CTRI/2025/02/080437尚未招募3 期
A Phase 3, Randomized, Double-Blind, Multicenter, Active- Controlled, Two-Arm, Parallel Group Study to Compare the Efficacy, Safety, Immunogenicity and Pharmacokinetics of the Proposed Biosimilar of Vedolizumab (INTP53) Intravenous Injection and Vedolizumab Reference for Induction and Maintenance Therapy in Patients with Moderate to Severe Active Ulcerative Colitis
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 214
- 试验地点
- 28
- 主要终点
- To establish non-inferiority for the clinical response rates associated with vedolizumab-test compared to vedolizumab-reference at Week 6 in participants with moderately to
研究概览
简要总结
This is a study to Compare the Efficacy, Safety, Immunogenicity and Pharmacokinetics of Biosimilar Vedolizumab Injection in Patients with Moderate to Severe Active Ulcerative Colitis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 盲法
- Double
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in section 10.1.3 and in this protocol and is willing to participate in the study.
- •2 Male or female participants with 18 completed years of age or older at the time of signing the informed consent.
- •3 Participants must have a documented diagnosis of UC at least three months duration before screening, confirmed by:Medical records with a report of an endoscopy, which shows features consistent with UC, as determined by the procedure performing physician, AND Medical record documentation of a histopathology report showing features consistent with UC, as determined by the local pathologist.
- •Note: If a histopathology report is unavailable, histologic samples can be obtained at the screening endoscopy and sent to a local laboratory to confirm UC diagnosis before randomization.
- •The screening endoscopy must show features consistent with UC, and medical records must still document a clinical diagnosis of UC at least three months duration before screening.
- •4 Participant has moderately to severely active UC as defined by a Complete Mayo score of 6 to 12 (both inclusive) with an endoscopic subscore (ES) greater than or equal to 2 (with endoscopy performed within ten days before the first dose of investigational intervention), a rectal bleeding subscore greater than or equal to 1, and a stool frequency subscore greater than or equal to 1 during the screening period (before randomization on Day 1).
- •5 Participants have evidence of UC extending proximal to the rectosigmoid junction (greater than or equal to 15 cm of the involved colon from the anal margin) as determined by screening endoscopy.
- •Participants with rectal sparing on screening endoscopy must have documentation of rectal involvement on a prior endoscopy and histopathology report to confirm UC diagnosis.
- •6 Have documentation of:A surveillance colonoscopy for dysplasia (performed according to local standards) within 12 months before the first administration of investigational intervention for: a participants with pancolitis of greater than 8 years duration or a participants with left-sided colitis of greater than 12 years of duration or a participants with primary sclerosing cholangitis.
- •OR Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age greater than 50 years, or other known risk factors must either have had a full colonoscopy to assess for the presence of adenomatous polyps within five years before the first administration of investigational intervention.
- •Participants who do not have a colonoscopy report available in source documentation must have a colonoscopy at screening.
- •7 Participants must have an inadequate response to, loss of response to, or intolerance to a treatment course of one or more of the following standard of care medications described below as A OR B.
- •Documentation of dose, dates, frequency, route of administration, and duration of the prior failed treatment, as well as documents that the participant had persistent disease activity UC treatment, is required.
- •Signs and symptoms of persistently active disease for this inclusion criteria are defined as the lack of improvement or worsening of at least 1 of the following: stool frequency, rectal bleeding, daily abdominal pain, worsening in urgency, and endoscopic appearance of the colonic mucosa.
- •These signs and symptoms of UC are offered only as a benchmark of the minimally acceptable criteria.
- •The ultimate decision to reduce the dose or discontinue UC drugs due to intolerance remains at the discretion of the investigator.
- •8 A female participant is eligible to participate if she is not pregnant or breastfeeding and at least one of the following conditions applies 9 Participants with adequate haematology, liver and renal function at screening visit: a.
- •Total WBC count greater than or equal to 3000 per cu.mm b.
- •Absolute neutrophil count greater than or equal to 1000 per cu.mm c.
- •Absolute lymphocyte count greater than or equal to 500 per cu.mm d.
- •Hb greater than or equal to 8 g per dL e.
- •Platelet count greater than or equal to 100,000 per cu.mm f.
- •AST AND ALT less than or equal to 3 into ULN g.
- •Total bilirubin less than or equal to 1.5 into ULN (isolated total bilirubin greater than 1.5 into ULN is allowed for those participants with known Gilberts syndrome; Gilberts syndrome is suggested by direct bilirubin less than 30 percent).
- •Creatinine less than or equal to 2 into ULN 10 Willing and able to adhere to the lifestyle restrictions specified in this protocol.
- •11 Each potential participant must satisfy all of the following criteria to be enrolled in the study: Must be able to read, understand, and complete the patient diary.
- •Must intend to comply with the completion of the patient diary.
排除标准
- •1 Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal other than ulcerative colitis, endocrine, neurologic, haematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
- •2 Known history of serious or severe allergies, hypersensitivity, or intolerance to any chimeric, human, or humanized antibodies, fusion proteins, or murine proteins OR to investigational interventions, components/ excipients thereof (L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, Sucrose, Polysorbate 80), OR any other drug allergy that, in the opinion of the investigator, contraindicates participation in the study.
