A Study to Evaluate Efficacy, of Early Versus Late Use of Vedolizumab in Crohn's Disease: the LOVE-CD Study (LOVE-CD)

Purpose of this study?

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.

Inclusion Criteria:

• 18 Years to 80 Years
• In the opinion of the investigator, the Patient is capable of understanding and complying with protocol requirements.
• The Patient signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• 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.
• 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.

Exclusion Criteria:

1. Previous exposure to any anti-integrin antibodies including- vedolizumab ; α4β7 anti-bodies ; β7 antibodies ; anti- MADCAM-1
2. Contraindication for endoscopy.
3. History of colonic dysplasia/cancer
4. Presence of stoma
5. Received other biologics within the last 4 weeks of baseline
6. Use of 5-aminosalicylic acid (5-ASA) or corticosteroid enemas/suppositories within 2 weeks of enrollment
7. Chronic hepatitis B or C infection
8. Evidence of or treatment for C. difficile infection or other intestinal pathogen at screening within 4 weeks prior to enrollment
9. Active or latent tuberculosis
10. Conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedures.
11. Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer.
12. Positive progressive multifocal leukoencephalopathy ( PML) subjective symptom checklist before enrollment.
13. Subjects with known allergy or hyposensitivity to vedolizumab or its components

Primary outcome measures:

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.

Secondary outcome measures:

1.    Proportion of patients with endoscopic response at Weeks 26 and 52 [ Time Frame: 26 and 52 weeks ]

SES-CD reduction by ≥ 50 %

2.    Proportion of patients with 25% and 75% reduction of SES-CD at Weeks 26 and 52 [Time Frame: 26 and 52 weeks ]

SES-CD reduction

3.    Proportion of patients with clinical response [ Time Frame: 52 weeks ]

CDAI decrease of ≥ 70 points from baseline

4.    Proportion of patients with clinical remission [ Time Frame: 52 weeks ]

(CDAI <=150) at all time other points

5.    Proportion of patients with corticosteroid- free clinical remission [ Time Frame: 52 weeks]

(CDAI <=150) at all other time points

6.    Proportion of patients with normalized serum C-reactive protein (CRP) at all time points

[ Time Frame: 52 weeks ]

CRP

7.    Proportion of patients with no granulocytes in the biopsies at Weeks 26 and 52. [ Time Frame: Week 26 and week 52 ]

No granulocytes

8.    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 ]

Geboes score

9.    Proportion of patients with sustained clinical response (response at all time points after week 10) [ Time Frame: After week 10 ]

Geboes score reduction

10. Proportion of patients with sustained clinical remission [ Time Frame: After week 10 ] (remission at all time points after week 10)

11. Proportion of patients with draining fistulas [ Time Frame: 52 weeks ]

Fistula

12. Proportion of patients that need to be hospitalized [ Time Frame: 52 weeks ]

13. Quality of life measured by Inflammatory Bowel Disease Questionnaire ( IBDQ) [ Time Frame: Screening, week 10, week 26 and week 52 ]

Questionnaire

14. Work productivity Index [ Time Frame: Screening, week 10, week 26 and week 52 ]

Questionnaire

15. Serum concentrations of vedolizumab and antibodies to vedolizumab before every infusion [ Time Frame: 52 weeks ]

through concentration

16. Quality of life measured by Euroqol (EQ-5D) [ Time Frame: Screening, week 10, week 26 and week 52 ]

Questionnaire

Study Locations in Europe:

Belgium, Hungary, Netherlands

Estimated Study Completion Date: December 2023

Further information on clinicaltrial.gov with trial number NCT02646683