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

NCT04064697 | Terminated Phase 3 DMC

• 2 other identifiers: 18PH1922019-001032-54
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 8

Brief Summary

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).

Conditions

Ulcerative Colitis, Unspecified

Keywords

Ulcerative Colitis (UC); CytoMegaloVirus (CMV); Vedolizumab; Valganciclovir; Anti-TNF; Mayo score

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Clinical remission

  Weeks 6

• Mucosal healing

  Weeks 6

• Viral load CytoMegaloVirus (CMV)

  Weeks 6

• clinical remission

  Weeks 52

• Rate of colectomy

  Weeks 52

Study Arms (2)

Control group

NO INTERVENTION

Patient will be treated by vedolizumab the standard of care alone.

Experimental group

EXPERIMENTAL

Patient will be treated by vedolizumab the standard of care associated at valganciclovir.

Drug: Valganciclovir

Interventions

Valganciclovir DRUG

The experimental intervention consists of taking the treatment Valganciclovir 900 mg morning and evening for 3 weeks

Also known as: antiviral therapy

Experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Saint Etienne: lead
• Ministry of Health, France: collaborator

Study Sites (8)

CH d'Annecy

Annecy, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, France

Location

CHU de Lyon Sud

Lyon, France

Location

CHU de Montpellier

Montpellier, France

Location

CHU de Nice

Nice, France

Location

APHP - Hôpital Saint-Antoine

Paris, France

Location

CHU ROUEN - Service Gastro-entérologie

Rouen, France

Location

CHU de Saint Etienne

Saint-Etienne, France

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Pauline VEYRARD, MD

  CHU SAINT-ETIENNE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2019
• First Posted: August 22, 2019
• Study Start: April 22, 2021
• Primary Completion: November 23, 2023
• Study Completion: February 8, 2024
• Last Updated: April 10, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (8)