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Acquired Immunodeficiency in ANCA Associated Vasculitis (ACQUIVAS)

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ClinicalTrials.gov Identifier: NCT03514979
Recruitment Status : Not yet recruiting
First Posted : May 3, 2018
Last Update Posted : May 3, 2018
Sponsor:
Collaborator:
Arthritis Research UK
Information provided by (Responsible Party):
Dr. Rona Smith, Cambridge University Hospitals NHS Foundation Trust

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.

Condition or disease Intervention/treatment Phase
Systemic Vasculitis Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a phase IIb, open label study to evaluate the responses of patients with ANCA associated vasculitis (AAV) to pneumococcal vaccination. It has been designed primarily to assess the immunogenicity of pneumococcal vaccines in patients with AAV treated with rituximab compared to disease controls, but also to provide mechanistic information on vaccine response by comparing AAV patients and healthy controls.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Acquired Immunodeficiency in ANCA (Antineutrophil Cytoplasmic Antibody) Associated Vasculitis
Estimated Study Start Date : June 2018
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vasculitis

Arm Intervention/treatment
Experimental: AAV patients treated with rituximab
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination
Pneumococcal vaccines
Other Name: Prevnar 13 and Pneumovax

Experimental: AAV patients - never received rituximab
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination
Pneumococcal vaccines
Other Name: Prevnar 13 and Pneumovax

Experimental: Healthy controls
Pneumococcal Polysaccharide Conjugate vaccination at Month 0 and then Pneumococcal Polysaccharide Vaccination at Month 6.
Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination
Pneumococcal vaccines
Other Name: Prevnar 13 and Pneumovax




Primary Outcome Measures :
  1. 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. [ Time Frame: 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.


Secondary Outcome Measures :
  1. Immunoglobulin (IgG) titres for each individual serotype in the pneumococcal vaccine [ Time Frame: Measured at month 0, 1, 6 and 7 in all participants ]
    Immunoglobulin (IgG) titres for each individual serotype in the pneumococcal vaccine

  2. Number of serious adverse events, and serious adverse events specifically related to the vaccines administered [ Time Frame: 7 months: end of trial ]
    Number of serious adverse events, and serious adverse events specifically related to the vaccines administered

  3. Incidence, type, severity and treatment of infections experienced by participants after vaccinations [ Time Frame: 7 months: end of trial ]
    Incidence, type, severity and treatment of infections experienced by participants after vaccinations

  4. Changes in immunoglobulin levels [ Time Frame: 7 months: end of trial ]
    Changes in immunoglobulin levels



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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.

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Responsible Party: Dr. Rona Smith, Clinical lecturer in nephrology and experimental medicine, Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT03514979     History of Changes
Other Study ID Numbers: CCTU0155
First Posted: May 3, 2018    Key Record Dates
Last Update Posted: May 3, 2018
Last Verified: May 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Vasculitis
Systemic Vasculitis
Immunologic Deficiency Syndromes
Immune System Diseases
Vascular Diseases
Cardiovascular Diseases
Rituximab
Vaccines
Antibodies, Antineutrophil Cytoplasmic
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents