Anti-pneumococcal Vaccine Strategy in Patients Treated With Immunosuppressants or Biotherapies for CIBD (PneumoMICI)

Phase IIb Multicenter Randomized Comparative Study of Anti-pneumococcal Vaccine Strategy in Patients Treated With Immunosuppressants or Biotherapies for Chronic Inflammatory Bowel Disease

This is a multicenter, prospective, randomized, open study comparing two anti-pneumococcal vaccination strategies in patients with Chronic Inflammatory Bowel Disease (CIBD) treated by immunosuppressants and/or biotherapies. At present such patients are poorly protected by anti-pneumococcal vaccination. In addition, vaccination efficacy in this type of patient is much weaker than in the general population. There are two types of anti-pneumococcal vaccines: firstly a polysaccharide, Pneumo23® (PSV-23®) vaccine and secondly a conjugate, Prevenar13® vaccine. New recommendations have just been issued by the HSCP advising immunocompromised patients to follow a vaccination plan combining one dose of Prevenar13® followed by one dose of PSV-23® after an interval of two months. In the case of young children infected with HIV, the recommendation is to multiply doses of Prevenar13® before the PSV-23® injection to improve vaccine efficacy in these immunocompromised patients.

Our study aims to identify an optimal vaccination strategy for immunocompromised CIBD patients by combining use of a conjugate vaccine, Prevenar13® and a polysaccharide vaccine, PSV-23®. We will compare the use of one or two doses (M0 +/- M2) of Prevenar13® combined with a later PSV-23® injection (M4) on vaccination immunogenicity measured by antibody titer against at least nine of the thirteen pneumococcal serotypes contained in Prevenar13®. We also want to evaluate the immunological impact of these different strategies in their capacity to stimulate a memory B anti-pneumococcal response more effectively. With this aim, we are studying all immunological functional aspects of the antibodies and B lymphocytes induced by the two vaccine strategies.

Study Overview

• Status: Terminated
• Conditions: Bowel Diseases, Inflammatory; Infections, Pneumococcal
• Intervention / Treatment: Biological: Prevenar 13; Biological: Pneumo 23

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Amiens, France
    • CHU Amiens-Picardie
  • Besançon, France, 25030
    • Hopital Jean Minjoz
  • Montpellier, France, 34295
    • Hôpital Saint-Eloi
  • Nice, France, 06202
    • Hôpital de l'Archet II
  • Paris, France
    • APHP - Hôpital Cochin
  • Pierre Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
  • Rouen, France, 76031
    • Hopital Charles Nicolle
  • Saint-Etienne, France, 42055
    • 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 who have given their written consent in a free and informed consent
• Patient followed for inflammatory bowel disease (Crohn's disease, ulcerative colitis or indeterminate colitis), and treated for at least 3 months by immunosuppressive therapy and /or biotherapies and in clinical remission for at least 3 months
• Patient agreeing to participate in the study throughout its duration and accepting the procedures related to the study
• Contraception that the investigator judges effective for the first 12 months of the trial, with a negative pregnancy test
• Women not planning to become pregnant in the 12 months following inclusion (M0)
• Patient with social coverage

Exclusion Criteria:

• Patients vaccinated against pneumo23 for less than 5 years
• Other vaccination during the month before inclusion
• Patient develops a febrile illness (at least 37 ° C 5 measured orally) or acute infection in the week before vaccination
• The patient has a flare up of IBD the day of vaccination (Harvey-Brasdshaw score of at least 6 or CDAI > 220 for Crohn's disease or Mayo Clinic score of at least 4 for UC and indeterminate colitis)
• Patients with an ongoing pregnancy the day of vaccination
• Patient with a known history of neuropathy as Guillain-Barré syndrome.
• Patients with known infection with HIV and / or HBV (HBsAg positive) and / or HCV
• Patient with other severe immune deficiency
• Patients who received immunoglobulin infusions of blood products, or of monoclonal antibodies (except anti-TNF) in the 3 months prior to vaccination
• Patient institutionalized, or deprived of liberty administrative or judicial
• Patients treated without immunosuppressive therapy or biotherapies

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1 dose Prevenar13 and 1 dose PSV23; one dose of the polysaccharide vaccine, Prevenar 13 at M0 and one dose of polysaccharide vaccine, Pneumo 23 at M4	Biological: Prevenar 13; one dose for arm 1 and 2 doses for arm 2; Biological: Pneumo 23; one dose
Experimental: 2 doses Prevenar13 and 1 dose PSV23; one dose of the polysaccharide vaccine, Prevenar 13 at M0, one dose of the polysaccharide vaccine, Prevenar 13, at M2 and one dose of polysaccharide vaccine, Pneumo 23 at M4	Biological: Prevenar 13; one dose for arm 1 and 2 doses for arm 2; Biological: Pneumo 23; one dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with anti-pneumococcal immunogenicity	Measured the serologies against serotypes to Prevenar 13. Serotype to be measured are 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A 19 F and 23F using the ELISA method	month 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with local and/or general reaction	self monitoring diary	Months 1, 3 and 5
Number of patients with inflammatory disease activity	by clinic score HBI or CDAI or Mayo	Months 1, 3, 4, 5, 12, 18, 36
Factors implicated in anti-pneumococcal vaccination efficacy	questionnaire	Month 0
number of patients with serotype coverage of PSV-23	Measured the serologies against serotypes to Pneumo 23. Serotype to be measured are serotypes 10 and 15 using the ELISA method	Months 5, 12, 18 and 36

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Saint Etienne
• Collaborators: Pfizer
• Investigators: Principal Investigator: Xavier Roblin, MD, CHU SAINT-ETIENNE

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2015
• Primary Completion (Actual): August 6, 2019
• Study Completion (Actual): July 6, 2022

Study Registration Dates

• First Submitted: September 26, 2014
• First Submitted That Met QC Criteria: October 1, 2014
• First Posted (Estimated): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: June 13, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: vaccination; randomized; anti-pneumococcal; Pneumo 23; Prevenar 13; Chronic Inflammatory Bowel Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Inflammatory Bowel Diseases; Intestinal Diseases; Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: 1308162; 2013-004609-19 (EudraCT Number)

Drug and device information, study documents

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