Acquired Immunodeficiency in ANCA Associated Vasculitis

NCT03514979 | Unknown Phase 2

• 1 other identifier: CCTU0155
• Study Type: interventional
• Target: 124
• Locations: 0 countries
• Sites: N/A

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. 1.To investigate whether rituximab leads to immune deficiency in patients with AAV when compared to both disease and healthy controls.
2. 2.To investigate whether the degree of immune deficiency is associated with the degree of B cell depletion.
3. 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

Outcome Measures

Primary Outcomes (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.

  Response is defined as at least a twofold increase in immunoglobulins in at least 6/13 pneumococcal serotypes tested.

  Measured at 28 (+/- 7) days after administration of vaccine.

Secondary Outcomes (4)

• Immunoglobulin (IgG) titres for each individual serotype in the pneumococcal vaccine

  Measured at month 0, 1, 6 and 7 in all participants

• Number of serious adverse events, and serious adverse events specifically related to the vaccines administered

  7 months: end of trial

• Incidence, type, severity and treatment of infections experienced by participants after vaccinations

  7 months: end of trial

• Changes in immunoglobulin levels

  7 months: end of trial

Study Arms (3)

AAV patients treated with rituximab

EXPERIMENTAL

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

Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

AAV patients - never received rituximab

EXPERIMENTAL

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

Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Healthy controls

EXPERIMENTAL

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

Biological: Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination

Interventions

Pneumococcal Polysaccharide Conjugate vaccination and Pneumococcal Polysaccharide Vaccination BIOLOGICAL

Pneumococcal vaccines

Also known as: Prevnar 13 and Pneumovax

AAV patients - never received rituximab; AAV patients treated with rituximab; Healthy controls

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Cambridge University Hospitals NHS Foundation Trust: lead
• Arthritis Research UK: collaborator

MeSH Terms

Conditions

Systemic Vasculitis

Interventions

13-valent pneumococcal vaccine; Pneumococcal Vaccines

Condition Hierarchy (Ancestors)

Vasculitis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Streptococcal Vaccines; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical lecturer in nephrology and experimental medicine

Model Details: 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.

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: May 3, 2018
• Study Start: June 1, 2018
• Primary Completion: July 1, 2020
• Study Completion: January 1, 2021
• Last Updated: May 3, 2018

Record last verified: 2018-05