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®.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Polpharma Biologics S.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Nov 2023 → 2 Apr 2026

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ORG-100014496

External identifiers

EU CT number

2022-502778-18-00

WHO UTN

U1111-1289-2771

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Bioequivalence, Efficacy, Pharmacokinetic, Safety

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

Secondary objectives 9

1. 1. To demonstrate similarity of effect of maintenance treatment with IV formulations of PB016 and Entyvio® on clinical response rate at 52 weeks
2. 2. To demonstrate similarity of effect of IV PB016 and Entyvio® on partial Mayo score
3. 3. To demonstrate similarity of effect of IV PB016 and Entyvio® on clinical remission rate
4. 4. To demonstrate similarity of effect of IV PB016 and Entyvio® on mucosal healing rate
5. 5. To demonstrate similarity of effect of IV PB016 and Entyvio® on corticosteroid-free remission rate
6. 6. To demonstrate similarity of effect of IV PB016 and Entyvio® on disease-related biomarkers
7. 7. To demonstrate similarity of IV PB016 and Entyvio® on pharmacokinetics
8. 8. To compare the safety profiles of PB016 and Entyvio®
9. 9. To demonstrate similarity of IV PB016 and Entyvio® on immunogenicity

Conditions and MedDRA coding

ulcerative colitis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Age ≥18 and ≤80 years at Screening.
2. 10. 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).
3. 11. 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.
4. 12. Able to participate in all aspects of this clinical study.
5. 13. Male or female patient who is voluntarily able to give informed consent.
6. 2. 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.
7. 3. 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.
8. 4. 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.
9. 5. 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.
10. 6. 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.
11. 7. Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
12. 8. 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).
13. 9. 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).
14. 14. Body mass index ≥18 at Screening.

Exclusion criteria 28

1. 1. Previous exposure to vedolizumab (Entyvio® or any other investigational vedolizumab-containing product).
2. 10. Diagnosis of Crohn’s disease, microscopic colitis, ischemic colitis or indeterminate colitis.
3. 11. 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.
4. 12. Has history or evidence of adenomatous colonic polyps that have not been removed.
5. 13. 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).
6. 14. 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).
7. 15. 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.
8. 16. Has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency, human immunodeficiency virus infection, organ transplantation).
9. 17. 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.
10. 18. Has any live vaccination within 30 days prior to Screening or is planning to receive any live vaccination during participation in the study.
11. 19. 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.
12. 2. 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.
13. 20. Has a history of hypersensitivity or allergies to the ingredients of Entyvio®.
14. 21. 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.
15. 22. Positive PML subjective symptom checklist prior to the administration of the first dose of study drug.
16. 23. Current or recent history (within 1 year prior to randomization) of alcohol dependence or illicit drug abuse.
17. 24. Active psychiatric problems that, in the Investigator’s opinion, may interfere with compliance with the study procedures.
18. 25. 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.
19. 26. Has received total parenteral nutrition or albumin in the last 30 days prior to randomization.
20. 27. 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.
21. 28. 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.
22. 3. 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.
23. 4. 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).
24. 5. 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).
25. 6. Evidence of abdominal abscess or toxic megacolon at the Screening Visit.
26. 7. Extensive colonic resection, subtotal or total colectomy.
27. 8. History of ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
28. 9. History or evidence of colonic mucosal dysplasia.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Clinical response rate, defined as the proportion of patients with a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline* with an accompanying decrease in rectal bleeding (RB) sub-score of ≥1 point or absolute RB sub-score of ≤1 point, at Week 6. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.

Secondary endpoints 9

1. 1. Clinical response rate at Week 52
2. 2. Change from Baseline* in partial Mayo score at Weeks 2, 6, 14, 22, 30, 38, 46, and 52. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.
3. 3. Clinical remission rate, defined as the proportion of patients with complete Mayo score of ≤2 points and no individual sub-score >1 point, at Weeks 6 and 52
4. 4. Mucosal healing rate, defined as the proportion of patients with a Mayo endoscopic sub-score of ≤1 point, at Weeks 6 and 52
5. 5. Corticosteroid-free remission rate, defined as the proportion of patients using oral corticosteroids at Baseline* who have discontinued corticosteroids and are in clinical remission at Week 52. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.
6. 6. Change from Baseline* in fecal calprotectin at Weeks 6, 22, and 52; Change from Baseline* in blood C-reactive protein (CRP) at Weeks 6, 22, and 52. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.
7. 7. Vedolizumab (Ctrough) levels at Baseline*, Weeks 2, 6, 14, 22, 30, 38, and 52. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.
8. 8. Number of patients with adverse events (AEs) and serious adverse events (SAEs); Number of patients discontinuing treatment due to AEs or SAEs
9. 9. Number of patients with anti-drug antibodies (ADAs) and neutralizing antibodies (NAb) at Baseline* and at Weeks 2, 6, 14, 30, and 52. *Visit 1 (Day 0) is to be considered Baseline unless the assessment is not performed at Visit 1. In such cases, the Screening assessment is to be considered Baseline.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Polpharma Biologics S.A.

Sponsor organisation

Polpharma Biologics S.A.

Address

Ul. Trzy Lipy 3

City

Gdansk

Postcode

80-172

Country

Poland

Scientific contact point

Organisation

Polpharma Biologics S.A.

Contact name

Agnes

Public contact point

Organisation

Polpharma Biologics S.A.

Contact name

Agnes

Third parties 4

Locations

7 EU/EEA countries · 67 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 72 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications