A study in people with moderately to severely active ulcerative colitis to see how well an investigational treatment called PB016 works and how safe it is compared to a licensed treatment called Entyvio®.

Trial details

Who runs it

Polpharma Biologics S.A.

Trial code

EU 2022-502778-18-00

Record updated

2026. január 19.

Original description

To demonstrate similarity of effect of induction treatment with (intravenous) IV formulations of PB016 and Entyvio® on clinical response rate at 6 weeksRead full original descriptionShow less

A randomized, double-blind, multicenter phase 3 study in patients with moderately to severely active ulcerative colitis (UC) to compare the efficacy, safety and immunogenicity of PB016 and Entyvio® for the induction and maintenance of clinical response and remission. (UCESIVE)

To demonstrate similarity of effect of induction treatment with (intravenous) IV formulations of PB016 and Entyvio® on clinical response rate at 6 weeks

Inclusion: Age ≥18 and ≤80 years at Screening; Moderately to severely active UC as determined by a complete Mayo score of 6 to 12 with an endoscopic sub-score ≥2, confirmed by a central reader within 28 days prior to randomization; Evidence of UC extending proximal to the rectum (≥15 cm of involved colon); Patients 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); 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); Body mass index ≥18 at Screening; Demonstrated an inadequate response to, loss of response to, or intolerance to at least 1 of the following agents: Corticosteroids Signs and symptoms of persistently active disease despite a history of at least one 4-week induction regimen that included a dose equivalent to prednisone 30 mg daily orally for 2 weeks or intravenously for 1 week. OR Two failed attempts to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally (i.e., corticosteroid dependent patients). OR History of intolerance to corticosteroids (including, but not limited to Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection). Immunomodulators Signs and symptoms of persistently active disease despite a history of at least one 8-week regimen of oral azathioprine (≥1.5 mg/kg) or 6-mercaptopurine mg/kg (≥0.75 mg/kg). OR History of intolerance to at least one immunomodulator (including, but not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function test abnormalities, lymphopenia, TPMT genetic mutation, infection). Tumor Necrosis Factor Alpha (TNFα) Antagonists Non-responders/inadequate response despite a history of at least one induction regimen/loading dose of TNFα antagonists as per summary of product characteristics (SmPC). OR Recurrence of symptoms during maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify). OR History of intolerance to TNFα antagonists (including, but not limited to site/infusion-related reaction, demyelination, congestive heart failure, infection); May be receiving a therapeutic dose of the following drugs: a. Oral 5-aminosalicylic acid (5-ASA) compounds provided that the dose has been stable for the 2 weeks prior to randomization. b. Oral corticosteroid therapy (at a dose of ≤30 mg/day prednisone equivalent) provided that the dose has been stable for the 4 weeks immediately prior to randomization (if corticosteroids have just been initiated), or for the 2 weeks immediately prior to randomization (if corticosteroids are being tapered). c. Probiotics (e.g., Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks immediately prior to randomization. d. Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) for control of chronic diarrhea. e. Azathioprine or 6-mercaptopurine provided that the dose has been stable for the 8 weeks immediately prior to randomization; Able to participate in all aspects of this clinical study; Male or female patient who is voluntarily able to give informed consent; 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 postmenopausal [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 highly effective contraception from Screening until 18 weeks after the last dose of study drug; 4. Male patients engaging in sexual intercourse with a female of childbearing potential must agree they will use condoms with spermicide or abstain from sexual intercourse for the duration of the study, starting at Screening and for at least 18 weeks after their 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 18 weeks after the last dose of study drug; Diagnosis of moderate to severe UC established at least 6 months prior to Screening by clinical and endoscopic evidence, corroborated by a histopathology report and confirmed by the Investigator.

