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Ulcerative ColitisPREDIRESPUCNCT03724929

Value of Pharmacokinetic Assays in the Prediction of Therapeutic Response in Ulcerative Colitis

A study testing Blood sample and Rectosigmoidoscopy in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Saint Etienne at 5 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer α4β7 integrin and which has shown its efficacy in Ulcerative Colitis (UC) by inducing and maintaining clinical response/remission. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ulcerative Colitis
What is being tested?
Blood sample and Rectosigmoidoscopy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
5 sitesFrance
Study dates
4 Mar 2019to 28 Jun 2022
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Aged over 18 years
  • Men or non-pregnant women
  • Patients with a diagnosis of ulcerative colitis who requires to start VDZ
  • Moderate to severe active ulcerative colitis defined as a total mayo score ranging from 6 to 12 and endoscopic Mayo score above 1
  • UC patients with previous failure with TNF antagonist agents and unacceptable side-effects from steroids, and/or immunosuppressive agents (i.e., azathioprine, 6-mercaptopurine, or methotrexate).
  • oral prednisone, are allowed at stable dose for at least 4 weeks-before inclusion. Concomitant immunosuppressive agents, mesalamine, are allowed at stable dose for at least three months before inclusion. Steroid tapering has to be set up at Week 6 after starting VDZ, according to the European Crohn's and Colitis Organisation (ECCO) recommendations.
  • Informed written consent given.

Who cannot join

  • Existing pregnancy, lactation, or intended pregnancy within the next 15 months
  • Minors or History of disease, including mental/emotional disorder that might interfere with their participation in the study
  • Serious secondary illnesses of an acute or chronic nature, which in the opinion of the investigator renders the patient unsuitable for inclusion into the study
  • Inability to comply with the protocol requirements
  • Inability to fill in the diary cards during the last 3 days before each visit
  • Severe Acute UC needed hospitalisation
Show all 17Show fewer
  • Known previous or concurrent malignancy (other than that considered surgically cured, with no evidence for recurrence for 5 years)
  • Short bowel syndrome
  • Previous treatments with vedolizumab, natalizumab, efalizumab or rituximab.
  • Previous treatment with adalimumab within 30 days prior enrollment or infliximab and certolizumab pegol within 60 days before enrollment (This period may be shortened in the opinion of the investigator.)
  • Prior extensive colonic resection, obstructive (symptomatic) intestinal stricture, abdominal abscess, active or latent tuberculosis,
  • Clostridium difficile superinfection;
  • Indeterminate colitis
  • Concomitant leukocyte apheresis.
  • Any contraindication to vedolizumab therapy
  • Patients who denied the protocol, not ability to accept or sign consent of the protocol
  • Subject involved in another interventional clinical trial

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

France5 sites

  • CHU Amiens

    Amiens, 80000

  • CHU Kremlin Bicêtre

    Le Kremlin-Bicêtre, 94270

  • Chu L'Archet

    Nice, 06200

  • Ch Lyon Sud

    Pierre-Bénite, 69230

  • CHU Saint-Etienne

    Saint-Etienne, 42055

Other trials in France

About this study

Official title: Value of Pharmacokinetic Assays (Vedolizumab and Anti-vedolizumab Antibody) in the Prediction of Induction and Maintenance Therapeutic Response in Ulcerative Colitis

Vedolizumab (VDZ) is a monoclonal antibody that binds to the heterodimer α4β7 integrin and which has shown its efficacy in Ulcerative Colitis (UC) by inducing and maintaining clinical response/remission. The French marketing authorization was obtained for Ulcerative Colitis in patients in failure with anti-Tumor Necrosis Factor (anti-TNF) agents. In the pivotal study, correlation between drug levels and clinical response during induction and maintenance therapy were reported. Moreover, in 3.7% of cases, anti-vedolizumab antibodies were reported during the time-course and 1% had samples that were persistently positive. Up to now, data on the pharmacologic VDZ parameters are scarce and the relationships as well as the predictive value of the measurement of VDZ concentrations and VDZ monoclonal antibodies (mAbs) during the induction and maintenance phases remains unknown. It could be of paramount interest to early identify UC patients under VDZ who will be responders to VDZ induction and to identify those who will achieve clinical remission under maintenance therapy with VDZ.

Read the detailed description

The contribution of the pharmacokinetic studies of monoclonal antibodies (anti-TNF antibodies currently) has assumed increasing importance of its use in clinical practice. Therapeutic algorithms for both Infliximab (IFX) and Adalimumab (ADA) have been published and are used by many expert teams in the event of loss of therapeutic response. Similarly, the concentrations are assuming important in the indication of therapeutic de-escalation. Lastly, the assays may predict medium-term therapeutic response to treatment and thus enable proposal of preventive therapeutic changes (5). The Gemini 1 study (phase 3 vedolizumab vs. placebo in Ulcerative Colitis) showed a correlation between drug levels and clinical response during induction and maintenance therapy. Moreover, in 3.7% of cases, anti-vedolizumab antibodies were reported during the time-course and 1% had samples that were persistently positive. (1). In addition, we have decided to assess the clinical response to VDZ induction at W10 (Week 10), as the Gemini III trial for Crohn Disease (Crohn Disease) have reported, among patients who had experienced previous Tumor Necrosis Factor (TNF) antagonist failure, that 15% of those given vedolizumab versus 12% under placebo were in remission at W6 (P=0.433) whereas a higher proportion of them were in remission (26%) under VDZ when compared with the placebo arm (12%) at week 10. Therefore, in clinically non-responders at W10, an additional dose of 300 mg of VDZ will be infused at W10 and every four weeks.

