CTRI/2023/10/058307 [Registered on: 05/10/2023] Trial Registered Prospectively
Last Modified On:
28/02/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug Biological
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
PB016 and Entyvio® in the induction and maintenance of clinical response and remission in adults with moderately to severely active ulcerative colitis.
Scientific Title of Study
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)
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Shamim Anwar
Designation
Senior Project Manager
Affiliation
Worldwide Clinical Trials India Pvt. Ltd,
Address
Worldwide Clinical Trials India Pvt. Ltd, Unit No. 09 9th Floor, Corporate Park II, VN Purav Marg, Near Swastik Chambers, Swastik Park, Chembur, Mumbai
Worldwide Clinical Trials India Pvt. Ltd, Unit No. 09 9th Floor, Corporate Park II, VN Purav Marg, Near Swastik Chambers, Swastik Park, Chembur, Mumbai
Worldwide Clinical Trials India Pvt. Ltd, Unit No. 09 9th Floor, Corporate Park II, VN Purav Marg, Near Swastik Chambers, Swastik Park, Chembur, Mumbai
Mumbai MAHARASHTRA 400071 India
Phone
Fax
Email
mohit.sharma@worldwide.com
Source of Monetary or Material Support
Polpharma Biologics S.A.
Trzy Lipy 3
80-172 Gdansk Poland
Primary Sponsor
Name
Polpharma Biologics S.A.
Address
Trzy Lipy 3 80-172 Gdansk Poland
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Worldwide Clinical Trials India Pvt Ltd
Unit No 09, 9th Floor,
Corporate Park II, VN Purav Marg, Near Swastik Chambers, Swastik
Park, Chembur East, Mumbai, MAHARASHTRA 400071, India
Countries of Recruitment
Turkey Slovakia South Africa Hungary India Israel Latvia Poland Romania Australia Bosnia and Herzegovina Brazil Bulgaria Czech Republic Georgia Albania
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 on Weeks 6, 14, 22, 30, 38, and 46.
Intervention
PB016
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 on Weeks 6, 14, 22, 30, 38, and 46.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. 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.2.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. Adequatecontraception 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, inaccordance with the lifestyle of the patient, is acceptable.3. 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.4. 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.5. Moderately to severely active UC as determined by a complete Mayo score of 6 to 12 with an endoscopic sub-score is more than or equal to 2, confirmed by a central reader within 28 days prior to randomization.6. Evidence of UC extending proximal to the rectum (is greater than or equal to 15 cm of involved colon).7. Patients with extensive colitis or pancolitis of greater than 8 years duration or left-sided colitis of greater than 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. Patients with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age greater than 45 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during Screening).
ExclusionCriteria
Details
1. Previous exposure to vedolizumab (Entyvio® or any other investigational vedolizumab containing product).
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
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 8.
b. A non-biologic investigational therapy
c. An approved non-biologic therapy in an investigational protocol
4. Has received any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives prior to randomization (whichever is longer)
5. Has had prior exposure to approved or investigational anti-integrin antibodies (e.g., natalizumab, efalizumab, etrolizumab, AMG-181, anti-MAdCAM-1 antibodies) or antiCD20 antibodies (e.g., rituximab)
6. Evidence of abdominal abscess or toxicmegacolon at the Screening Visit.
7. Extensive colonic resection, subtotal or total colectomy
8. History of ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine
9. Diagnosis of Crohn’s disease, microscopic colitis, ischemic colitis or indeterminate colitis.
10. 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
11. Has any identified congenital or acquired immunodeficiency
(e.g., common variable immunodeficiency, human
immunodeficiency virus [HIV] infection, organ transplantation).
12. Has any live vaccination within 30 days prior to Screening or is
planning to receive any live vaccination during participation in
the study
13. 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
14. Has any unstable or uncontrolled cardiovascular disorder, heart
failure moderate to severe (New York Heart Association Class III
or IV), any pulmonary, hepatic, renal, GI, 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
15. Has received total parenteral nutrition or albumin in the last 30
days prior to randomization.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
To demonstrate similarity of effect of
induction treatment with IV formulations of
PB016 & Entyvio® on clinical response rate
at 6 weeks
Clinical response rate, defined as the proportion of patients with a reduction in
complete Mayo score of greater than or equal to 3 points & greater than or equal to 30%
from Baseline with an accompanying decrease
in rectal bleeding (RB) sub-score of greater than or equal to 1 point
or absolute RB sub-score of less than or equal to 1 point, at Week 6
Secondary Outcome
Outcome
TimePoints
To demonstrate similarity of effect of
maintenance treatment with IV formulations
of PB016 & Entyvio® on clinical response
rate at 52 weeks
Clinical response rate at Week 52
To demonstrate similarity of effect of IV
PB016 & Entyvio® on partial Mayo score
Change from Baseline in partial Mayo score
at Weeks 2, 6, 14, 22, 30, 38, 46, & 52
To demonstrate similarity of effect of IV PB016 & Entyvio® on clinical remission rate
Clinical remission rate, defined as the proportion of patients with complete Mayo score of less than or equal to 2 points & no individual sub-score 1 point, at Weeks 6, and 52.
To demonstrate similarity of effect of IV PB016 & Entyvio® on mucosal healing rate
Mucosal healing rate, defined as the proportion of patients with a Mayo endoscopic sub-score of less than or equal to 1 point, at Weeks 6, and 52
To demonstrate similarity of effect of IV
PB016 & Entyvio® on corticosteroid-free
remission rate
Corticosteroid-free remission rate, defined as
the proportion of patients using oral
corticosteroids at Baseline who have
discontinued corticosteroids & are in clinical
remission at Week 52
To demonstrate similarity of IV PB016 and
Entyvio® on immunogenicity
Number of patients with anti-drug antibodies
(ADAs) & neutralizing antibodies (NAb) at
Baseline and at Weeks 2, 6, 14, 30, and 52
Total Sample Size="750" Sample Size from India="350" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This randomized, double-blind, multicenter, phase 3 study is designed to compare clinical efficacy, safety, and immunogenicity of 300 mg IV formulation of PB016 with Entyvio® in patients with UC. The aim of the study is to show similarity between vedolizumab (Entyvio®) and PB016 in induction and maintenance of clinical response and remission of UC. This study is part of a tailored clinical development program to support biosimilar development of PB016 data. Polpharma Biologics is developing the proposed vedolizumab biosimilar product, PB016, for the same indications as approved for the reference product. PB016 approval will provide alternative treatment options for affected individuals and their healthcare providers.