A study to compare the effect of AVT16 and Entyvio® in subjects with moderate to severe active ulcerative colitis.

Trial details

Who runs it

Alvotech Swiss AG

Trial code

EU 2023-507705-34-00

Record updated

2025. február 5.

Original description

To demonstrate equivalent efficacy of AVT16, a proposed biosimilar to Entyvio.Read full original descriptionShow less

A Parallel-Group Treatment, Double-Blind, 2-Arm Study to Investigate the Comparative Efficacy, Safety, and Immunogenicity Between Intravenous AVT16 and Entyvio® in Male and Female Subjects Aged 18 to 80 Years Inclusive with Moderate to Severe Active Ulcerative Colitis

To demonstrate equivalent efficacy of AVT16, a proposed biosimilar to Entyvio.

Inclusion: Male or female subjects aged 18 to 80 years inclusive at the time of signing the informed consent form (ICF) who are voluntarily able to give informed consent. 2. Female subjects are eligible to participate if they are not pregnant, not breastfeeding, and at least ONE of the following conditions applies: a. Is not a woman of childbearing potential (WOCBP), defined as: i. Surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, as confirmed by review of the subject’s medical records, medical examination, or medical history interview), or ii. Postmenopausal (defined as no menses for 12 months without an alternative medical cause). A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy (HRT). However, in the absence of 12 months of amenorrhea, confirmation with more than 1 FSH measurement is required. Female subjects on HRT and whose menopausal status is in doubt will be required to use 1 of the nonestrogen hormonal highly effective contraception methods from screening (signing the ICF) until at least 18 weeks after the last investigational product (IP) administration if they want to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. b. Is a WOCBP who agrees to use a highly effective method of contraception consistently and correctly from screening (signing the ICF) until at least 18 weeks after the last IP administration and agrees not to donate or cryopreserve ova during the course of the study and for at least 18 weeks after the last IP administration. 3. Nonsterilized male subjects with female partners of childbearing potential are eligible to participate if they agree to 1 of the following from screening (signing the ICF) until at least 18 weeks after the last IP administration: a. Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent. b. Agree to use a male condom with spermicide and have their partner use a contraceptive method with a failure rate of less than 1% per year when having penile vaginal intercourse with a WOCBP who is not currently pregnant. c. Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom with spermicide during each episode of penile penetration. d. In addition, male subjects must refrain from donating sperm from screening (signing the ICF) until at least 18 weeks after the last IP administration. 4. Diagnosis of UC 5. Moderately to severely active UC 6. Evidence of UC 7. Subjects with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during screening). 8. Subjects with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or another known risk factor must be up to date on colorectal cancer surveillance (may be performed during screening). 9. Demonstrated, over the previous 5-year period, an inadequate response to, loss of response to, or intolerance of at least 1 of the following agents as defined below: 10. May be receiving a therapeutic dose of the following drugs: a. Oral 5-aminosalicylic acid (5-ASA) compounds provided b. Oral corticosteroid therapy c. Probiotics (eg, Culturelle, Saccharomyces boulardii) d. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea. e. Azathioprine or 6-mercaptopurine provided For the complete list please refer to protocol.

Exclusion: Evidence of abdominal abscess or toxic megacolon or fulminant stage of disease during the screening period. 2. Extensive colonic resection, subtotal, or total colectomy. 3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. 4. Prior treatmentfor UC. 5. Have received any of the following for the treatment: a. Other than those permitted in the study if last dose was given prior to the baseline endoscopy. 6. Use of topical (rectal) treatment prior to baseline endoscopy. 7. Evidence of or treatment prior to baseline endoscopy. 8. Currently require or are anticipated to require surgical intervention for UC during the study. 9. History or evidence of adenomatous colonic polyps that have not been removed. 10. History or evidence of any grade of colonic mucosal dysplasia. 11. Diagnosis of Crohn’s colitis or indeterminate colitis. Infectious Disease Exclusion Criteria 12. Chronic hepatitis B or C infection: Subjects with evidence of positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Hepatitis B virus (HBV) immune subjects (ie, HBsAg-negative and hepatitis B antibody–positive) may, however, be included. Note: If a subject tests negative for HBsAg, but positive for HBcAb, the subject would be considered eligible if the absence of HBV DNA is confirmed by HBV DNA polymerase chain reaction reflex testing performed in the central laboratory. Subjects with chronic hepatitis C virus (HCV) (ie, positive HCV antibody [HCVAb] and HCV RNA). Note: Subjects who are HCVAb positive without evidence of HCV RNA may be considered eligible in the event of spontaneous viral clearance or previously treated and cured (defined as no evidence of HCV RNA at least 12 weeks before baseline). 13. Active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following: a. History of TB. b. A positive diagnostic TB test within 1 month of enrollment defined as: i. a positive QuantiFERON® test or 2 successive indeterminate QuantiFERON tests c. Chest X-ray within 3 months of enrollment in which active or latent pulmonary TB cannot be excluded Note: Subjects with an indeterminate QuantiFERON test are allowed if they have all of the following d. No evidence of active TB on chest radiograph within 3 months prior to the first dose of IP e. Documented history of 3 weeks of prophylaxis initiation prior to receiving IP in accordance with local recommendations and intends to complete its entire course during the study f. No known exposure to active TB after most recent prophylaxis g. Asymptomatic at screening and baseline Investigators should check with the medical monitor before enrolling such subjects 14. Any identified congenital or acquired immunodeficiency 15. Any live vaccinations within 30 days prior to IP administration except for an influenza vaccine 16. Clinically significant extra-intestinal infection within 30 days prior to baseline endoscopy 17. Previous exposure to vedolizumab 18. Female subjects 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 IP administration 19. Any unstable or uncontrolledmedical disorder that, in the opinion of the investigator, would confound the study results or compromise subject safety 20. Have had any surgical procedure requiring general anesthesia within 30 days prior to baseline endoscopy or are planning to undergo major surgery during the study period 21. Any history of malignancy, except for the following: (a) adequately treated nonmetastatic basal cell skin cancer; (b) any other type of nonmelanoma skin cancer that has been adequately treated and has not recurred for at least 5 years prior to baseline endoscopy; and (c) adequately treated in situ cervical cancer that has not recurred for at least 5 years prior to baseline endoscopy 22. History of any major neurological disorders For the complete list please refer to protocol.

EU CTIS 2023-507705-34-00