Study of Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes (VEDO TDM RWE)

The Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes in the Real World Setting (VEDO TDM RWE)

The purpose of this study is to determine if a relationship exists between Week 6 vedolizumab therapeutic drug monitoring (TDM) and Week 30 Faecal calprotectin (FCP).

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative
• Intervention / Treatment: Other: No Intervention

Detailed Description

This is a non-interventional, retrospective, and longitudinal study of participants with IBD (UC or CD) receiving vedolizumab between years 2015 and 2020. The study will determine the real-world evidence of vedolizumab, its relationship with TDM, biomarkers of inflammation, and its effect on clinical outcomes in a real-world setting.

This study will enroll approximately 5,500 participants. Participants will be enrolled in 2 cohorts: TDM Cohort and Historical Cohort. The study will have a retrospective data collection of the participants from PSP between the years 2015 and 2020. The study will include longitudinal analysis of data collected in a subset of Takeda Canada PSP, specifically for those participants on vedolizumab, some of which received biomarker testing and TDM at pre-specified intervals during their treatment.

This multi-center trial will be conducted in Canada. The overall time for data collection in the study will be approximately 5 years.

• Study Type: Observational
• Enrollment (Actual): 7873

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, ON M5H 4E3
      • Takeda Canada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participants with IBD (UC or CD) receiving vedolizumab between years 2015 and 2020.

Description

Inclusion Criteria:

1. The participant or, when applicable, the participant's legally acceptable representative signed and dated a written, informed consent form, which specified secondary use of their data, and any required privacy authorization as part of their enrollment in Takeda Canada's PSP.
2. Received or receiving vedolizumab between the years 2015 and 2020.

Exclusion Criteria:

No exclusion criteria will be applied.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
TDM Cohort; Participants diagnosed with inflammatory bowel disease (IBD) (UC or CD) within Takeda Canada Patient Support Program (PSP) group who received treatment with vedolizumab 300 milligram (mg), infusion, intravenously, at Weeks 0, 2, and 6, and every 8 weeks thereafter as per product Health Canada Product Monograph, or every 4 or 6 weeks thereafter as per standard clinical practice between the year 2015 to 2020 along with the biomarker testing and TDM at pre-specified intervals during their treatment were observed retrospectively.	Other: No Intervention; As this was an observational study, no intervention was administered.
Historical Cohort; Participants diagnosed with IBD (UC or CD) within Takeda Canada PSP group who received treatment with vedolizumab 300 mg, infusion, intravenously, at Weeks 0, 2, and 6, and every 8 weeks thereafter as per product Health Canada Product Monograph, or every 4 or 6 weeks thereafter as per standard clinical practice between the year 2015 to 2020 but did not undergo biomarker testing or TDM during their treatment were observed retrospectively.	Other: No Intervention; As this was an observational study, no intervention was administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP)	The relationship between vedolizumab TDM at Week 6 and FCP levels at Week 30 were studied using univariate and multivariate logistic regression models. Multivariate analyses were performed to control for possible confounding factors such as age, sex, disease type (CD/UC), duration, prior immunomodulator/biologic therapy, vedolizumab start and end dates, vedolizumab dose, vedolizumab frequency, and albumin. FCP was used as a surrogate marker for disease severity, and by extension drug efficacy. The FCP level was detected in participant's stool 30 weeks after the participant's first dose of vedolizumab. FCP was treated as a continuous variable for correlation analysis to determine Spearman's correlation coefficient. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort.	After the first dose of vedolizumab (at Week 30)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TDM Cohort: C-reactive Protein (CRP) Level at Week 30	The CRP level were detected in participant's blood 30 weeks after the participant's first dose of vedolizumab. CRP was used as a surrogate marker for disease severity, and by extension drug efficacy. This outcome measure was planned to be analyzed separately in participants with UC and CD who were collectively a part of the TDM Cohort.	After the first dose of vedolizumab (at Week 30)
TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-Bradshaw Index (HBI) at Week 30	Disease activity scores of CD participants were based on HBI. It consists of clinical parameters: general well-being (0 = very well to 4 = terrible), abdominal pain (0 = none to 3 = severe), number of liquid or soft stools per day, abdominal mass (0 = none to 3 = definite and tender), and complications (8 items; 1 score per item). The total score is sum of sub scores, where score <5 = remission, 5 to 7 = mild disease activity, 8 to 16 = moderate disease activity and >16 = severe disease activity. This outcome measure was planned to be analyzed only in participants with CD.	After the first dose of vedolizumab (at Week 30)
TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30	Disease activity scores of UC participants were based on Partial Mayo score. It consists of 3 sub-scores: stool pattern, most severe rectal bleeding of the day, and global assessment by physician, each graded from 0 to 3 with higher scores indicating more severe disease. These scores are summed to give a total score range of 0 to 9. Here, higher scores indicate more severe disease. This outcome measure was planned to be analyzed only in participants with UC.	After the first dose of vedolizumab (at Week 30)
Number of Participants Categorized Based on Dose Escalation	Dose escalation was defined as a change from doses every 8 weeks to every 4 weeks.	Baseline (Week 0) up to Week 30 (after first dose of vedolizumab)
TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30	Treatment persistence was defined as whether the participant was still on the treatment at the end of the TDM study. This outcome measure was planned to be analyzed only in participants enrolled in the TDM Cohort.	After the first dose of vedolizumab (at Week 30)
Treatment Duration	Treatment duration was defined as the length of time a participant remains on treatment (i.e., from the year 2015 to 2020).	From treatment initiation up to discontinuation of treatment or up to data extraction date Oct 2020), whichever occurs first (maximum up to approximately 5 years)

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Study record dates

Study Major Dates

• Study Start (Actual): October 5, 2020
• Primary Completion (Actual): September 22, 2021
• Study Completion (Actual): September 22, 2021

Study Registration Dates

• First Submitted: September 23, 2020
• First Submitted That Met QC Criteria: September 23, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Colitis; Inflammation; Inflammatory Bowel Diseases; Crohn Disease; Colitis, Ulcerative
• Other Study ID Numbers: Vedolizumab-5062; U1111-1256-3663 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No