Investigator.
• • Abnormal vital signs, after 5 minutes supine rest, defined as any of the following at screening and admission.
• • Any clinically important abnormalities in rhythm, conduction, or morphology of the resting ECG and any clinically important abnormalities in the 12 lead ECG.
• • Unstable lifestyle factors, such as alcohol use to excess or recreational drug use, to the extent that in the opinion of the Investigator they would interfere with the ability of a patient to complete the study.
• • Current malignancy or history of malignancy.