Shingrix in Patients With Rheumatic Diseases: a Double-blind Placebo-controlled RCT

Study Overview
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Brief Summary
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A double-blind randomized controlled trial on the safety and immunogenicity of the recombinant subunit herpes zoster vaccine, Shingrix, in patients with rheumatic diseases undergoing immunosuppressive or biologic/targeted DMARD therapies

Detailed Description
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A double-blind randomized controlled trial on the safety and immunogenicity of the recombinant subunit herpes zoster vaccine, Shingrix, in patients with rheumatic diseases undergoing immunosuppressive or biologic/targeted DMARD therapies. Duration of study: 60 weeks

Official Title
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Safety and Immunogenicity of a Recombinant Subunit Herpes Zoster Vaccine in Patients With Rheumatic Diseases Undergoing Immunosuppressive or Biologic/Targeted DMARD Therapies: a Double-blind Randomized Placebo-controlled Trial

Conditions
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Herpes Zoster

Intervention / Treatment
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* Biological: recombinant subunit herpes zoster vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for patients: Patients with a diagnosis of rheumatic or immune-mediated diseases eg. SLE, RA, PSA, SpA, inflammatory myopathies, ANCA-related and large vessel vasculitides Age ≥18 years Stable or reducing doses of any the following immunosuppressive regimens within 4 weeks of study entry: Prednisolone ≥20mg/kg/day ± mycophenolate mofetil, azathioprine or the calcineurin inhibitors Cyclophosphamide (intravenous pulses or daily oral) B-cell depleting biological agents and their biosimilars eg. belimumab, anti-CD20 agents (next scheduled dose should be arranged to at least 12 weeks after study entry for rituximab or obinutuzumab) Anti-TNFα biological agents and their biosimilars eg. infliximab, etanercept, adalimumab, golimumab, certolizumab Anti-interleukin-6 biological agents eg. tocilizumab, sarilumab Other biological agents eg. abatacept, ustekinumab, secukinumab, ixekizumab The JAK inhibitors eg. tofacitinib, baricitinib, upadacitinib Female patients with reproductive potential are allowed to participate in this study provided that they are willing to practice contraception for until at least 12 months after vaccination Willing to comply with all study procedures Exclusion criteria for patients: Active infection, including upper respiratory tract infection Active HZ infection Active untreated tuberculosis HIV infection History of HZ or varicella vaccination in the past History of allergy to any vaccines Patients who are pregnant or plan to become pregnancy within one year of study entry Lactating women Patients who cannot give a written consent (mentally incapable or illiterate)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: vaccine<br>Shingrix vaccine | Biological: recombinant subunit herpes zoster vaccine<br>* vaccine administration<br>* Other names: Shingrix;|
| Placebo Comparator: placebo<br>normal saline injection (0.5mL) | Biological: recombinant subunit herpes zoster vaccine<br>* vaccine administration<br>* Other names: Shingrix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| humoral immune response to Shingrix | proportion of patients with 4x fold increase in anti-gE antibody titer | week 12 (compared with baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Humoral immune response | proportion of patients with 4x fold increase in anti-gE antibody titer | week 52 | 
| adverse events | solicited | 7 days after injection | 
| adverse events | unsolicited | 4 weeks after injection | 
| flares of underlying diseases | disease flares | week 26 and 60 | 
| herpes zoster infection | herpes zoster infection | week 60 | 
| cell mediated response to vaccine | in 40 patients (20 from each arm); number of IFNγ-secreting CD4+ T cell colonies on ELISPOT assay | week 12 from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, rheumatic diseases, immunosuppressive, immunogenicity, biologics, targeted DMARDs