Crohn DiseasePhase 4LOVE-CDNCT02646683
A Study to Evaluate Efficacy, of Early Versus Late Use of Vedolizumab in Crohn's Disease: the LOVE-CD Study
A Phase 4 study testing vedolizumab in people with Crohn Disease, run by Geert D'Haens at 23 sites in 3 countries.
Trial summary
This multi-centre open label study will involve a minimum of 260 patients in 2 cohorts: 86 patients with 'early CD' defined as disease duration < 24 months and no other treatments than corticosteroids and/or thiopurines and 174 patients with 'late CD' defined as active disease despite treatment with immunosuppressives… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- vedolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 260 participants
- Where
- 23 sitesin 3 countries
- Study dates
- Jul 2015to 26 May 2023
- 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 ileal, ileocolonic or colonic Crohn's disease with histopathological confirmation available in the record of the patient.
- Moderately to severely active CD (CDAI 220-450) with objective evidence of ulcerations visualized on endoscopy.
Show all 12Show fewer
- Anti-TNF discontinued for at least 4 weeks prior to baseline.
- GROUP 1 (EARLY CD):
- Diagnosis of CD < 24 months prior to enrollment
- Demonstrated failure to respond to topical or systemic corticosteroids or intolerance to corticosteroids or: need for > 2 courses of steroids since diagnosis or: steroid dependency at any dose since diagnosis and additionally, but not mandatory, lack of efficacy of thiopurines or intolerance to thiopurines (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 CD)
- Demonstrated failure to respond to at least 3 months of thiopurines or intolerance to thiopurines 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.
Who cannot join
- Previous exposure to any anti-integrin antibodies including- vedolizumab ; α4β7 anti-bodies ; β7 antibodies ; anti- MADCAM-1
- Contraindication for endoscopy.
- History of colonic dysplasia/cancer
- Presence of stoma
- Received other biologics within the last 4 weeks of baseline
- Use of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of enrollment
Show all 13Show fewer
- 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.
- Subjects with known allergy or hyposensitivity to vedolizumab or its components
Trial locations and contacts
23 sites in 3 countries.
23 sites in 3 countries
Belgium15 sites
UZ Antwerpen
Antwerp
Imeldahospital
Bonheiden
AZ Sint-Lucas
Bruges
ULB Erasme
Brussels
Ziekenhuis Oost-Limburg
Genk
AZ Sint Lucas
Ghent
UZ Gent
Ghent
AZ Groeninge
Kortrijk
UZ Leuven
Leuven, 3000
CHC Clinique Saint-Joseph
Liège
CHU de Liège
Liège
ZNA Jan Palfijn
Merksem
AZ Damiaan
Ostend
AZ Delta Roeselare
Roeselare
St Vincentius
Wilrijk
Netherlands5 sites
Academisch Medisch Centrum
Amsterdam
Ziekenhuis Gelderse Vallei
Ede
OLVG
Leiden
Radboud Universitair Medisch Centrum
Nijmegen
Erasmus MC
Rotterdam
Hungary3 sites
Semmelweis University
Budapest
University of Debrecen
Debrecen
Universtiy 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 Crohn's Disease: the LOVE-CD Study (LOw Countries VEdolizumab in CD Study)
This multi-centre open label study will involve a minimum of 260 patients in 2 cohorts: 86 patients with 'early CD' defined as disease duration < 24 months and no other treatments than corticosteroids and/or thiopurines and 174 patients with 'late CD' defined as active disease despite treatment with immunosuppressives and anti-TNF. Patients with 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 (study medication followed by commercial medication once reimbursement is available) and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will ensure that recruitment in either study group is comparable for number and profile of patients (on/off steroids).
Read the detailed description
Crohn's disease (CD) is a chronic inflammatory disease of the small bowel and colon. Symptoms commonly include bloody diarrhea, abdominal pain, weight loss, and fever. There is no known cause or cure for CD. The aim of current CD treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid resections and fistulas.