- •3 Contraindications to the use of any of the investigational interventions or components/excipients per DCGI approved PI of Kynteles[3] or SmPC of Entyvio [1] 4 Participant has one or more of the following gastrointestinal conditions with documented evidence at the screening visit a.
- •Have a current diagnosis of Crohn’s disease or inflammatory bowel disease unclassified (IBD-U) (formerly known as indeterminate colitis), ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis or any other abnormality which may affect the objective assessment as per PI’s judgment b.
- •Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy).
- •Previous bowel resection or intestinal or intra-abdominal surgery.
- •Presence of a stoma.
- •Presence or history of a fistula.
- •Current or recent (within 12 weeks before the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation.
- •Any history or current evidence of cancer of the gastrointestinal tract.
- •5 Has prior or current evidence of definite low-grade or high-grade colonic dysplasia including dysplasia identified during the screening endoscopy that has not been completely removed.
- •Once completely removed, the participant is eligible for the study.
- •6 Has severe extensive colitis as evidenced by: 7 Exclusion Criteria Related to Prior or Concomitant Therapy 8 Participants with ongoing/inadequately treated serious, opportunistic or chronic/recurring extraintestinal infections at screening visit including but not limited to the following.
- •9 Any current signs or symptoms of active extraintestinal infection within two weeks before the first dose of study intervention, except for the following: 10 Have evidence of active infectious herpes zoster infection less than or equal to 8 weeks before screening.
- •Herpes zoster infections remain active until all vesicles are crusted over.
- •11 Had evidence of treatment for Clostridium difficile within 4 weeks of the first dose of investigational intervention or test positive for C.
- •If a participant is positive for C.
- •difficile at screening, the participant may be treated and rescreened less than or equal to 4 weeks after completing treatment.
- •12 Clinically significant abnormalities on screening neurologic examination (PML Objective Checklist and PML Subjective Checklist).
- •Participant may be rescreened once PML is ruled out conclusively by neurologist.
- •13 Presence of current acute or chronic hepatitis B infection or test positive for hepatitis B virus (HBV) at screening.
- •Refer to Appendix 7 for eligibility based on the HBV serologic markers.
- •14 Presence of current hepatitis C infection or test positive for hepatitis C virus (HCV) at screening.
- •15 Has known human immunodeficiency virus (HIV) seropositive status or positive HIV antibody test at screening.
- •16 The participant has any identified congenital or acquired immunodeficiency (e.g., common variable immunodeficiency).
- •17 Have evidence of active or latent infection with Mycobacterium tuberculosis (TB) as defined by either of the following.
- •18 Evidence of or treatment for clinically significant cytomegalovirus (CMV) colitis (based on the investigator’s judgment) within 60 days before the first dose of investigational intervention.
- •Laboratory confirmation of CMV from colon biopsy is required during screening evaluation only if clinical suspicion is high.
- •Participants with a confirmed diagnosis of cytomegalovirus-associated colitis should have adequate treatment and resolution of symptoms at least three months before the first dose of investigational intervention.
- •19 Participants who have received any live vaccinations within four weeks before the first dose of the investigational intervention or intend to receive such during the study.
- •20 Have a solid organ transplant (except for a corneal transplant performed greater than 12 weeks before screening) or hematopoietic stem cell transplantation.
- •22 History of malignancy within the past five years except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least three years since initiating that therapy.
- •Note: The time requirement does not apply to participants with basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers who underwent successful definitive resection with no evidence of metastatic disease which is considered cured with minimal risk of recurrence.
- •23 Received an investigational intervention or used an invasive investigational medical device within 30 days or five half-lives before the first dose of investigational intervention, whichever is longer, before signing the consent or is currently enrolled in an investigational study.
- •24 Participants with uncontrolled hypertension (systolic greater than 140 mm Hg or diastolic greater than 90 mm Hg) despite optimal antihypertensive treatment at screening.
- •If blood pressure is out of range, up to 2 repeated assessments are permitted no more than 60 minutes apart.
- •Note: Participants may be retested or rescreened after initiation or adjustments of antihypertensive medications to establish control.
- •25 Participants with uncontrolled diabetes mellitus (defined as HbA1c greater than 8 percent) at screening.
- •26 The participant with a systolic blood pressure of less than 90 mmHg at screening.
- •Note: Participants may be retested or rescreened after correction of blood pressure.
结局指标
主要结局
To establish non-inferiority for the clinical response rates associated with vedolizumab-test compared to vedolizumab-reference at Week 6 in participants with moderately to
时间窗: Week 0, Week 2, Week 6, Week 14, Week 22 and Week 26 / EOS visit
severely active ulcerative colitis
时间窗: Week 0, Week 2, Week 6, Week 14, Week 22 and Week 26 / EOS visit
次要结局
- To further evaluate the efficacy of(vedolizumab-test compared to)
研究者
Dr Naman Shah
Lambda Therapeutic Research Ltd
研究点 (28)
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