Acquired Immunodeficiency in ANCA Associated Vasculitis

NCT ID: NCT03514979

Last Updated: 2018-05-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-30
• Study Completion Date: 2021-01-31

Brief Summary

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:

1. To investigate whether rituximab leads to immune deficiency in patients with AAV when compared to both disease and healthy controls.

2. To investigate whether the degree of immune deficiency is associated with the degree of B cell depletion.

3. 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.

Conditions

Systemic Vasculitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

AAV patients treated with rituximab

Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.

Group Type: EXPERIMENTAL

Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Intervention Type: BIOLOGICAL

Pneumococcal vaccines

AAV patients - never received rituximab

Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.

Group Type: EXPERIMENTAL

Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Intervention Type: BIOLOGICAL

Pneumococcal vaccines

Healthy controls

Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.

Group Type: EXPERIMENTAL

Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Intervention Type: BIOLOGICAL

Pneumococcal vaccines

Interventions

Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Pneumococcal vaccines

Intervention Type: BIOLOGICAL

Other Intervention Names

Prevnar 13 and Pneumovax

Eligibility 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)

For healthy controls:

• Healthy individuals aged 40 years and over

Exclusion Criteria

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Arthritis Research UK

OTHER

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

Dr. Rona Smith

Clinical lecturer in nephrology and experimental medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Other Identifiers

CCTU0155

Identifier Type: -

Identifier Source: org_study_id