Impact of Anti-cytomegalovirus Treatment in the Management of Relapsing Ulcerative Colitis Requiring Vedolizumab Therapy (CYTOVEDO)

Impact of Anti-cytomegalovirus (Valganciclovir) Treatment in the Management of Relapsing Ulcerative Colitis (UC) Requiring Vedolizumab Therapy: a Randomized Clinical Trial Comparing a Strategy With or Without Antiviral Therapy.

Ulcerative Colitis (UC) is an inflammatory bowel disease that can require the use of anti-TNF alpha therapy. When anti-TNF alpha failed to obtain a clinical response, the use of a new anti-integrin therapy, vedolizumab, can be proposed. The efficacy of vedolizumab has been assessed in a phase 3 study (GEMINI I), with response rates of 41.1% with vedolizumab vs 25.5% with placebo.

CytoMegaloVirus (CMV) reactivation has been associated with resistance to steroid and to several lines of immunosuppressive therapy. Antiviral therapy was proven to decrease the tissue viral load and to restore the response to immunosuppressive therapies (up to 80% in small group of patients). A recent meta-analysis supports the use of valganciclovir in case of CytoMegaloVirus (CMV) reactivation in active Ulcerative Colitis (UC).

Moreover, a study showed that the risk of CMV reactivation seems to be more important with vedolizumab than with anti TNF, and the risk of colectomy is higher in case of CytoMegaloVirus (CMV) reactivation (p<0.05).

Study Overview

• Status: Terminated
• Conditions: Ulcerative Colitis, Unspecified
• Intervention / Treatment: Drug: Valganciclovir

Detailed Description

The hypothesis of this study is in Ulcerative Colitis (UC) patients with tissue CytoMegaloVirus (CMV) reactivation ; not responding to anti-TNF or without anti-TNF ; a treatment with valganciclovir, added to vedolizumab, could improve the clinical response.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Pauline VEYRARD, MD; Phone Number: +33 (0)477828619; Email: pauline.veyrard@chu-st-etienne.fr
• Study Contact Backup: Name: Marie PEURIERE, CRA; Phone Number: +33 (0)477120826; Email: Marie.Peuriere@chu-st-etienne.fr

Study Locations

• France
  • Annecy, France
    • CH d'Annecy
  • Clermont-Ferrand, France
    • CHU de Clermont-Ferrand
  • Lyon, France
    • CHU de Lyon Sud
  • Montpellier, France
    • CHU de Montpellier
  • Nice, France
    • CHU de Nice
  • Paris, France
    • APHP - Hôpital Saint-Antoine
  • Rouen, France
    • CHU ROUEN - Service Gastro-entérologie
  • Saint-Étienne, France
    • CHU de Saint Etienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient with moderate to severe active Ulcerative Colitis (UC) defined by a Mayo score greater than 5

• Patient with an inflammatory outbreak of Ulcerative Colitis (UC) :

  • without anti-TNF
  • under anti-TNF (infliximab, adalimumab, golimumab) after induction (no primary response) or clinical recurrence (secondary failure).
• Having rectosigmoidoscopy with an endoscopic Mayo score≥ 2 with 2 biopsies of the inflammatory tissue
• Presence of a CytoMegaloVirus (CMV) infection in the inflammatory tissue (viral load greater than 5 IU / 100000 cells by qPCR)
• Patient with a negative pre-treatment assessment including HIV, HBV, HCV, HCV serology, a negative quantiferon or a history of tuberculosis preventive treatment adapted by Rifinah or Rimifon
• Signed informed consent

Exclusion Criteria:

• Patient with severe acute colitis
• Patient treated by ciclosporin or Prograf
• Patient with Human Immunodeficiency Virus (HIV)+, hepatitis B, hepatitis C, tuberculosis
• Clostridium difficile infection.
• Patient with intolerance or contraindications to current therapy
• Pregnant or starts breastfeeding
• Patient who received a live vaccine in the month preceding the study
• Patients with severe renal insufficiency defined by creatinine clearance <30ml/minute, or hemodialysed

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control group; Patient will be treated by vedolizumab the standard of care alone.
Experimental: Experimental group; Patient will be treated by vedolizumab the standard of care associated at valganciclovir.	Drug: Valganciclovir; The experimental intervention consists of taking the treatment Valganciclovir 900 mg morning and evening for 3 weeks; Other Names: antiviral therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Percentage of patients in clinical response. the clinical response is defined by the decrease in the total Mayo Score compared to the inclusion of at least 3 points and at least 30% with a decrease in the score of bleeding (item 2 of the Mayo sub-score) from at least one point or sub-score of bleeding from 0 or 1 point with or without anti-CMV treatment. The Mayo score includes 3 items: stool frequency, presence of blood in the stool, and overall assessment of the disease.	Weeks 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission	Percentage of patients in clinical remission defined by a total Mayo score <3 with an endoscopic score <2 and no clinical sub-score> 2.	Weeks 6
Mucosal healing	Percentage of patients in mucosal healing defined by endoscopic mayo score <2	Weeks 6
Viral load CytoMegaloVirus (CMV)	Value of viral load CytoMegaloVirus (CMV) by qPCR on inflammatory tissue in IU / 100000 cells.	Weeks 6
clinical remission	Percentage of patients in clinical remission defined by a total Mayo score <3 with an endoscopic score <2 and no clinical sub-score> 2.	Weeks 52
Rate of colectomy	Percentage of patients who required colectomy	Weeks 52
Adverse effects	Number and severity of adverse effects	Weeks 52
viral load of the Torque teno virus	performed on the blood tube and tissue biopsies	Week 6

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Ministry of Health, France
• Investigators: Principal Investigator: Pauline VEYRARD, MD, CHU Saint-Etienne

Study record dates

Study Major Dates

• Study Start (Actual): April 22, 2021
• Primary Completion (Actual): November 23, 2023
• Study Completion (Actual): February 8, 2024

Study Registration Dates

• First Submitted: August 20, 2019
• First Submitted That Met QC Criteria: August 20, 2019
• First Posted (Actual): August 22, 2019

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Anti-TNF; Ulcerative Colitis (UC); Mayo score; Vedolizumab; Valganciclovir; CytoMegaloVirus (CMV)
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: 18PH192; 2019-001032-54 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No