Colitis, UlcerativePhase 4LOVE-UCNCT02646657
An Open Label Phase 4 Study to Evaluate Efficacy of Early Versus Late Use of Vedolizumab in Ulcerative Colitis
A Phase 4 study testing Vedolizumab 300 mg in people with Colitis, Ulcerative, run by Geert D'Haens at 20 sites in 3 countries.
Trial summary
This multi-centre open label study will involve a minimum of 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Colitis, Ulcerative
- What is being tested?
- Vedolizumab 300 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 20 sitesin 3 countries
- Study dates
- Jul 2015to Aug 2020
- Phase
- Phase 4
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
- The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Age 18 to 80
- Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
- Established diagnosis of ulcerative colitis with histopathological confirmation available in the record of the patient.
- Moderate to severe active UC (total Mayo score > 6) with objective evidence of inflammation that can be visualized on endoscopy. All endoscopies will be video-taped for later review, rereading and quality assurance. Patients must have an endoscopic Mayo score of 2 or 3.
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- Anti-TNF discontinued for at least 6 weeks
- Written informed consent must be obtained and documented
- GROUP 1 (EARLY UC)
- Diagnosis of UC < 4 years prior to enrollment confirmed by clinical, endoscopic and histopathological evidence.
- Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to topical or systemic corticosteroids or intolerance to corticosteroids or: need for > 1 course of steroids per year or: steroid dependency at any dose and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (azathioprine, 6-mercaptopurine or 6-thioguanine) (any duration). Patients who are using thiopurines at screening must have used them for > 3 months (last 4 weeks at stable dose).
- GROUP 2 (LATE UC)
- Diagnosis of UC confirmed by clinical, endoscopic and histopathological evidence.
- Demonstrated failure to respond to aminosalicylates or intolerance to aminosalicylates and: failure to respond to at least 3 months of thiopurines (TP) or intolerance to TP and: failure to respond to at least 1 anti-TNF or intolerance to anti-TNF or loss of response to at least 1 anti-TNF. Loss of response to anti-TNF is defined as recurrence of symptoms during maintenance dosing following prior clinical benefit.
- May continue stable dose of conventional therapies for Inflammatory Bowel Disease ( IBD) including aminosalicylates and thiopurines and corticosteroids. Steroids will be tapered by protocol by week 14. Anti-TNF must be discontinued for > 6 weeks.
Who cannot join
- Prior treatment with vedolizumab.
- Contraindication for endoscopy.
- History of colonic dysplasia/cancer
- Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining
- Received other biologics within the last 4 weeks of baseline
- Use of 5-ASA or corticosteroid enemas/suppositories within 2 weeks of enrollment
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- Chronic hepatitis B or C infection
- Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment
- Active or latent tuberculosis
- Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
- Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
- Positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist before enrollment
Trial locations and contacts
20 sites in 3 countries.
20 sites in 3 countries
Belgium12 sites
Imeldahospital
Bonheiden
ULB Erasme
Brussels
Ziekenhuis Oost-Limburg
Genk
AZ Sint-Lucas
Ghent
UZ Gent
Ghent
AZ Groeninge
Kortrijk
Leuven AcademicHospital
Leuven
CHC Clinique Saint-Joseph
Liège
CHU Liege
Liège
ZNA Jan Palfijn
Merksem
AZ Damiaan
Ostend
AZ Delta- Roeselare
Roeselare
Netherlands5 sites
Academic Medical Center
Amsterdam
OLVG
Amsterdam
Ziekenhuis Gelderse Vallei
Ede
Radboud UMC
Nijmegen
Erasmus MC
Rotterdam
Hungary3 sites
Semmelweis University
Budapest
University of Debrechen
Debrecen
University of Szeged
Szeged
About this study
Official title: An Open Label Interventional Phase 4 Study to Evaluate Efficacy, Safety and Mucosal Healing of Early Versus Late Use of Vedolizumab in Ulcerative Colitis: the LOVE-UC Study (LOw Countries VEdolizumab in UC Study)
This multi-centre open label study will involve a minimum of 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. Participants will be treated with 12 months of open label vedolizumab and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will make sure recruitment in either study group is comparable for number and profile of patients (extent of disease and on/off corticosteroids).
Read the detailed description
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Symptoms include bloody diarrhea, weight loss, and fever. There is no known cause or cure for UC. The aim of current UC treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid colectomy.
Treatment options include 5-Aminosalicylates (5-ASA), systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI I, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active UC.