Treatment options include systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI II, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active CD.
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 ulcerative colitis. The ideal positioning of vedolizumab in the therapeutic armamentarium for CD remains unknown. 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 CD.
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 CD patients with active disease: 1. patients who have been diagnosed < 2 years ago and who only 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.
- Conditions
- Crohn Disease
- Being tested
- vedolizumab
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vedolizumabDrug
Also called Entyvio
| Study group | Role | What they receive |
|---|---|---|
| Early Crohn's disease | Other | VEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50)
week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26 Receives: Drug: vedolizumab |
| Late Crohn's disease | Other | VEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50)
week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26 Receives: Drug: vedolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
The proportion of patients with clinical and endoscopic remission at Week 26
Crohns disease activity index (CDAI) of 150 or lower and Simple endoscopic score for Crohn's disease (SES-CD) < 4.
Measured: week 26
Secondary outcomes (16)
Proportion of patients with endoscopic response at Weeks 26 and 52
SES-CD reduction by ≥ 50 %
Measured: 26 and 52 weeks
Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52
SES-CD reduction
Measured: 26 and 52 weeks
Proportion of patients with clinical response
CDAI decrease of ≥ 70 points from baseline
Measured: 52 weeks
Proportion of patients with clinical remission
(CDAI <=150) at all time other points
Measured: 52 weeks
Proportion of patients with corticosteroid- free clinical remission
(CDAI <=150) at all other time points
Measured: 52 weeks
Proportion of patients with normalized serum C-reactive protein (CRP) at all time points
CRP
Measured: 52 weeks
Proportion of patients with no granulocytes in the biopsies at Weeks 26 and 52.
No granulocytes
Measured: Week 26 and week 52
Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score at Weeks 26 and 52
Geboes score
Measured: Week 26 and week 52
Proportion of patients with sustained clinical response (response at all time points after week 10)
Geboes score reduction
Measured: After week 10
Proportion of patients with sustained clinical remission
(remission at all time points after week 10)
Measured: After week 10
Proportion of patients with draining fistulas
Fistula
Measured: 52 weeks
Proportion of patients that need to be hospitalized
Measured: 52 weeks
Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ)
Questionnaire
Measured: Screening, week 10, week 26 and week 52
Work productivity Index
Questionnaire
Measured: Screening, week 10, week 26 and week 52
Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion
through concentration
Measured: 52 weeks
Quality of life measured by Euroqol (EQ-5D)
Questionnaire
Measured: Screening, week 10, 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 completion26 May 2023
- Study completion26 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies 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
- 260 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
- NCT02646683
- Sponsor's protocol ID
- 2014-100757
- Other IDs
- 2014
- Acronym
- LOVE-CD
- Status last verified
- Jun 2023
- First submitted
- 27 Aug 2015
- Last updated
- 23 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
Publications
Hanzel J, Dreesen E, Vermeire S, Lowenberg M, Hoentjen F, Bossuyt P, Clasquin E, Baert FJ, D'Haens GR, Mathot R. Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study. Inflamm Bowel Dis. 2022 May 4;28(5):689-699. doi: 10.1093/ibd/izab143.
PubMed 34137430
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2023. 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 Crohn's Disease: the LOVE-CD Study (LOw Countries VEdolizumab in CD Study)
- ClinicalTrials.gov ID
- NCT02646683
- Acronym / sponsor ID
- LOVE-CD / 2014-100757
- Conditions
- Crohn Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 260 participants (actual)
- Lead sponsor
- Geert D'HaensUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- Jul 2015 (actual)
- Primary completion
- 26 May 2023 (actual)
- Study completion
- 26 May 2023 (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 260 patients in 2 cohorts: 86 patients with 'early CD' defined as disease duration < 24 months and no other treatments than corticosteroids and/or thiopurines and 174 patients with 'late CD' defined as active disease despite treatment with immunosuppressives and anti-TNF. Patients with 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 (study medication followed by commercial medication once reimbursement is available) and undergo monitoring of endoscopic, histological and clinical disease parameters. No randomization or blinding will be performed but the study management will ensure that recruitment in either study group is comparable for number and profile of patients (on/off steroids).
