Study of Relationship Between Vedolizumab Therapeutic Drug Monitoring, Biomarkers of Inflammation and Clinical Outcomes

Completed

• Conditions: Crohn Disease; Inflammatory Bowel Diseases; Colitis, Ulcerative
• Interventions: Other: No Intervention

• Registration Number: NCT04567628
• Lead Sponsor: Takeda

Brief Summary

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).

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 Timeline

• Study First Submitted: 2020-09-23
• Study First Submitted QC: 2020-09-23
• Study First Posted: 2020-09-28
• Study Start: 2020-10-05
• Primary Completion: 2021-09-22
• Study Completion: 2021-09-22
• Results First Submitted: 2022-09-22
• Status Verified: 2023-09
• Results First Submitted QC: 2023-09-05
• Last Update Submitted: 2023-09-05
• Results First Posted: 2024-03-15
• Last Update Posted: 2024-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7873

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.

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Exclusion Criteria

No exclusion criteria will be applied.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Historical Cohort	No Intervention	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.
TDM Cohort	No Intervention	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.

Primary Outcome Measures

Name	Time	Method
TDM Cohort: Correlation Between Week 6 Vedolizumab TDM and Week 30 Faecal Calprotectin (FCP)	After the first dose of vedolizumab (at Week 30)	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.

Secondary Outcome Measures

Name	Time	Method
TDM Cohort: C-reactive Protein (CRP) Level at Week 30	After the first dose of vedolizumab (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.
Number of Participants Categorized Based on Dose Escalation	Baseline (Week 0) up to Week 30 (after first dose of vedolizumab)	Dose escalation was defined as a change from doses every 8 weeks to every 4 weeks.
TDM Cohort: Disease Score for Crohn's Disease (CD) Participants Based on Harvey-Bradshaw Index (HBI) at Week 30	After the first dose of vedolizumab (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.
TDM Cohort: Disease Score for Ulcerative Colitis (UC) Participants Based on Partial Mayo Score at Week 30	After the first dose of vedolizumab (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.
TDM Cohort: Number of Participants Categorized Based on Treatment Persistence at the End of the TDM Study at Week 30	After the first dose of vedolizumab (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.
Treatment Duration	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)	Treatment duration was defined as the length of time a participant remains on treatment (i.e., from the year 2015 to 2020).

Trial Locations

Locations (1)

Takeda Canada; 🇨🇦 Toronto, Ontario, Canada