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

Immunogenicity of a Combined Anti-pneumococcal Vaccine Schedule in Patients With ANCA-associated Vasculitis: a Pilot Study Following New Vaccine Recommendations. PneumoVas Pilot 2

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).

Study Overview

• Status: Unknown
• Conditions: ANCA-associated Vasculitis; Pneumococcal Infection

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 Type: Observational
• Enrollment (Anticipated): 30

Contacts and Locations

• Study Contact: Name: Matthieu Groh, MD, MSc; Email: matthieu.groh@cch.aphp.fr
• Study Contact Backup: Name: Anaïs Maugard; Email: anais.maugard@aphp.fr

Study Locations

• France
  • Ile de France
    • Paris, Ile de France, France, 75014
      • Recruiting
      • AP-HP ; Cochin Hospital
      • Contact: Matthieu Groh; Email: matthieu.groh@cch.aphp.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients followed for ANCA-associated Vasculitis

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-pneumococcal immunity after combined anti-pneumococcal immunization	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	visit V1 (12 to 16 weeks after V0 (Day 0))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess serotype 3, 4, 6B, 7F, 9V, 14, 18C, 19 A, 19F and 23F-specific immune responses after vaccination	ELISA specific antibody titres to serotype 3, 4, 6B, 7F, 9V, 14, 18C, 19 A, 19F and 23F.	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).
To assess serotype coverage increase after PPV23 injection	Serotype 10A and 12F (e.g. 2 PPV23-specific serotypes) ELISA antibody concentrations	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).
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.	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.	visit V0 (Day 0), visit V1(12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).
Change Outcome Measures-To assess the sustainability and evolution over time of the vaccine-induced immune response (ELISA and OPA)	For ELISA-responding patients at V1, antibody ELISA concentrations and OPA titers will be measured 52 weeks after PCV13 injection (V2).	visit V2 (48 to 56 weeks after V0).
Composite Outcome Measures - To identify epidemiologic, clinic and biologic predictive factors that may influence vaccine-induced immune response.	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	visit V0 (Day 0), visit V1 (12 to 16 weeks after V0) and visit V2 (48 to 56 weeks after V0).

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Matthieu Groh, MD, MSc, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Anticipated): May 1, 2018
• Study Completion (Anticipated): November 1, 2018

Study Registration Dates

• First Submitted: May 12, 2015
• First Submitted That Met QC Criteria: June 3, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): February 25, 2016
• Last Update Submitted That Met QC Criteria: February 24, 2016
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Vaccinology; Immunocompromised; Pneumococcal infection; Invasive pneumococcal disease (IPD); Pneumococcal vaccine; Systemic vasculitis; ANCA-associated vasculitis; Auto-immune diseases
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Systemic Vasculitis; Pneumococcal Infections; Vasculitis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
• Other Study ID Numbers: NI15002