Evaluation of Vedolizumab in Achieving Corticosteroid-Free Remission in Patients with Moderately to Severely Active Ulcerative Colitis: A Randomized Controlled Trial
- Trial ID
- 2024-514183-21-00
- Protocol
- RP1706
- Sponsor
- Alimentiv Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to determine whether, in subjects with moderately to severely active **ulcerative colitis** (UC), achieving a target of corticosteroid-free symptomatic, endoscopic, and histological remission is superior to a target of corticosteroid-free symptomatic remission. This is evaluated in terms of the primary endpoint, which is the time to UC-related complication within up to 80 weeks of follow-up after achieving the target. This objective is clinically relevant as it aims to establish a more comprehensive treatment target that could potentially lead to better long-term outcomes for patients with UC.
Secondary objectives include:
- Evaluating the time to UC-related complication in the full analysis set, including subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target.
- Assessing whether treatment to the target of symptomatic and endoscopic remission is superior to symptomatic remission alone in terms of the primary endpoint.
- Determining if treatment to the target of corticosteroid-free symptomatic, endoscopic, and histological remission is superior to corticosteroid-free symptomatic and endoscopic remission.
- Evaluating the time to UC-related complication in subjects who exclusively reach their assigned target by Week 48.
- Assessing the time taken to achieve the respective targets among the randomized groups.
- Evaluating the time to each type of UC-related complication across the target achievement groups.
- Assessing the effect of treatments on UC-related complications mediated through treatment targets.
- Evaluating changes in fecal calprotectin levels, C-reactive protein concentration, UC-100 score, health-related quality of life using the Inflammatory Bowel Disease Questionnaire, and Work Productivity and Activity Impairment-UC questionnaire from baseline to follow-up visits.
- Evaluating changes in Mayo Clinic Score, Geboes scores, Robarts Histopathology Index scores, and Nancy Histological Index scores from baseline to specified visits.
- Evaluating the numbers of adverse events (AEs) and serious adverse events (SAEs) among the randomized groups.
- Exploring urine, stool, colonic mucosa, and serum samples for biomarkers and drug concentrations associated with clinically important outcomes.
- Validating the Symptoms and Impacts Questionnaire for UC (SIQ-UC) tool in English-fluent subjects.
Participants
The clinical trial involves a total of **281 participants** diagnosed with **ulcerative colitis**. The study population includes both male and female subjects aged 18 years and older, with no vulnerable populations selected. Participants are required to have a confirmed diagnosis of moderately to severely active ulcerative colitis, characterized by specific clinical, endoscopic, and histological criteria. The trial population was selected based on their ability to participate fully in all aspects of the clinical trial, and they must be up to date with colorectal carcinoma surveillance according to local standards. Lifestyle considerations such as diet and physical activity are not specified, but participants must agree to use adequate contraception if of childbearing potential and sexually active. Key inclusion criteria include a Mayo rectal bleeding subscore of at least 1 and a Mayo endoscopic subscore of at least 2, with a minimum disease extent of 15 cm. Participants must also have negative standard of care tests for tuberculosis and hepatitis B and C prior to randomization.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy of treatment strategies in patients with moderately to severely active **ulcerative colitis**. This is a randomized, controlled trial with a double-blind design, ensuring that neither the participants nor the investigators are aware of the treatment assignments. The trial aims to determine whether achieving a target of corticosteroid-free symptomatic, endoscopic, and histological remission is superior to achieving only corticosteroid-free symptomatic remission. The primary endpoint is the time to a **ulcerative colitis**-related complication within up to 80 weeks of follow-up after achieving the treatment target.
Participants will be involved in the study for a maximum of 96 weeks, with the trial estimated to conclude by April 2026. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor progress and collect data, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be at least 18 years old, have a confirmed diagnosis of **ulcerative colitis**, and meet specific disease activity criteria. Participants must also agree to use adequate contraception and refrain from participating in other investigational trials during the study period.
