Effectiveness of Vedolizumab in CD Patients Naïve to Anti-TNF

Effectiveness of Vedolizumab Therapy in Inducing Clinical Remission in CD Patients Naïve to Anti-TNF and Its Capability to Halt Disease Progression

Anti-cytokine antibodies, such as Infliximab (an anti TNF alfa chimeric antibody) and Adalimumab (an anti TNF alfa humanize antibody), have been developed and used in clinical practice for the treatment of patients with Crohn disease (CD). Unfortunately, their efficacy is limited. Based on these concepts, a new drug has been developed for IBD treatment. Vedolizumab (VDZ) is able to recognize the α4β7 heterodimer, and selectively blocks gut lymphocyte trafficking.

The hypothesis of this study is that VDZ therapy may be to halt CD disease progression during time and modifying its natural history, using Lemann Index.

Study Overview

• Status: Withdrawn
• Conditions: Crohn Disease
• Intervention / Treatment: Drug: vedolizumab

Detailed Description

All patients who will enter in the study will be follow-up at weeks 2-6-14-22-30-38-46 or before in case of relapse. A relapse will be defined by an Harvey Bradshaw Index ≥ 5 for 2 consecutive weeks. The following data are to be recorded:

1. Physical examination
2. Adverse Event Review
3. Weight in Kg
4. Full blood count
5. Biochemical series including serum iron, serum ferritin, C reactive protein (PCR), ESR (eritrosedimatation rate)
6. Fecal Calprotectin
7. VDZ fecal loos
8. VDZ trough levels and antidrug antibodies
9. Current treatments

The last visit will be performed at week 54. The following data are to be recorded:

1. Physical examination
2. Adverse Event Review
3. Weight in Kg
4. Full blood count
5. Biochemical series including serum iron, serum ferritin, C reactive protein (PCR), ESR (eritrosedimatation rate)
6. Fecal Calprotectin
7. VDZ fecal loos
8. VDZ trough levels and antidrug antibodies
9. Current treatments
10. Routine lower and upper gastrointestinal endoscopy and magnetic resonance imaging or computed tomography of the small bowel
11. SES-CD
12. Lemann Index

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have given written informed consent to participate
• Be aged between 18 and 80
• Have a moderate/severe CD defined by an HBI >7 CD

Exclusion Criteria:

• previous treatment with anti-TNF drugs,
• concomitant use of immune-modulator drugs for CD (azathioprine/6-mercaptopurine, methotrexate)
• ulcerative colitis (UC) or inflammatory bowel disease undetermined (IBD-U) diagnosis
• symptomatic obstructive disease
• bowel resection within the past 6 months
• ileostomy
• extensive small bowel resection (as determined by the investigator) or a short bowel syndrome
• patients who are currently receiving total parenteral nutrition
• history of cancer in the past 5 years
• pregnancy known at the study inclusion
• positive Clostridium difficile stool assay
• Listeria, human immunodeficiency virus, central nervous system demyelinating disease, untreated tuberculosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: single arm study; Vedolizumab 300 mg iv at week 0, week 2 and week 6, than every 8 weeks.	Drug: vedolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Harvey Bradshaw index	Primary responders will defined as by a decrease of Harvey Bradshaw Index at week 14 of 3 point from the Harvey Bradshaw Index calculate at week 0.	Week 0-14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lèmann Index		Week 0 and Week 54
VDZ trough levels		Week 0-2-6-14-22-30-38-46-54
anti-drug antibodies		Week 0-2-6-14-22-30-38-46-54
fecal VDZ loss	The investigators will evaluated the VDZ quantity (microgram) that a patients with mucosal ulcers could loss in patients feces.	Week 0-2-6-14-22-30-38-46-54

Collaborators and Investigators

• Sponsor: Universita degli Studi di Genova

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Anticipated): March 1, 2019
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: May 17, 2016
• First Submitted That Met QC Criteria: June 28, 2016
• First Posted (Estimate): July 1, 2016

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease; Gastrointestinal Agents; Vedolizumab
• Other Study ID Numbers: EVeA Study