VDZ (MLN0002 or MLN02), inhibits the interaction between α4β7 integrin on memory T and B cells and mucosal addressin cell adhesion molecule-1 expressed on the vascular endothelium of the gut and has been shown to be effective in both inducing and maintaining clinical remission in UC.
With other (anti-TNF) biologics, outcomes have usually been better if the treatment was started earlier in the disease course and if the patients had not been exposed to prior antibody treatments. Therefore, it appears appropriate and desirable to test the potency of vedolizumab in an earlier phase of UC. Indeed, also with vedolizumab patients previously exposed to biologics appear to have lower success rates with vedolizumab, so a position earlier in the disease course would most likely lead to better outcomes.
This is an investigator-initiated open label study of VDZ therapy in 2 distinct populations of UC patients with active disease: 1. patients who have been diagnosed < 4 years ago and who only have been exposed to aminosalicylates and corticosteroids and 2. patients who have been exposed to immunomodulators and/or anti-TNF agents in addition to steroids and aminosalicylates.
VDZ has been shown to be efficacious at inducing and maintaining remission in UC. However, data about the endoscopic and histological effects of VDZ in 'early UC' are lacking. Therefore, the investigators propose to perform an interventional study in early and late UC patients including endoscopic and histological assessment
- Conditions
- Colitis, Ulcerative
- Being tested
- Vedolizumab 300 mg
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vedolizumab 300 mgDrug
Also called Entyvio
Open-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46
| Study group | Role | What they receive |
|---|---|---|
| Early UC | Other | Patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids Receives: Drug: Vedolizumab 300 mg |
| Late UC | Other | Patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. Receives: Drug: Vedolizumab 300 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical and endoscopic remission
Defined as a Mayo Clinic score ≤2 and no subscore >1
Measured: Change in Mayo score from baseline to week 26
Secondary outcomes (13)
Proportion of patients with endoscopic response
Change in endoscopic Mayo score of 1 or more than 1
Measured: Week 26 and week 52
Proportion of patients with clinical response
Mayo score < 6
Measured: 52 weeks
Proportion of patients with clinical remission
Mayo Clinic score ≤2 and no subscore >1
Measured: 52 weeks
Proportion of patients with corticosteroid- free clinical remission
Mayo remission score ≤2 and no subscore >1
Measured: 52 weeks
Proportion of patients with normalized serum C-reactive protein (CRP)
Normal CRP
Measured: 52 weeks
Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score
Geboes score reduction
Measured: At week 26 and week 52
Proportion of patients with sustained clinical response
A Mayo score < 6
Measured: After week 10.
Proportion of patients with sustained clinical remission
Mayo Clinic score ≤2 and no subscore >1.
Measured: After week 10.
Proportion of patients that need to be hospitalized
hospitalization
Measured: 52 weeks
Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ )
Questionnaire
Measured: At enrollment, week 26 and week 52
Work productivity Index
Questionnaire
Measured: At enrollment, week 26 and week 52
Serum concentrations of vedolizumab and antibodies to vedolizumab
through concentration
Measured: Before every infusion
Quality of life measured by and Euroquol
Questionnaire
Measured: At enrollment, week 26 and week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2016 (estimated)
- Study startJul 2015
- Primary completionAug 2020
- Study completionAug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colitis, UlcerativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Geert D'Haens
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Sponsor-investigator, Geert D'Haens, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Geert D'Haens, Prof., Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02646657
- Sponsor's protocol ID
- 2014-100756
- Other IDs
- 2014
- Acronym
- LOVE-UC
- Status last verified
- Oct 2020
- First submitted
- 27 Aug 2015
- Last updated
- 8 Oct 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Interventional Phase 4 Study to Evaluate Efficacy, Safety and Mucosal Healing of Early Versus Late Use of Vedolizumab in Ulcerative Colitis: the LOVE-UC Study (LOw Countries VEdolizumab in UC Study)
- ClinicalTrials.gov ID
- NCT02646657
- Acronym / sponsor ID
- LOVE-UC / 2014-100756
- Conditions
- Colitis, Ulcerative
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Geert D'HaensUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Jul 2015
- Primary completion
- Aug 2020 (actual)
- Study completion
- Aug 2020 (actual)
- First posted
- 6 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multi-centre open label study will involve a minimum of 120 patients in 2 cohorts: 60 patients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids and 60 patients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. Participants will be treated with 12 months of open label vedolizumab and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will make sure recruitment in either study group is comparable for number and profile of patients (extent of disease and on/off corticosteroids).