Study visits are structured to ensure comprehensive data collection and participant safety. The screening visit will include assessments such as endoscopic imaging and laboratory tests to confirm eligibility. Follow-up visits will occur at regular intervals to monitor disease activity, treatment response, and any adverse events. The end-of-study visit will involve a final evaluation of the treatment's impact on disease progression and quality of life. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to the study protocol, or choose to withdraw consent.
The trial employs two formulations of **vedolizumab**: a 300 mg powder for concentrate for solution for infusion and a 108 mg solution for injection in a pre-filled syringe. The maximum treatment period for the infusion is 96 weeks, while the injection is limited to 80 weeks. The study's rigorous design and comprehensive data collection aim to provide valuable insights into optimizing treatment targets for **ulcerative colitis**.
Treatment
The clinical trial involves the administration of **Entyvio 300 mg powder for concentrate for solution for infusion**, which contains the active substance **vedolizumab**. This pharmaceutical form is a powder that is reconstituted to form a solution for intravenous infusion. The maximum daily dose is 300 mg, with a total maximum dose of 7200 mg over a treatment period of up to 96 weeks. The administration route is via intravenous infusion, and the frequency of administration is determined by the study protocol. Participant compliance is monitored through scheduled visits and infusion records.
Additionally, the trial includes the use of **Entyvio 108 mg solution for injection in pre-filled syringe**, also containing **vedolizumab**. This formulation is a ready-to-use solution for subcutaneous injection. The maximum daily dose is 108 mg, with a total maximum dose of 4320 mg over a treatment period of up to 80 weeks. The administration route is subcutaneous, and the frequency of administration is specified in the study protocol. Compliance is monitored through participant diaries and injection logs.
Both formulations of vedolizumab are produced by Takeda Pharma A/S and are not classified as pediatric formulations. The trial does not involve any orphan drug designation. No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in the provided data. The trial aims to evaluate the efficacy of vedolizumab in achieving corticosteroid-free symptomatic, endoscopic, and histological remission in patients with moderately to severely active ulcerative colitis.
Efficacy
The efficacy of the clinical trial titled "VERDICT: In actiVE ulcerative colitis, a RanDomIzed Controlled Trial for determination of the optimal treatment target" will be assessed through a series of primary and secondary endpoints. The primary efficacy evaluation focuses on the time to **ulcerative colitis (UC)**-related complications according to the achieved-target population, defined by the subset of participants who meet their assigned treatment targets. Secondary endpoints include the time to UC-related complications in the full analysis set, including subgroups on and off corticosteroids at the time of achieving other relevant components of the treatment target.
Additional secondary endpoints will assess whether treatment to the target of symptomatic + endoscopic remission is superior to a treatment target of symptomatic remission, and whether treatment to the target of corticosteroid-free symptomatic + endoscopic + histological remission is superior to a treatment target of corticosteroid-free symptomatic + endoscopic remission. The trial will also evaluate changes in fecal calprotectin levels, C-reactive protein (CRP) concentration, UC-100 score, health-related quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment-UC (WPAI-UC) questionnaire at various time points, including Weeks 8, 16, 32, 48, 64, 80, and 96.
Other assessments include changes in the Mayo Clinic Score (MCS) and its subcomponents, Geboes score, Robarts Histopathology Index (RHI) scores, and Nancy Histological Index scores from baseline to specified weeks. The trial will also monitor the number of adverse events (AEs) and serious AEs among the three randomized groups, and evaluate biomarkers and drug concentrations in urine, stool, colonic mucosa, and serum samples. The Symptoms and Impacts Questionnaire for UC (SIQ-UC) tool will be validated in English-fluent subjects. These efficacy parameters will be measured and analyzed at designated intervals throughout the trial duration, which is estimated to conclude by April 30, 2026.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 years.
- Diagnosis of UC confirmed by clinical, endoscopic, and histological evidence prior to screening as per standard criteria.
