Acquired Immunodeficiency in ANCA (Antineutrophil Cytoplasmic Antibody) Associated Vasculitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 1
- 主要终点
- Comparison of the proportions of rituximab treated patients to disease controls who respond to the Pneumococcal Polysaccharide Conjugate vaccine. measured at 28 (+/- 7) days after administration of vaccine.
研究概览
简要总结
This study will address the following hypothesis: Rituximab therapy leads to an acquired immune deficiency, as demonstrated by impaired vaccine responses, in AAV patients.
Aims:
- To investigate whether rituximab leads to immune deficiency in patients with AAV when compared to both disease and healthy controls.
- To investigate whether the degree of immune deficiency is associated with the degree of B cell depletion.
- To investigate whether T-independent vaccine responses are more severely affected than T-dependent vaccine responses after rituximab and whether a conjugated vaccine will overcome this postulated deficit in T independent vaccine responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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)
- •For healthy controls:
- •Healthy individuals aged 40 years and over
排除标准
- •The presence of any of the following will preclude participant inclusion:
- •Age < 40 years
- •History of severe allergic or anaphylactic reactions to pneumococcal vaccinations
- •Pneumococcal vaccination within 5 years prior to screening
- •Females who are pregnant, plan to become pregnant, or breast feeding
- •Medical, psychiatric, cognitive or other conditions that, in the investigator's opinion, compromise the patient's ability to understand the patient information, give informed consent, comply with the trial protocol, or to complete the study.
- •History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure.
- •Replacement immunoglobulin (IVIg) administered intravenously or subcutaneously in the 12 weeks prior to screening visit.
- •For patients in Groups 1 and 2 only (AAV patients):
- •Presence of another multisystem autoimmune rheumatic disease
- •The prior receipt of more than 36g of cumulative cyclophosphamide ever (either IV or oral)
- •For patients in group 1 only (rituximab group)
- •The receipt of any immune suppressing agent (azathioprine, methotrexate or mycophenolate mofetil) after rituximab
- •For patients in Group 2 only (disease controls):
- •A relapse of AAV within the 6 months prior to screening which has necessitated an increase in prednisolone or azathioprine, methotrexate or MMF dose.
- •Previous rituximab therapy at any time
- •For healthy controls:
- •Any history of any autoimmune condition
- •Any history of use of immune suppressing medication, including > 4 weeks of oral glucocorticoids, within the 5 years prior to screening.
研究组 & 干预措施
AAV patients treated with rituximab
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
干预措施: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination (Biological)
AAV patients - never received rituximab
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
干预措施: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination (Biological)
Healthy controls
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
干预措施: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination (Biological)
结局指标
主要结局
Comparison of the proportions of rituximab treated patients to disease controls who respond to the Pneumococcal Polysaccharide Conjugate vaccine. measured at 28 (+/- 7) days after administration of vaccine.
时间窗: Measured at 28 (+/- 7) days after administration of vaccine.
Response is defined as at least a twofold increase in immunoglobulins in at least 6/13 pneumococcal serotypes tested.
Number of Rituximab Treated Patients Compared to Disease Controls Who Respond to the Pneumococcal Polysaccharide Conjugate Vaccine.
时间窗: Measured at 28 (+/- 7) days after administration of vaccine.
Response is defined as at least a twofold increase in immunoglobulins in at least 6/13 pneumococcal serotypes tested.
次要结局
- Number of serious adverse events, and serious adverse events specifically related to the vaccines administered(7 months: end of trial)
- Changes in immunoglobulin levels(7 months: end of trial)
- Immunoglobulin (IgG) titres for each individual serotype in the pneumococcal vaccine(Measured at month 0, 1, 6 and 7 in all participants)
- Incidence, type, severity and treatment of infections experienced by participants after vaccinations(7 months: end of trial)
- Number of Participants Who Have Responded by Individual Serotype in the Pneumococcal Vaccine(Measured at month 1 in all participants)
- Number of Participants Experiencing a Serious Adverse Event, or a Serious Adverse Event Specifically Related to the Vaccines Administered(7 months: end of trial)
- Number of Participants With Infections by Severity(7 months: end of trial)
- Changes in Immunoglobulin Levels(6 months: end of trial)
研究者
Dr. Rona Smith
Clinical lecturer in nephrology and experimental medicine
Cambridge University Hospitals NHS Foundation Trust