Detailed description
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. Symptoms include bloody diarrhea, weight loss, and fever. There is no known cause or cure for UC. The aim of current UC treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid colectomy.
Treatment options include 5-Aminosalicylates (5-ASA), systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI I, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active UC.
VDZ (MLN0002 or MLN02), inhibits the interaction between α4β7 integrin on memory T and B cells and mucosal addressin cell adhesion molecule-1 expressed on the vascular endothelium of the gut and has been shown to be effective in both inducing and maintaining clinical remission in UC.
With other (anti-TNF) biologics, outcomes have usually been better if the treatment was started earlier in the disease course and if the patients had not been exposed to prior antibody treatments. Therefore, it appears appropriate and desirable to test the potency of vedolizumab in an earlier phase of UC. Indeed, also with vedolizumab patients previously exposed to biologics appear to have lower success rates with vedolizumab, so a position earlier in the disease course would most likely lead to better outcomes.
This is an investigator-initiated open label study of VDZ therapy in 2 distinct populations of UC patients with active disease: 1. patients who have been diagnosed < 4 years ago and who only have been exposed to aminosalicylates and corticosteroids and 2. patients who have been exposed to immunomodulators and/or anti-TNF agents in addition to steroids and aminosalicylates.
VDZ has been shown to be efficacious at inducing and maintaining remission in UC. However, data about the endoscopic and histological effects of VDZ in 'early UC' are lacking. Therefore, the investigators propose to perform an interventional study in early and late UC patients including endoscopic and histological assessment
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early UC | Other | Drug: Vedolizumab 300 mgPatients with 'early UC' defined as disease duration < 4 years and no other treatments than aminosalicylates and/or corticosteroids |
| Late UC | Other | Drug: Vedolizumab 300 mgPatients with 'late UC' defined as active disease despite treatment with immunosuppressives (IS) and/or anti-TNF. Patients wih intolerance to IS AND anti-TNF will also be allowed in the latter group. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- In the opinion of the investigator, the subject is capable of understanding and complying with protocol requirements.
- The subject signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
- Age 18 to 80
- Male or non-pregnant, non-lactating females. Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records (i.e., tubal ligation, hysterectomy, or post-menopausal [defined as a minimum of one year since the last menstrual period]).
- Established diagnosis of ulcerative colitis with histopathological confirmation available in the record of the patient.
Key exclusion criteria (12 listed)
- Prior treatment with vedolizumab.
- Contraindication for endoscopy.
- History of colonic dysplasia/cancer
- Extensive colonic resection, i.e. subtotal or total colectomy with <15 cm colon remaining
- Received other biologics within the last 4 weeks of baseline
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vedolizumab 300 mgAlso: EntyvioOpen-label VEDOLIZUMAB 300 mg at week 0,2,6, 14, 22, 30, 38, 46 | Drug | Early UC, Late UC |
Primary outcome
Clinical and endoscopic remission
Time frame: Change in Mayo score from baseline to week 26
Defined as a Mayo Clinic score ≤2 and no subscore >1
13 secondary outcomes
Proportion of patients with endoscopic response
Time frame: Week 26 and week 52
Proportion of patients with clinical response
Time frame: 52 weeks
Proportion of patients with clinical remission
Time frame: 52 weeks
Proportion of patients with corticosteroid- free clinical remission
Time frame: 52 weeks
Proportion of patients with normalized serum C-reactive protein (CRP)
Time frame: 52 weeks
Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score
Time frame: At week 26 and week 52
Proportion of patients with sustained clinical response
Time frame: After week 10.
Proportion of patients with sustained clinical remission
Time frame: After week 10.
Proportion of patients that need to be hospitalized
Time frame: 52 weeks
Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ )
Time frame: At enrollment, week 26 and week 52
Work productivity Index
Time frame: At enrollment, week 26 and week 52
Serum concentrations of vedolizumab and antibodies to vedolizumab
Time frame: Before every infusion
Quality of life measured by and Euroquol
Time frame: At enrollment, week 26 and week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geert D'Haens, Prof. principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
20 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Vedolizumab 300 mg in people with Colitis, Ulcerative, run by Geert D'Haens at 20 sites in 3 countries.
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 15 inclusion and 12 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: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Belgium, Netherlands, Hungary. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical and endoscopic remission (time frame: Change in Mayo score from baseline to week 26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Oct 2020; AzTrials last refreshed its copy on 27 Oct 2026.