Active — Not RecruitingPhase 4

Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases

Brazil2,005 participantsStarted 2023-05-23

Plain-language summary

Introduction: Patients with autoimmune rheumatic diseases (ARDs), rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), psoriatic arthritis (PAs), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) , systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM) and primary vasculitides, have a high risk of herpes zoster (HZ) infection. This increased susceptibility is caused by a deficient cell-mediated immune response due to the underlying disease and glucocorticoid and immunosuppressive treatments that impair the T-cell response, including conventional and unconventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) and biological agents. In this context, the recent availability of a recombinant vaccine against HZ (RZV or Shingrix®), composed of recombinant VZV glycoprotein E (gE) and the AS01B adjuvant system (HZ/su), is a major progress regarding safety for immunosuppressed patients. Its effectiveness, however, has been clearly demonstrated for non-immunosuppressed patients and in selected populations of immunocompromised individuals. There are no prospective controlled studies evaluating the immunogenicity of RZV and its impact on the activity of the underlying disease, as well as its safety in patients with ARDs at high-risk for HZ. Hypothesis: RZV has a good safety profile, including with respect to underlying rheumatic disease activity, in patients with ARDs at high risk of HZ. Objectives: Primary: To assess the short-term safety profile in relation to underlying disease activity in patients with ARDs at high risk of HZ immunized with RZV compared to unvaccinated patients. Secondary: To evaluate the general safety of the vaccine in patients with ARDs at high risk of HZ immunized with RZV and non-immunosuppressed control subjects (CG); the humoral and cellular immunogenicity of RZV in patients with ARDs at high risk of HZ compared to CG; the influence of disease treatment on vaccine response; the 12-month persistence of humoral immunogenicity and incident cases of HZ. Specific studies will also be carried out to evaluate the effect of drug withdrawal (methotrexate-MTX and mycophenolate mofetil-MMF) after vaccination in increasing the immune response in patients with ARDs with controlled underlying disease. On November 19, 2025, the institutional Ethics Committee approved an amendment to extend the project's timeframe to evaluate the following hypothesis: \- Immunosuppression may hamper 5-year long-term sustainability of humoral and cellular immune responses to RZV in ARD patients. No new patients will be recruited, nor will any new intervations be performed. ARD patients previously included in the study and non-immunosuppressed control subjects who received both vaccine doses and collected samples for immunogenicity 6 weeks and one year after the second dose will be part of the proposed extension. A total of 1,025 ARD patients enrolled and 365 healthy controls will be included in the long-term follow-up phase. Considering a conservative 10% dropout, the final patient sample will be approximately 1,000. Ethical statement: The extension protocol was approved by the institutional Ethics Committee (report 7.988.896), and written consent will be obtained from all participants prior to inclusion. Humoral immunogenicity will be evaluated by analyzing the serum concentrations of anti-gE antibodies (ELISA) of blood samples collected from participants at 5-year after complete VZR vaccination, as previously described (Cunningham et al., 2018). Cellular immunogenicity will be evaluated in a convenience sample (20% of the total research participants) of patients with ARDs and healthy controls at 5-year after complete VZR vaccination. Vaccine efficacy will be evaluated by incident cases of HZ in the period of 5 years after RZV vaccination. Participants will be followed for 5 years after the second RZV dose through monthly contacts and routine clinical visits every 3-6 months.

Who can participate

Age range

18 Years – 75 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * All subjects will be adults (≥18 years-old). * ARD patients will be selected from patients regularly followed up at the Outpatient Rheumatology Clinics of the Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil, according to the specific classification criteria: RA (Aletaha et al., 2010), SLE (Petri et al., 2012), pSS (Vitali et al., 2002), SSc (van den Hoogen et al., 2013), IIM (Lundberg et al., 2017), axial spondyloarthritis (axSpA) (Rudwaleit et al., 2009), PsA (Tillett et al., 2012) and granulomatosis with polyangiitis (Leavitt et al., 1990). * Patients must be under current use of cyclophosphamide, mycophenolate mofetil, azathioprine, cyclosporin, tacrolimus, leflunomide, glucocorticoids, methotrexate, biologic therapy or JAKi with or without csDMARDs for at least one month prior to study inclusion. Exclusion Criteria: * history of any reaction or hypersensitivity to any component of the vaccine; * previous HZ vaccination; * any occurrence of Guillain-Barré syndrome; * hospitalization, acute infectious disease or fever at the time of vaccination; * pregnancy or lactation at the time of vaccination; * history of HZ within the 12 months preceding the first dose of study vaccine; * people living with HIV/AIDS (PLWHA).

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this is a Phase 4 trial studying the recombinant herpes zoster vaccine in people with my specific condition, can you tell me whether the early data suggests the vaccine is causing disease flares in patients with autoimmune rheumatic diseases like mine?
2This trial is comparing vaccinated patients to a placebo group to track disease flares — given my current disease activity level, how would you assess my personal risk of a flare if I were to receive the shingles vaccine outside of a trial?
3One part of this study looks at whether temporarily stopping methotrexate or mycophenolate mofetil affects how well the vaccine works — if I'm on either of those medications, would pausing them to improve vaccine effectiveness be a reasonable option for me, and what risks would that carry?
4Since this trial is no longer actively recruiting, is there another way I could access the recombinant herpes zoster vaccine, and would you recommend it for me given my diagnosis and current immunosuppressive treatment?
5Are there any findings from this study already available that would help us decide whether vaccinating me now is safer than waiting, especially compared to the known risk of shingles that comes with being on immunosuppressive therapy?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Subproject A: Disease safety (flare) in ARD patients immunized with RZV in comparison to non-vaccinated ARD patients (placebo group)

Timeframe: Six months

Subproject B: Effect of MTX discontinuation on immunogenicity in comparison to MTX maintenance

Timeframe: One year

Subproject B: Effect of MMF discontinuation on immunogenicity in comparison to MMF maintenance

Timeframe: One year

Trial details

NCT IDNCT05879419

SponsorUniversity of Sao Paulo General Hospital

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-12-01

View on ClinicalTrials.gov More Rheumatoid Arthritis trials

Plain-language summary

Who can participate

Age range

18 Years – 75 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

What they're measuring

Subproject A: Disease safety (flare) in ARD patients immunized with RZV in comparison to non-vaccinated ARD patients (placebo group)

Timeframe: Six months

Subproject B: Effect of MTX discontinuation on immunogenicity in comparison to MTX maintenance

Timeframe: One year

Subproject B: Effect of MMF discontinuation on immunogenicity in comparison to MMF maintenance

Timeframe: One year