Being tested
Blood sample, Rectosigmoidoscopy
Keywords
Ulcerative Colitis, Vedolizumab, anti-vedolizumab
Medical subject headings
Colitis, Ulcerative

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Blood sampleProcedure or surgery

    Blood samples will be systematically collected at W0, W2, W6, W14 and W52 for vedolizumab pharmacokinetic parameters, including the vedolizumab trough levels and the specific anti-vedolizumab antibody. A supplementary blood sample will be collected at W10 which is the point where a significant greater number of patients were in remission.

  • RectosigmoidoscopyDevice

    Rectosigmoidoscopy will be performed in each center at time points W0, W10 and W52.

Study groups in NCT03724929
Study groupRoleWhat they receive
Ulcerative Colitis patientsExperimentalTo determine if the best cut-off points of vedolizumab (VDZ) trough levels measured at W6 capable to identify UC patients who will achieve a clinical response at week 10 with VDZ and also the best cut-off points of VDZ trough levels measured at W14 capable to identify UC patients who will achieve a clinical remission to maintenance therapy with VDZ : Blood samples will be systematically collected at W0, W2, W6, W14 and W52 for vedolizumab pharmacokinetic parameters, including the vedolizumab trough levels and the specific anti-vedolizumab antibody. A supplementary blood sample will be collected at W10 which is the point where a significant greater number of patients were in remission. Rectosigmoidoscopy will be performed in each center at time points W0, W10 and W52, to evaluate treatment efficacy. In cases of loss of response, rectosigmoidoscopy will be performed before and four weeks after optimization.
Receives: Procedure: Blood sample; Device: Rectosigmoidoscopy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Vedolizumab concentration at week 6

    Determine the optimal threshold of VDZ serum concentration measured at W6 capable to predict the clinical response at week 10 with VDZ.

    Measured: Week 6

Secondary outcomes (9)

  1. Vedolizumab concentration at week 14

    Determine the optimal threshold of VDZ serum concentration measured at W14 capable to predict the clinical response at week 52 with VDZ.

    Measured: Week 14

  2. vedolizumab concentration and anti-vedolizumab antibodies concentrations at week 2

    Investigating whether the pharmacokinetic parameters of vedolizumab (serum trough levels concentrations, specific antibody concentrations) measured at W2 are predictive of a clinical response and clinical remission at W10.

    Measured: Week 2

  3. vedolizumab concentration and anti-vedolizumab antibodies concentrations at week 14

    Investigating whether the pharmacokinetic parameters of vedolizumab (serum trough levels concentrations, specific antibody concentrations) measured at W14 are predictive of a clinical response and clinical remission at W52.

    Measured: Week 14

  4. Vedolizumab concentration at week 6 and mucosal healing

    Analyzing the value of VDZ trough levels measured at W6 to predict mucosal healing at W10 under induction therapy with VDZ in UC

    Measured: Week 6

  5. Vedolizumab concentration at week 14 and mucosal healing

    Analyzing the value of VDZ trough levels measured at W14 to predict mucosal healing at W52 under induction therapy with VDZ in UC

    Measured: Week 14

  6. intra and inter-individual heterogeneity of VDZ levels

    Investigating the intra and inter-individual heterogeneity of VDZ levels within the time-course of VDZ therapy, including the induction and maintenance phases.

    Measured: Week 52

  7. Proportion of loss of clinical response

    Comparing the proportion of loss of clinical response in responder UC patients as well as in primary non-responders requiring VDZ dose-intensification within one-year of follow-up

    Measured: Week 52

  8. Variation of serum VDZ

    Assessing the relationships between the variation of serum VDZ trough levels pre- and post-optimization (delta) and the clinical response in primary non-responder patients requiring additional infusions of VDZ.

    Measured: Week 52

  9. vedolizumab concentration and anti-vedolizumab antibodies concentrations

    Comparing the whole and individual pharmacokinetic parameters (vedolizumab concentration and anti-vedolizumab antibodies concentrations) between patients achieving a clinical remission or not at W52

    Measured: Week 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2018
  2. Study start4 Mar 2019
  3. Primary completion15 Apr 2022
  4. Study completion28 Jun 2022

Why it stopped: The study was stopped due to lack of inclusions

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03724929
Sponsor's protocol ID
1708213
Other IDs
2018-001051-12, 2018
Acronym
PREDIRESPUC
Status last verified
May 2023
First submitted
29 Oct 2018
Last updated
23 May 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A study testing Blood sample and Rectosigmoidoscopy in people with Ulcerative Colitis, run by Centre Hospitalier Universitaire de Saint Etienne at 5 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was stopped early (reason given: The study was stopped due to lack of inclusions). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Vedolizumab concentration at week 6 (time frame: Week 6). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03724929.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.

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