Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases Under Immunomodulators

Phase 4Not Yet RecruitingNCT07280741

University of Sao Paulo General Hospital200 enrolled

Overview

This interventional phase IV clinical trial will evaluate the efficacy, immunogenicity and safety of the adjuvanted recombinant herpes zoster vaccine (RZV) in adults with autoimmune rheumatic diseases (ARDs) receiving immunomodulatory monotherapy. Humoral immune response will be quantified by anti-glycoprotein E (anti-gE) antibody titers. Patients will receive two doses of RZV. Outcomes include seroconversion and geometric mean titers six weeks after completion of the vaccination schedule, persistence of antibody titers at one year, and incidence of confirmed herpes zoster during follow-up.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

200

Conditions

Autoimmune Rheumatic Diseases

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Adults aged 18 years or older. * Diagnosis of an autoimmune rheumatic disease (such as rheumatoid arthritis, systemic lupus erythematosus, axial spondyloarthritis, psoriatic arthritis, systemic sclerosis, Sjögren syndrome, idiopathic inflammatory myopathies, or primary systemic vasculitis) according to validated classification criteria. * Clinical stability at the time of enrollment, defined as no change in disease-modifying therapy or corticosteroid dose in the preceding four weeks and no evidence of infection or disease flare. * Current use of hydroxychloroquine or sulfasalazine in monotherapy for at least three months prior to inclusion. * Can be under prednisone use of 5mg/week. * Ability and willingness to comply with study procedures and follow-up visits. * Provision of written informed consent. Exclusion Criteria: * Previous vaccination with recombinant zoster vaccine (RZV). * History of herpes zoster or varicella infection within 12 months before enrollment. * Concomitant use of systemic immunosuppressive therapy including but not limited to methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide, biologics, or JAK inhibitors. * Use of glucocorticoids \>5mg/week. * Acute febrile illness or active infection at the time of vaccination. * Pregnancy or breastfeeding. * Known hypersensitivity to any component of the recombinant zoster vaccine. * History of Guillain-Barré syndrome. * Any condition that, in the investigators' judgment, could interfere with study participation or interpretation of results.

Outcomes

Primary Outcomes

Seroconversion rate of anti-glycoprotein E (anti-gE) antibodies six weeks after completion of the RZV vaccination schedule

Humoral response will be assessed by ELISA quantification of anti-glycoprotein E antibodies. Seroconversion will be defined as a fourfold or greater increase from baseline or a fourfold increase above the lower limit of quantification for participants who are seronegative at baseline. The outcome is the proportion of participants who achieve seroconversion at Day 84.

Time frame: Day 0 to six weeks after the second dose (Day 84)

Secondary Outcomes

Geometric mean titers of anti-glycoprotein E antibodies six weeks after completion of the RZV vaccination schedule

Anti-glycoprotein E antibody concentrations will be measured in serum samples using an ELISA. Titers will be log-transformed and geometric mean titers will be calculated as the exponential of the mean of the log-transformed values. The outcome is the GMT at Day 84 and its change relative to baseline.

Time frame: Baseline (Day 0) and six weeks after the second dose (Day 84)

Persistence of antibody titers one year after completion of the RZV vaccination scheme

Antibody persistence will be evaluated by quantifying anti-glycoprotein E antibody concentrations using ELISA. Results will be expressed as geometric mean titers obtained from log-transformed antibody levels. Seroconversion at one year will be defined as a fourfold or greater increase relative to baseline or a fourfold increase above the assay lower limit of quantification for participants seronegative at baseline.

Time frame: Day 0 to six weeks after the second dose (Day 84) and one year after the second dose (Day 365)

Safety of RZV vaccine in ARD patients under immunomodulators

Safety will be assessed by recording local and systemic adverse events through standardized diaries completed after each dose and confirmed during clinic visits. Events will be graded according to World Health Organization severity and CDC criteria.

Time frame: Day 0 to six weeks after the second dose (Day 84)

Disease safety (flare) in ARD patients immunized with RZV

Flare will be defined as a new flare or worsening of previous disease activity according to established scores for each ARD or the change of therapy. Disease activity will be evaluated in ARD patients according to specific standardized disease activity indexes: RA (DAS28 - Disease Activity Score 28, RA-CDAI - Rheumatoid Arthritis Clinical Disease Activity Index), SLE (SLEDAI2K - Systemic Lupus Erythematosus Disease Activity Index 2000), pSS (ESSDAI- EULAR Sjögren's Syndrome Disease Activity Index), IIM (MMT - Manual Muscle Test), AxS (ASDAS - Ankylosing Spondylitis Disease Activity Score), and vasculitis (Birmingham Vasculitis Activity Score).

Time frame: Day 0 to six weeks after the first dose (Day 42) and six weeks after the second dose (D84)

Incidence of herpes zoster over one year following RZV vaccination in ARD patients under immunomodulators therapy

A suspected case of herpes zoster will be defined as (1) a new unilateral, dermatomal, rash with pain (broadly defined to include allodynia, pruritus, or other abnormal sensations) without any alternative diagnosis or (2A) or a vesicular rash suggestive of varicella zoster virus infection regardless of the distribution, and no alternative diagnosis; without any alternative diagnosis. For each suspected case, the rash will be photographed and samples will be collected from three lesions to confirm the diagnosis of HZ by real-time polymerase-chain reaction (PCR) assay. If the PCR results were indeterminate or if samples were not available, the final diagnosis will be determined by unanimous agreement among the five members of an ascertainment committee, which includes a dermatologist.

Time frame: Day 42 (after the second dose) through one year after the second dose