Subcutaneous Interval Lengthening of Vedolizumab for Economic Research

NCT ID: NCT06584162

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-09
• Study Completion Date: 2026-02-01

Brief Summary

Rationale: Subcutaneous vedolizumab is an effective maintenance therapy for patients with inflammatory bowel disease. Patients using subcutaneous vedolizumab (every 2 weeks) have higher vedolizumab serum trough concentrations than those who are treated with intravenous vedolizumab (every 4-8 weeks). Since biologic therapies such as vedolizumab are expensive, lengthening of the injection interval (de-escalation) is of interest to reduce health care costs. However, maintaining remission while extending vedolizumab injection intervals has not been evaluated yet but represents a critical component of both medical and societal costs. Studies have suggested that higher vedolizumab serum concentrations are associated with superior clinical outcomes. Our strategy is to administer subcutaneous vedolizumab with prolonged intervals using therapeutic drug monitoring, i.e. dose based on vedolizumab concentrations, to reduce medical and societal costs while preserving remission.

Objectives: To evaluate whether subcutaneous vedolizumab therapeutic drug monitoring (TDM)-guided de-escalation will be cost-effective, compared to normal dosing regimen in patients with inflammatory bowel disease in remission. The secondary objective is to investigate the efficacy of TDM-guided de-escalation subcutaneous vedolizumab dosing compared to standard dosing.

Study design: This is a single-centre, randomized controlled, open-label pilot study.

Study population: 40 patients with inflammatory bowel disease (Crohn's disease or ulcerative colitis) in steroid-free clinical and biochemical remission with subcutaneous vedolizumab maintenance therapy of 108 mg every other week for at least 6 months.

Intervention: Patients will be randomized (1:1) to the 'TDM-guided subcutaneous vedolizumab de-escalation' strategy versus 'standard care' (e.g. continuing standard subcutaneous vedolizumab dosing regimen of 108 mg every other week).

Main study parameters/endpoints: Primary endpoint: cost-effectiveness of the TDM-guided de-escalation group compared to the standard dosing group over 48 weeks. Secondary endpoints include: proportion of patients with sustained clinical remission (based on Harvey-Bradshaw Index or Simple Clinical Colitis Activity Index), proportion of patients with (sustained) biochemical remission (based on c-reactive protein and fecal calprotectin), pharmacokinetic differences (vedolizumab levels and immunogenicity), safety and quality of life (measured by SIBDQ and EQ-5D-5L).

Conditions

Inflammatory Bowel Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

Continuing subcutaneous vedolizumab every other week

Group Type: NO_INTERVENTION

No interventions assigned to this group

Intervention

Therapeutic drug monitoring guided de-escalation

Group Type: EXPERIMENTAL

Vedolizumab Injection

Intervention Type: DRUG

Based on therapeutic drug monitoring, patients could be de-escalated based on a pharmacokinetic model:

Dosing interval Trough Target 20 mg/L

Adjust dosing interval to:

2 weeks < 33 mg/L 2 weeks 2 weeks 33 - 46 mg/L 3 weeks 2 weeks ≥ 46 mg/L 4 weeks 3 weeks < 20 mg/L 2 weeks 3 weeks 20 - 29 mg/L 3 weeks 3 weeks ≥ 29 mg/L 4 weeks 4 weeks < 13 mg/L 2 weeks 4 weeks 13 - 20 mg/L 3 weeks Version number: 6.1, 24-06-2024 22 of 44 4 weeks ≥ 20 mg/L 4 week

Interventions

Vedolizumab Injection

Based on therapeutic drug monitoring, patients could be de-escalated based on a pharmacokinetic model:

Dosing interval Trough Target 20 mg/L

Adjust dosing interval to:

2 weeks < 33 mg/L 2 weeks 2 weeks 33 - 46 mg/L 3 weeks 2 weeks ≥ 46 mg/L 4 weeks 3 weeks < 20 mg/L 2 weeks 3 weeks 20 - 29 mg/L 3 weeks 3 weeks ≥ 29 mg/L 4 weeks 4 weeks < 13 mg/L 2 weeks 4 weeks 13 - 20 mg/L 3 weeks Version number: 6.1, 24-06-2024 22 of 44 4 weeks ≥ 20 mg/L 4 week

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of Crohn's disease or ulcerative colitis
• Clinical and biochemical remission: absence of active inflammatory intestinal symptoms, fecal calprotectin <250 ug/g and CRP <5 mg/g, HBI <5 or SCCAI <4
• Steroid free remission for at least 6 months whilst being treated with subcutaneous vedolizumab at a stable dose of 108mg every other week.

Exclusion Criteria

• Absence of written informed consent;
• Presence of anti-drug antibodies against vedolizumab, these levels will be determined in case the vedolizumab concentration is below 1 ug/ml;
• Concomitant oral glucocorticosteroid usage;
• Imminent need for IBD-related surgery as judged by the treating clinician;
• Actively draining peri-anal fistula;
• Patients with short bowel syndrome, an ostomy or a symptomatic stricture;
• Active participation in another interventional trial;
• Pregnancy or lactation;
• Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness);
• Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

OTHER

Sponsor Role: lead

Responsible Party

Geert D'Haens

Prof. dr. G.R.A.M. D'Haens

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

G.R.A.M. D'Haens, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Locations

Amsterdam UMC

Amsterdam, , Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Suzanne Anjie, MD

Role: CONTACT

s.i.anjie@amsterdamumc.nl

+31655592173

Facility Contacts

Suzanne Anjie, MD

Role: primary

s.i.anjie@amsterdamumc.nl

+31655592173

Other Identifiers

NL80854.018.22

Identifier Type: -

Identifier Source: org_study_id