Exclusion: Previous exposure to vedolizumab (Entyvio® or any other investigational vedolizumab-containing product); Has any live vaccination within 30 days prior to Screening or is planning to receive any live vaccination during participation in the study; Has used a topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks prior to randomization unless taken on stable dose for at least 2 weeks before randomization; Positive PML subjective symptom checklist prior to the administration of the first dose of study drug; Current or recent history (within 1 year prior to randomization) of alcohol dependence or illicit drug abuse; Within 30 days prior to randomization, has received any of the following for the treatment of underlying disease: a. Non-biologic therapies (e.g., cyclosporine, thalidomide) other than those specifically listed in Inclusion Criterion 11. b. A non-biologic investigational therapy. c. An approved non-biologic therapy in an investigational protocol; Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives, prior to randomization (the choice is based on the Investigator’s discretion); Has had prior exposure to approved or investigational anti integrin antibodies (e.g., natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1 antibodies) or anti-CD20 antibodies (e.g., rituximab); Extensive colonic resection, subtotal or total colectomy; 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; 13. 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 progressive multifocal leukoencephalopathy [PML]). OR Evidence of C. difficile or other intestinal pathogen at Screening. If during Screening, patients tested positive for C. difficile or any other stool pathogens, retest for the same pathogen can be performed at the Investigator’s discretion (e.g., if there is a doubt or reasonable expectation for a negative outcome of the retest). In case of screen failure, rescreening of patients with completed treatment against the pathogen 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); Known active tuberculosis (TB). OR Positive QuantiFERON® test or 2 successive indeterminate QuantiFERON® tests. OR Chest X-ray within 3 months of randomization in which active or latent pulmonary TB cannot be excluded. OR A tuberculin skin test reaction ≥10 mm (≥5 mm in patients receiving the equivalent of >15 mg/day prednisone). Note: Patients currently receiving treatment for latent TB without active TB, or patients with a positive QuantiFERON® or tuberculin test but where active TB is ruled out and standard of care anti-TB treatment has been initiated will not be excluded from the study; Has a history of hypersensitivity or allergies to the ingredients of Entyvio®; History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease that, in the opinion of the Investigator, would confound the study results; Active psychiatric problems that, in the Investigator’s opinion, may interfere with compliance with the study procedures; Diagnosis of Crohn’s disease, microscopic colitis, ischemic colitis or indeterminate colitis; Has any unstable or uncontrolled cardiovascular disorder, heart failure moderate to severe (New York Heart Association Class III or IV), any pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the Investigator, would confound the study results or compromise patient safety; History of ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine; Chronic hepatitis B or C infection. Patients with positive viral serology at Screening for infection with hepatitis B, or hepatitis C virus may be eligible if polymerase chain reaction test is negative, and the patient receives standard of care antiviral prophylaxis (if applicable); Has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus infection, organ transplantation); 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; Any of the following laboratory abnormalities during the Screening Period: a. Hemoglobin level <8 g/dL. b. White blood cell count <3 × 109/L. c. Lymphocyte count <0.5 × 109/L. d. Platelet count <100 × 109/L or >1200 × 109/L. e. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN). f. Alkaline phosphatase >3 × ULN. g. Serum creatinine >2 × ULN; Has received total parenteral nutrition or albumin in the last 30 days prior to randomization; Any history of malignancy, except for the following: a. Adequately treated nonmetastatic basal cell skin cancer. b. Squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to randomization. c. History of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to randomization. Note: Patients with remote history of malignancy (e.g., >5 years since completion of curative therapy without recurrence prior to Screening) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the Sponsor on a case-by-case basis prior to randomization; Any persons who are: a. An employee of the study site, Investigator, CRO or Sponsor. b. A first-degree relative of an employee of the study site, the Investigator, CRO, or Sponsor. c. Unable to attend all the study visits or comply with study procedures; Evidence of abdominal abscess or toxic megacolon at the Screening Visit; History or evidence of colonic mucosal dysplasia; Has history or evidence of adenomatous colonic polyps that have not been removed.

EU CTIS 2022-502778-18-00