Pneumococcal vaccine responses in ANCA associated vasculitis MedDRA version: 20.1 Level: PT Classification code 10050894 Term: Anti-neutrophil cytoplasmic antibody positive vasculitis System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Product Name: Pneumococcal polysaccharide conjugate vaccine
Pharmaceutical Form: Suspension for injection in pre-filled syringe
Product Name: Pneumococcal Polysacchari
Sponsors
Cambridge University Hospital NHS Foundation Trust and University of Cambridge
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be included in the trial all participants must: • Have given written informed consent to participate • Be aged 40 years and over For patients in Group 1 only (rituximab treated): • Have a diagnosis of AAV [granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (eGPA)] • Have current or historical PR3/MPO ANCA positivity by ELISA or histological confirmation of AAV • Have received = 2g rituximab • Have received their last dose of rituximab at least 12 months prior to enrolment • Be in stable remission with a prednisolone dose of = 5mg/day For patients in Group 2 only (disease controls who have never received rituximab): • Have a diagnosis of AAV (GPA, MPA or eGPA) • Have current or historical PR3/MPO ANCA positivity by ELISA or histological confirmation of AAV • Have received cyclophosphamide (oral or IV) as initial induction therapy • Be on stable immunosuppression for the 6 months preceding screening including prednisolone = 5mg/day AND either azathioprine, methotrexate or mycophenolate mofetil (at stable or tapering dose) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 62 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 62
Exclusion criteria
Exclusion criteria: The presence of any of the following will preclude participant inclusion: • Age 4 weeks of oral glucocorticoids, within the 5 years prior to screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does rituximab (a newer drug, which depletes B cells (a type of cell of the immune system which is important in fighting infections and responding to vaccines), and is increasingly being used to treat patients with AAV) impair the immune system, meaning that patients do not respond to vaccines as well as patients treated with other agents and suffer more infections? ; Secondary Objective: Does how well an individual responds to the vaccine depend on the number of B cells (a type of cell of the immune system which is important in fighting infections and responding to vaccines) that have returned following rituximab treatment? As less than 1 in 5 patients are predicted to respond to one dose of pneumococcal vaccine, is it possible to boost the response by administering a further dose 6 months after the initial vaccination? ;Primary end point(s): The primary outcome will compare the proportions of rituximab treated patients to disease controls who respond to the conjugated pneumococcal vaccine. Response is defined as at least a twofold increase in immunoglobulins titres in at least 6/13 of the pneumococcal serotypes tested. ;Timepoint(s) of evaluation of this end point: The primary endpoint will be measured at 28 (+/- 7) days after administration of the pneumococcal polysaccharide conjugate vaccine. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In view of the lack of validation of any primary endpoint defining response to pneumococcal vaccination, the secondary outcome measures in this study are extremely important. 1. Immunoglobulin (IgG) titres for each individual serotype in the pneumococcal vaccine will be measured at month 0, 1, 6 and 7 in all participants. 2. PBMC extraction and immunophenotyping of circulating B cell sub-populations (CD27+ memory cells CD19+ B cells and CD27-/ CD19+ naïve B cells) and T cell sub-populations. 3. Number of serious adverse events, and serious adverse events specifically related to the vaccines administered (serious adverse reactions) 4. Incidence, type, severity and treatment of infections experienced by participants after vaccinations 5. Changes in immunoglobulin levels will be measured over time ; Timepoint(s) of evaluation of this end point: Immunoglobulin titres for each individual serotype in the pneumococcal vaccines will be performed at month 0, 1, 6 and 7. B and T cell immunophenotyping will be performed in a subset of patients and month 0,1,6 and 7. All severe adverse events, infections and adverse events specifically related to the vaccines administered will be collected until a subject's participation in the trial is completed at 7 months. | — |
Countries
United Kingdom
Contacts
Public ContactCarrie Bayliss
CCTU
Outcome results
None listed