Clinical trial NCT06788340: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Inflammatory Bowel Diseases
Crohn Disease
Ulcerative Colitis
Keywords: MIPD
Model-Informed Precision Dosing
Therapeutic Drug Monitoring
TDM
Inflammatory Bowel Disease
Crohn's disease
Ulcerative colitis
Biologic therapy
Ustekinumab
Vedolizumab
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
First posted: 2025-01-23
Enrollment: 166
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: The fraction of patients in steroid-free remission
timeFrame: at the end of the observation period (48 weeks)
Secondary outcomes:
measure: The fraction of the observation period (48 weeks) where the disease is in steroid-free remission
timeFrame: this is registered every 4th week throughout the study duration of 48 weeks.
measure: The financial costs associated with the two treatment strategies over the observation period (12 months)
timeFrame: through study completion, an average of 48 weeks
measure: Endoscopic healing of the mucosa
timeFrame: at completion of study, approximately 48 weeks
measure: Changes in quality of life during the study period
timeFrame: 48 weeks
measure: Quality of life as QALYs
timeFrame: 48 weeks
measure: Clinical Disease Activity
timeFrame: 48 weeks
measure: Inflammatory burden over the observational period
timeFrame: 48 weeks
measure: Expenses for analysis of drug concentration
timeFrame: 48 weeks
measure: Expenses for drugs
timeFrame: 48 weeks
measure: Drug persistency
timeFrame: 48 weeks
measure: Disease flares
timeFrame: 48 weeks
measure: Fatigue
timeFrame: 48 weeks.
measure: Disease impact on work productivity and performance of daily activities
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Dept. of Gastrointestinal Diseases
city: Esbjerg
country: Denmark
facility: Dept. of Internal Medicin
city: Hvidovre
country: Denmark
facility: Dept. of Gastrointestinal Diseases
city: Nyborg
country: Denmark
facility: Dept. of medicine
city: Odense
country: Denmark
facility: Dept. of Gastrointestinal Diseases
city: Vejle
country: Denmark
facility: Dept. of Medicine
Study officials:
affiliation: Odense University Hospital
name: Mark A Ainsworth, professor, DMSc
role: PRINCIPAL_INVESTIGATOR
References: