Immunogenicity of a Combined Anti-pneumococcal Vaccine Schedule in Patients With ANCA-associated Vasculitis

• Conditions: Pneumococcal Infection; ANCA-associated Vasculitis

• Registration Number: NCT02463578
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Exploratory study of anti-pneumococcal immune response in patients with Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) immunized according to new vaccine recommendations (i.e. with a combined vaccine schedule (13-valent conjugate pneumococcal vaccine -PCV13- followed by a 23-valent non-conjugate pneumococcal vaccine -PPV23- 8 weeks later).

Detailed Description

The purpose of this study is to determine whether this vaccination schedule induces sufficient protective immunity (serotype-specific enzyme linked immunosorbent assay (ELISA) and opsonophagocytosis (OPA) response rates) in AAV-patients receiving immunosuppressive therapy.

Study Timeline

• Study First Submitted: 2015-05-12
• Study Start: 2015-06
• Study First Submitted QC: 2015-06-03
• Study First Posted: 2015-06-04
• Status Verified: 2015-12
• Last Update Submitted: 2016-02-24
• Last Update Posted: 2016-02-25
• Primary Completion: 2018-05
• Study Completion: 2018-11

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Age ≥ 18 years
• ANCA-associated vasculitis: diagnosis of granulomatosis with polyangiitis, microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis according to American College of Rheumatology criteria
• Indication for pneumococcal vaccination according to French recommendations (statement of the Haut Conseil de Santé Publique regarding pneumococcal vaccination for adults and children older than 2 years old at risk for invasive pneumococcal disease, April 25Th 2013)

Exclusion Criteria

• History of pneumococcal immunization 36 months to 24hours before VO.
• Patients with known, or suspected pregnancy
• Patients planning to get pregnant in the year following inclusion
• Splenectomy
• Eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss) flare
• Infection during the week before inclusion
• Patient without social security coverage
• Individuals opposal

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Anti-pneumococcal immunity after combined anti-pneumococcal immunization	visit V1 (12 to 16 weeks after V0 (Day 0))	Proportion of responder patients at V1 (12-weeks after PCV13 injection) to at least 6 of the 10 shared serotypes (i.e. 3, 4, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) included both in PCV13 and PPV23. A serotype is considered positive if the ELISA immunoglobulins G (IgG) antibody titter shows a two-fold increase from baseline (V0) to V1 and is ≥ 1 μg/ml

Secondary Outcome Measures

Name	Time	Method
To assess serotype 3, 4, 6B, 7F, 9V, 14, 18C, 19 A, 19F and 23F-specific immune responses after vaccination	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).	ELISA specific antibody titres to serotype 3, 4, 6B, 7F, 9V, 14, 18C, 19 A, 19F and 23F.
Change Outcome Measures-To assess the sustainability and evolution over time of the vaccine-induced immune response (ELISA and OPA)	visit V2 (48 to 56 weeks after V0).	For ELISA-responding patients at V1, antibody ELISA concentrations and OPA titers will be measured 52 weeks after PCV13 injection (V2).
To assess serotype coverage increase after PPV23 injection	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).	Serotype 10A and 12F (e.g. 2 PPV23-specific serotypes) ELISA antibody concentrations
Composite Outcome Measures - To identify epidemiologic, clinic and biologic predictive factors that may influence vaccine-induced immune response.	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).	Analysis of epidemiological, clinical and biological data collected during follow-up: age, sex, history of immunosuppressive therapy, time since previous PPV23 injection, number of previous PPV23 immunizations, AAV activity and severity according to Birmingham Vasculitis Activity Score and Vasculitis Damage Index, results of biological analyses
For the following serotypes (4, 6B, 9V, 14, 18C, 19F and 23F), to assess the proportion of ELISA-responding patients who also show in vitro opsonophagocytic antibody activity.	visit V0 (Day 0), visit V1(12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).	For each of the following serotypes (4, 6B, 9V, 14, 18C, 19F and 23F), OPA titers will be measured in ELISA-responding patients at V0, V1, V2. Opsonophagocytic antibody activity is considered positive if the antibody titer shows a four-fold increase from V0 and is above a serotype-specific predefined threshold.

Trial Locations

Locations (1)

AP-HP ; Cochin Hospital; 🇫🇷 Paris, Ile de France, France