Vaccination Against Pneumococcal in Naïve Abatacept Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

— VACINA  

Official title:

Comparison of Humoral Response to Conjugate Pneumococcal Vaccine and Polysaccharide Pneumococcal Vaccine in Rheumatoid Arthritis (RA) Patients Treated With Abatacept

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02547493
• Other study ID #: 9419
• Status: Completed
• Phase: N/A
• Start date: March 3, 2016
• Est. completion date: January 18, 2021

Study information

• Verified date: December 2021
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Is pneumococcal conjugate vaccine (which induces a T-dependent humoral response) more efficient than pneumococcal polysaccharide vaccine (which induces a T-independent humoral response) in RA patients treated with abatacept, biotherapy targeting T-cells? The investigator propose to conduct a prospective, multicenter (11 centers), randomized, open-label study.

The patients are going to be randomized in 2 groups: patients of the first group will be vaccinated with the polysaccharide pneumococcal vaccine (Pneumo23®/Pneumovax®) whereas patients of the second group will be vaccinated with conjugate pneumococcal vaccine (Prevenar13®).

Description:

The study population will be all the RA patients between 18 and 85 years with instauration of a treatment by sub-cutaneous abatacept in association with methotrexate who agreed to participate to the study.

At the time of their inclusion, patients will be randomized for receiving either pneumococcal polysaccharide vaccine (PPSV) or pneumococcal conjugate vaccine (PCV).

The primary endpoint will be evaluated at one month after vaccination. The total of follow-up will be of 12 months.

For the patients of the group PCV, the prime-boost strategy will be applied in order to be in accordance with the current French recommendation and a revaccination at 2 months after the initial vaccine will be realized with PPSV.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: January 18, 2021
• Est. primary completion date: January 18, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• RA according to American College of Rheumatology (ACR)/European League Against rheumatism (EULAR) 2010 criteria

• Disease Activity Score (DAS) 28 = 3.2

• Initiation of a treatment by sub-cutaneous abatacept in combination with methotrexate (MTX), whatever treatment they were receiving before (apart from rituximab (RTX) in the last year)

• Patient has signed study consent form

Exclusion Criteria:

• age < 18 or > 85 year

• dementia

• patients subjects to legal protection measures

• Corticosteroids = 10mg/d the day of inclusion

• Patient who had a pneumococcal vaccination in the previous 3 years

• Last pneumococcal vaccination < 3 year

• rituximab in the last year

• History of anaphylactic response to a vaccination

• Contraindications to abatacept or methotrexate

• Pregnancy or pregnancy wish

• Breast feeding

• Patient who currently abuse drugs or alcohol

• Subject who have received any live vaccines within 3 months of the anticipated first dose of study medication.

• Subject who have receive any vaccine within 1 month of the anticipated first dose of the study medication and for all the duration of the study

• Patient with contraindication to intramuscular injections

• Subject with respiratory insufficiency

• Subject at risk for Tuberculosis.

• Blood transfusion within the 3 months previous to the study and for all the duration of the study.

• Concomitant biologic disease-modifying antirheumatic drug (DMARD)

• Within 4 weeks of receiving treatment with any investigational drug.

• Patient positive for hepatitis B surface antigen

• Patient who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• pneumococcal polysaccharide vaccine
Vaccination with PPSV on first day. NB : PPSV vaccine Pneumo23 has been replaced in September 2017 by the equivalent vaccine Pneumovax because of the stop of commercialization of Pneumo23 in France by the pharmaceutical company.
• pneumococcal conjugate vaccine
Patients are vaccinated with Prevenar13 on the first day, and with Pneumo23/Pneumovax two months later.

Drug:
• Abatacept
Abatacept started on frst day

Locations

Country	Name	City	State
France	CHU Nord	Amiens
France	CHU Pellegrin	Bordeaux
France	CHU Montpied	Clermont-Ferrand
France	CHU Bicêtre	Le Kremlin-bicêtre
France	CHRU Roger Salengro	Lille
France	CHRU de Montpellier	Montpellier	Hérault
France	CHU Carémeau	Nîmes
France	CHU Orléans	Orléans
France	CHU La pitié salpétriere	Paris
France	CHU Hautepierre	Strasbourg
Monaco	CHPG Monaco	Monaco

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Bristol-Myers Squibb

Countries where clinical trial is conducted

France,  Monaco, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Humoral response comparison after vaccination (number of patient with at least a two-fold increase of the antibody titer for at least 3 of the 5 serotypes of interest : 1,3 14, 7F, 19A)	To compare the rate of responders, at one month after vaccination, between patients vaccinated with PCV and patient vaccinated with PPSV.	1 month after vaccination
Secondary	Side Effect frequency (number of side effect at each patient's visit for both groups)	Comparison of the frequency of side effects between the 2 groups at 1, 2, 6 and 12 months	1, 2,6 ans 12 months after inclusion
Secondary	Prime boost strategy efficacity evaluation (number of responder in the PCV group)	Calculation of the rate of responders, in the PCV group, at 4 month after re-vaccination by a dose of PPSV	6 months after inclusion
Secondary	Long term immune response after vaccination	Comparison between the 2 groups of the rate of responders at 6 and 12 months after vaccination	6 and 12 months after vaccination
Secondary	Comparison between the 2 groups of the opsonophagocytosis activity of the antibodies produced	Comparison between the 2 groups of the opsonophagocytic titers (OPA) at 1, 2, 6 and 12 months after vaccination	1, 2, 6 and 12 months after vaccination
Secondary	Pneumococcal vaccination predictive factor identification	Analysis of the collected date to search for predictive factors of immune response after pneumococcal vaccination by comparison of the rates of responders within each group, according to age, gender, RA activity, MTX dosage, corticosteroid, dosage, therapeutical history	12 month after last patient inclusion