What is the efficacy, safety, and immunogenicity effect of intravenous AVT16 compared to Entyvio® in male and female subjects aged 18 to 80 years with moderate to severe active ulcerative colitis?

Study sites: The National Hospital of Sri Lanka, Colombo North Teaching Hospital, National Hospital, Galle, Jaffna Teaching Hospital, Colombo South Teaching Hospital, Kandy Teaching Hospital,

Randomisation: Eligible subjects will be randomized in a 1:1 ratio into treatment arms. Interactive response technology will be used to administer the randomization schedule. An independent Biostatistician who is not part of the study will generate the randomization schedule using SAS® software Version 9.4 or later (SAS Institute Inc., Cary, North Carolina) for interactive response technology (IRT), which will link sequential subject randomization numbers to treatment codes. The randomization schedule will be stratified by the following: • prior use of glucocorticoids (yes/no) • prior use of immunosuppressive agents (yes/no) and • inadequate response or intolerance to immunomodulators (yes/no)

These details will be entered into the Interactive Response Technology used to randomize the participants. This information will be integrated in the Electronic Data Capture (EDC) system from the IRT system.

Intervention: AVT16 is a proposed biosimilar to Entyvio (vedolizumab). The proposed indication (ulcerative colitis [UC]) and route of administration (intravenous [IV]) for AVT16 are the same as those currently approved for the reference product Entyvio. The study consists of a screening period, an active period, and an end-of-study (EoS) visit. On Day 0 after successfully completing screening activities, subjects will be randomized to receive either AVT16 or Entyvio IV in a 1:1 ratio of patients. Test product: AVT16 300 mg IV Reference product: Entyvio 300 mg IV Both the test and reference drug will be administered as an initial dose of 300 mg IV at Week 0 and Week 2 during the induction phase, then 300 mg IV at Week 6 and every 8 weeks thereafter until Week 46 (Weeks 14, 22, 30, 38, 46) during the maintenance phase. The study duration will be up to 56 weeks including a 4-week screening period. The end of study visit will be at Week 52.

1 Males and females 2 Aged 18 to 80 years (Minimum 18 years and Maximum 80 years). 3 Female participants not pregnant or breastfeeding and using effective contraception if of childbearing potential. 4 Male participants using effective contraception or abstaining if they have female partners of childbearing potential. 5 Diagnosis of ulcerative colitis (UC) established at least 3 months prior to baseline endoscopy, confirmed by clinical, endoscopic, and histopathological evidence. 6 Moderate to severe UC with a Mayo Score of 6 to 12 with an endoscopic subscore greater than or equal to 2 within 14 days prior to the first dose of IP. 7 Evidence of UC extending beyond the rectum (greater than or equal to 15 cm from the anal verge) confirmed by endoscopy at least 3 months prior the baseline endoscopy 8 Documented surveillance colonoscopy for those with long-standing colitis for those of >8 years duration or left-sided colitis of >12 years or colorectal cancer risk factors. 9 History of inadequate response, loss of response, or intolerance to corticosteroids or immunomodulators.

1. Evidence of severe UC complications (e.g., toxic megacolon), significant bowel surgery, or ileostomy/colostomy.
2. Prior treatment with TNF antagonists or other biological therapies for UC.
3. Recent use of certain nonbiologic therapies or topical treatments within specified timeframes.
4. Recent infections, need for surgery, or history of colonic polyps or mucosal dysplasia.
5. Chronic hepatitis B/C, active or latent TB, or immunodeficiency.
6. Recent live vaccination (except influenza), significant extra-intestinal infection, or neurological disorders.
7. Recent surgery or planned major surgery, history of malignancy (with specific exceptions).
8. Clinically significant lab abnormalities, recent alcohol/drug dependence, or active psychiatric issues.
9. Employment or close familial ties to study personnel or inability to comply with study procedures.
10. Evidence of or treatment for Clostridium difficile infection within 60 days or other intestinal pathogen (eg, Salmonella, Escherichia coli, etc.) within 30 days prior to baseline endoscopy.