MOdel-Informed Precision Dosing of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease

Official title

MOdel-Informed Precision Dosing (MIPD) of Ustekinumab and VEdolizumab in Inflammatory Bowel Disease - An Independent Randomized Controlled Trial

Overview

The goal of this clinical trial is to investigate if dosage of Ustekinumab (UST) and Vedolizumab (VDZ) based on Model-Informed Precision Dosing (MIPD) is equally as efficient in keeping adults with Inflammatory Bowel Disease (IBD) in remission as management based on what the treating physician deems best. The main question is: Is using pharmacokinetic-pharmacodynamic (PK-PD) models to predict the appropriate dose and dosing interval for VDZ and UST at least as effective as current practices in maintaining IBD remission. As above mentioned the comparison-group is adults with IBD, treated with UST or VDZ, managed as the physician deems best. Participants will: Have blood and stool tests done, as well as answer a questionnaire 4th weekly Have their dosage frequency decided on either by the PK-model or as the physician deems best visit the clinic once every 24 weeks for checkups. Have an endoscopy done at completion of the study (if the disease is primarily located in the small intestine, MRI or capsule endoscopy will be used instead)

Detailed description

Patients will 4th weekly have their drug-concentration in blood measured (and if low, also antidrug antibodies). Hemoglobin, Albumin, CRP and white blood cell count will also be done, as well as a stool-sample for calprotectin measurement.

For the control group however, the clinicians and patients will be blinded for the results of the blood- and stool samples, and the samples for drug concentration will not get analyzed before end of study.

4th weekly they will also answer PRO2 questionnaire, as well as the VAS-F. 8th weekly they will in addition to above mentioned also answer the EQ-5D-5L questionnaire.

At inclusion, after 24 weeks, and at 48 weeks the patients will in addition to the above mentioned also answer the short IBDQ and WPAI questionnaires, as well as be seen in the outpatient clinic to obtain HBI or SCCAI score as applicable, as well as to document any changes in concomitant medication or diseases, and to register if any serious adverse events have presented.

At completion of the trial, patients will have a endoscopy done.

In one subprotocol, the investigators will include 20 patients from Odense to have an endoscopy at both inclusion and completion. Here they will also have biopsies taken from all segments of the colon, which will be stores in a biobank for future research.

In another subprotocol 20 patients will be included to have a intestinal ultrasound done at inclusion and completion.

In a biobank for future research the investigators will also store serum-samples, buffy coat, and stool samples collected at inclusion, after 24 and 48 weeks from all included patients.

Interventions

• Drug PK-model to decide when to dose Vedolizumab and Ustekinumab
  the pharmacokinetic model will include information about inflammatory parameters both in blood- and fecal samples, as well as weight, sex, previous treatments and drug concentration.

Primary outcome measures

• The fraction of patients in steroid-free remission [Time frame: at the end of the observation period (48 weeks)]

Secondary outcome measures (12)

• The fraction of the observation period (48 weeks) where the disease is in steroid-free remission [Time frame: this is registered every 4th week throughout the study duration of 48 weeks.]
• The financial costs associated with the two treatment strategies over the observation period (12 months) [Time frame: through study completion, an average of 48 weeks]
• Endoscopic healing of the mucosa [Time frame: at completion of study, approximately 48 weeks]
• Changes in quality of life during the study period [Time frame: 48 weeks]
• Quality of life as QALYs [Time frame: 48 weeks]
• Clinical Disease Activity [Time frame: 48 weeks]
• Inflammatory burden over the observational period [Time frame: 48 weeks]
• Expenses for analysis of drug concentration [Time frame: 48 weeks]
• Expenses for drugs [Time frame: 48 weeks]
• Drug persistency [Time frame: 48 weeks]
• Disease flares [Time frame: 48 weeks]
• Fatigue [Time frame: 48 weeks.]

Eligibility criteria

Inclusion criteria

• Ulcerative colitis or Crohn's disease. Diagnosed, according to universally acknowledged criteria, a minimum of 3 months prior to inclusion
• Age ≥ 18
• Stable treatment with VDZ or UST for at least 3 months prior to inclusion
• Stable disease activity, mild activity is accepted, defined by fecal calprotectin ≤ 200, and a weighted PRO2 < 14 for CD or a PRO2 ≤3 for UC
• No change in medical therapy within 3 months prior to inclusion, as concomitant therapy with other immune suppressants is allowed (Azathioprine, 6-mercaptopurine, Methotrexate, 5-aminosalicylic acid)
• The patient must be able to understand patient information material
• The patient must be able to give informed written consent

Exclusion criteria

• Having a diagnose of indeterminate colitis
• Having a stoma or pouch
• Fistulizing disease being the primary reason for treatment with VDZ or UST
• Expected eminent change of therapy
• Expected need for surgical intervention within the coming 3 months
• Contraindication against continuing treatment with VDZ or UST, including prior acute or delayed infusion reaction to VDZ or UST
• Any active infection requiring parenteral treatment, known infection with tuberculosis, human immunodeficiency virus (HIV) or hepatitis virus.
• Any condition which the responsible physician finds incompatible with participation in the study
• Patients unable to participate in the collection of symptoms scores
• Patients who are pregnant or nursing at time of inclusion

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Denmark · 6 centers

• Dept. of Gastrointestinal Diseases — Aalborg
• Dept. of Internal Medicin — Esbjerg
• Dept. of Gastrointestinal Diseases — Hvidovre
• Dept. of medicine — Nyborg
• Dept. of Gastrointestinal Diseases — Odense
• Dept. of Medicine — Vejle

Publications

• Frimor C, Steenholdt C, Widigson ESK, Kjeldsen J, Larsen L, Burisch J, Joergensen MT, Halling ML, Kloft C, Ainsworth MA. MOdel-informed precision dosing (MIPD) of ustekinumab and VEdolizumab in inflammatory bowel disease: protocol for an Independent randomised, controlled, multicentre Trial (MOVE-IT). BMJ Open Gastroenterol. 2025 Dec 25;12(1):e001985. doi: 10.1136/bmjgast-2025-001985. PMID 41453773

Identifiers

NCT: NCT06788340 · 32844 · 2024-517123-39-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