Detailed description
Crohn's disease (CD) is a chronic inflammatory disease of the small bowel and colon. Symptoms commonly include bloody diarrhea, abdominal pain, weight loss, and fever. There is no known cause or cure for CD. The aim of current CD treatments is to induce and maintain remission, to reduce the need of corticosteroids and avoid resections and fistulas.
Treatment options include systemic and/or topical corticosteroids, purine analogues (6-mercaptopurine and azathioprine), anti-TNF antibodies and surgery. In 2013, results from the GEMINI II, phase 3, randomized controlled trial demonstrated the efficacy of vedolizumab (VDZ) in inducing and maintaining remission in adult patients with active CD.
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 ulcerative colitis. The ideal positioning of vedolizumab in the therapeutic armamentarium for CD remains unknown. 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 CD.
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 CD patients with active disease: 1. patients who have been diagnosed < 2 years ago and who only 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early Crohn's disease | Other | Drug: vedolizumabVEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50) week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26 |
| Late Crohn's disease | Other | Drug: vedolizumabVEDOLIZUMAB 300 mg at week 0,2,6, (10), 14, 22, 30,(34), 38, (42), 46, (50) week 10 = only required for subjects not responding week 34, 42 and 50- only required for subjects who have no endoscopic improvement at week 26 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 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 ileal, ileocolonic or colonic Crohn's disease with histopathological confirmation available in the record of the patient.
Key exclusion criteria (13 listed)
- Previous exposure to any anti-integrin antibodies including- vedolizumab ; α4β7 anti-bodies ; β7 antibodies ; anti- MADCAM-1
- Contraindication for endoscopy.
- History of colonic dysplasia/cancer
- Presence of stoma
- 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 |
|---|---|---|
| vedolizumabAlso: Entyvio | Drug | Early Crohn's disease, Late Crohn's disease |
Primary outcome
The proportion of patients with clinical and endoscopic remission at Week 26
Time frame: week 26
Crohns disease activity index (CDAI) of 150 or lower and Simple endoscopic score for Crohn's disease (SES-CD) < 4.
16 secondary outcomes
Proportion of patients with endoscopic response at Weeks 26 and 52
Time frame: 26 and 52 weeks
Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52
Time frame: 26 and 52 weeks
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) at all time points
Time frame: 52 weeks
Proportion of patients with no granulocytes in the biopsies at Weeks 26 and 52.
Time frame: Week 26 and week 52
Proportion of patients with 25%, 50% and 75% reduction in the Geboes histology score at Weeks 26 and 52
Time frame: Week 26 and week 52
Proportion of patients with sustained clinical response (response at all time points after week 10)
Time frame: After week 10
Proportion of patients with sustained clinical remission
Time frame: After week 10
Proportion of patients with draining fistulas
Time frame: 52 weeks
Proportion of patients that need to be hospitalized
Time frame: 52 weeks
Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ)
Time frame: Screening, week 10, week 26 and week 52
Work productivity Index
Time frame: Screening, week 10, week 26 and week 52
Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion
Time frame: 52 weeks
Quality of life measured by Euroqol (EQ-5D)
Time frame: Screening, week 10, 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 23 Jun 2023.
- Derived from this study: PubMed 34137430Hanzel J, Dreesen E, Vermeire S, Lowenberg M, Hoentjen F, Bossuyt P, Clasquin E, Baert FJ, D'Haens GR, Mathot R. Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study. Inflamm Bowel Dis. 2022 May 4;28(5):689-699. doi: 10.1093/ibd/izab143.
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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)
23 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 in people with Crohn Disease, run by Geert D'Haens at 23 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 12 inclusion and 13 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 23 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 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?
The proportion of patients with clinical and endoscopic remission at Week 26 (time frame: week 26). 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 NCT02646683, which also lists 1 linked publication.
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 Jun 2023.