Efficacy, Safety and Immunogenicity of the Proposed Biosimilar Vedolizumab PB016 in Comparison With Entyvio®

This is a multi-center, randomized, parallel arm, double-blind study with a total duration of 54 weeks. Approximately 750 participants with moderately to severely active Colitis Ulcerosa will be randomized to receive up to eight doses of either PB016 or Entyvio®.

The study will be conducted at up to 200 study centers, located in approximately 18 countries worldwide.

The clinical trial is designed to compare the efficacy, safety, and immunogenicity of 300 mg IV PB016 versus Entyvio® in patients with moderately to severely active UC.

The active period of Study PB016-03-01 comprises the following:

• Stage 1: Induction Period - after 1:1 randomization, intravenous infusions of either PB016 or Entyvio® at a dose of 300 mg at Weeks 0 and 2.
• Stage 2: Maintenance Period - further doses at Weeks 6, 14, 22, 30, 38, and 46.
• Stage 3: Follow-up Period - At Week 54, a safety follow-up call will be conducted.

(Selected) Inclusion Criteria:

• Age ≥18 and ≤75 years at Screening.
• At Screening, females of childbearing potential must be non-pregnant and non-lactating; or females should be of non-childbearing potential (either surgically sterilized or physiologically incapable of becoming pregnant, or at least 1 year post-menopausal [amenorrhea duration of 12 consecutive months]); non-pregnancy will be confirmed for all females of childbearing potential by a serum pregnancy test conducted at Screening.
• Female patients of childbearing potential, with a fertile male sexual partner, must use adequate contraception from Screening until 18 weeks after the last dose of study drug. Adequate contraception is defined as using hormonal contraceptives or an intrauterine device, combined with at least one of the following forms of contraception: a diaphragm or cervical cap, or a condom. Total abstinence from heterosexual activity, in accordance with the lifestyle of the patient, is acceptable.
• Male patients who are sexually active with women of childbearing potential agree they will use adequate contraception from Screening until 90 days after the last dose of study drug if not surgically sterilized at least 6 months before Screening (with a post-vasectomy semen analysis negative for sperm). Male patients must not donate sperm until 90 days after the last dose of study drug. Adequate contraception for the male patient and his female partner of childbearing potential is defined as using hormonal contraceptives or an intrauterine device, combined with at least one of the following forms of contraception: a diaphragm or cervical cap, or a condom. Total abstinence from heterosexual activity, in accordance with the lifestyle of the patient, is acceptable.
• Diagnosis of moderate to severe UC
• Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
• Patients with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >45 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during Screening).
• Demonstrated an inadequate response to, loss of response to, or intolerance to at least 1 of the following agents:

Corticosteroids, Immunomodulators, TNFα antagonists

• Able to participate in all aspects of this clinical study, including collection of tissue biopsies.
• Male or female patient who is voluntarily able to give informed consent.

(Selected) Exclusion Criteria:

• Previous exposure to vedolizumab (Entyvio® or any other investigational vedolizumab containing product).
• Female patients who are lactating or have a positive serum pregnancy test during the Screening Period or a positive urine pregnancy test on Day 0 prior to study drug administration.
• Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives prior to randomization (whichever is longer).
• Evidence of abdominal abscess or toxic megacolon at the Screening Visit.
• Extensive colonic resection, subtotal or total colectomy.
• History of ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
• History or evidence of colonic mucosal dysplasia.
• Diagnosis of Crohn's disease, microscopic colitis, ischemic colitis or indeterminate colitis.
• Had any surgical procedure requiring general anesthesia within 30 days prior to randomization or the patient currently requires or is anticipated to require surgical intervention for UC during the study.
• Has history or evidence of adenomatous colonic polyps that have not been removed, or colonic mucosal dysplasia.
• Has any of the following:

Evidence of a serious active or clinically significant infection requiring medical treatment or that in the opinion of the Investigator would confound the study results, during Screening or has been hospitalized or treated for such infection within 60 days of Baseline (e.g., sepsis, cytomegalovirus, listeriosis or opportunistic infections such as PML).

OR Evidence of or received treatment for C. difficile infection within 60 days, or other intestinal pathogen within 30 days prior to Screening. Rescreening of treated patients with no clinical signs and subsequent negative test results can be allowed at the Investigator's discretion.

OR Other current or recent (within 30 days prior to Screening) clinically significant infection (e.g., pneumonia, pyelonephritis).

• Chronic hepatitis B or C infection. Patients with positive viral serology at Screening for infection with hepatitis B (HBV), or hepatitis C virus (HCV) may be eligible if polymerase chain reaction test is negative, and the patient receives standard of care antiviral prophylaxis (if applicable).
• Known active TB.
• Has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
• Has a history of hypersensitivity or allergies to the ingredients of Entyvio®.