- Moderately to severely active UC with a Mayo rectal bleeding subscore ≥ 1 and a Mayo endoscopic subscore (MES) ≥ 2, with a minimum disease extent of 15 cm and objective evidence of inflammation that can be visualized using a central endoscopic imaging system.
- Ability of subject to participate fully in all aspects of this clinical trial.
- Written informed consent must be obtained and documented.
- Agree not to participate in an investigation trial for the duration of this trial (observational or other noninterventional trials may be permitted at the discretion of the investigator).
- Negative standard of care tuberculosis (TB) test and hepatitis B and C test prior to randomization unless negative results available from within 12 months prior.
- A male subject who is nonsterilized* and sexually active with a female partner of childbearing potential* agrees to use adequate contraception* from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
- A female subject of childbearing potential* who is sexually active with a nonsterilized* male partner agrees to use routinely adequate contraception* from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
- Up to date with colorectal carcinoma surveillance according to local standards and guidelines. If a subject is not up to date at screening, a standard of care surveillance assessment may be performed during the screening period.
Exclusion Criteria
- Subjects who have historically failed (i.e., had an inadequate response with, lost response to, or were intolerant to) 2 or more compounds or classes of advanced therapeutic options (biologics or small molecules; e.g., anti TNFs, ustekinumab, or tofacitinib) for the treatment of their UC.
- Current or previous treatment with vedolizumab, etrolizumab, or natalizumab.
- Topical therapy (corticosteroid or 5-aminosalicylate) use within 2 weeks prior to screening endoscopy.
- Change to oral corticosteroid therapy dosing within 2 weeks prior to randomization or a corticosteroid dose of >30 mg of prednisone or equivalent at randomization.
- Known diagnosis of Crohn’s disease, indeterminate colitis, ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
- Short gut syndrome.
- Positive stool culture or active Clostridioides difficile infection (as demonstrated by positive toxin and/or antigen).
- Known hepatitis B or C infection; if a negative test result is available in the 12 months prior to randomization, retesting is not required.
- Known active or latent TB; if a negative test result is available in the 12 months prior to randomization, confirmatory testing (per standard of care) is not required before randomization.
- Received any investigational drug within 30 days prior to randomization/target assignment.
- Serious underlying disease other than UC that in the opinion of the investigator may interfere with the subject’s ability to participate fully in the study or would compromise subject safety (such as history of malignancies, major neurological disorders, any unstable or uncontrolled medical disorder).
- History of alcohol or drug abuse that in the opinion of the investigator may interfere with the subject’s ability to comply with the study procedures.
- The subject has active cerebral/meningeal disease, signs/symptoms, or any history of progressive multifocal leukoencephalopathy (PML) prior to randomization.
- Hypersensitivity to any excipient of vedolizumab.
- Active severe infection such as sepsis, cytomegalovirus, listeriosis, or opportunistic infection.
- If female, the subject is pregnant or lactating or intending to become pregnant before, during, or within 18 weeks after the last dose; or intending to donate ova during such time period.
- If male, the subject intends to donate sperm during the course of this study or for 18 weeks after the last dose.
- Vaccination with a live or live-attenuated vaccine within 4 weeks prior to randomization, or planned vaccination during conduct of the study, except vaccination for coronavirus disease of 2019 (COVID 19).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 01 Feb 2021 | 46 |
 France | Not Recruiting | 01 Feb 2021 | 28 |
 Italy | Not Recruiting | 01 Feb 2021 | 58 |
 The Netherlands | Not Recruiting | 01 Feb 2021 | — |
 Poland | Not Recruiting | 01 Feb 2021 | 214 |
| Netherlands | — | — | 45 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Entyvio 108 mg solution for injection in pre-filled syringe | Test | SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE | SUBCUTANEOUS | 108 | 80 | PRD8036142 |
Entyvio 300 mg powder for concentrate for solution for infusion | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS INFUSION | 300 | 96 | PRD1598541 |