Recombinant Herpes Zoster Vaccine in Patients With Autoimmune Rheumatic Diseases Under Immunomodulators (IMUNO-RZV)

Efficacy, Immunogenicity, and Safety of the Recombinant Herpes Zoster Vaccine (RZV) in Patients With Autoimmune Rheumatic Diseases Under Immunomodulators

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 Overview

• Status: Recruiting
• Conditions: Autoimmune Rheumatic Diseases
• Intervention / Treatment: Biological: Recombinant Zoster Vaccine (RZV)

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Eloisa Bonfa, Full Professor; Phone Number: 7492 +55 11 3061-7492; Email: eloisa.bonfa@hc.fm.usp.br
• Study Contact Backup: Name: Clovis Silva, Full Professor; Phone Number: 7492 +55 11 3061-7492; Email: clovisaasilva@gmail.com

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403-010
      • Recruiting
      • Hospital das Clinicas
      • Contact: Humberto Clemente; Phone Number: 55 11 30617490; Email: Humbertoclemente32@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immunomodulator Monotherapy; Participants with autoimmune rheumatic diseases who are clinically stable and receiving monotherapy with hydroxychloroquine or sulfasalazine will receive two doses of the recombinant zoster vaccine (RZV, Shingrix) administered intramuscularly on Day 0 and Day 42. Immunogenicity will be evaluated through anti-glycoprotein E antibody titers at baseline, six weeks, and one year after vaccination. Safety, disease activity, and incidence of herpes zoster will be monitored throughout follow-up.

Biological: Recombinant Zoster Vaccine (RZV); VRZ (Shingrix®) is composed of 50 μg of recombinant VZV glycoprotein E (gE) and the liposome-based AS01B (HZ/su) adjuvant system (containing 50 μg of 3-O-desacyl-4'-monophosphoryl lipid A [MPL] and 50 μg of Quillaja saponaria Molina, fraction 21 (QS21), licensed by GSK from Antigenics, a subsidiary of Agenus). Two doses of the vaccine will be administered (0.5 mL) into the deltoid muscle on days (D) 0 and D42.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) through day 84.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1) through 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.	Day 1 (baseline) through 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.	Baseline (Day 1) through day 84.
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.	Day 42 through one year after the second dose (D365).
Disease safety (flare) - Rheumatoid Arthritis	Rheumatoid Arthritis (RA): An absolute increase in Disease Activity Score C-reactive protein (DAS28-CRP) > 1.2, or an increase > 0.6 if baseline > 3.2. Score: 0 to 10 - higher values indicates higher disease activity.	Day 1 (baseline) through day 42 and six weeks after the second dose D84.
Disease safety (flare) - Systemic Lupus Erythematosus	Systemic Lupus Erythematosus (SLE): An increase of more than three points in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Score: 0 - No activity; 1 - 4 mild activity; > 6 high activity	Day 1 (baseline) through day 42 and six weeks after the second dose D84.
Disease safety (flare) - Ankylosing Spondylitis	Ankylosing Spondylitis (AS): An increase in Ankylosing Spondylitis Disease Activity Score (ASDAS). Scores activity: <1.3: Inactive disease 1.3 to <2.1: Moderate disease activity 2.1 to 3.5: High disease activity >3.5: Very high disease activity	Day 1 (baseline) through day 42 and six weeks after the second dose D84.
Disease safety (flare) - Sjögren's Syndrome	We will use the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). This score ranges from 0 (minimum) to 123 (maximum). Higher scores indicates greater disease activity.	Day 1 (baseline) through day 42 and six weeks after the second dose D84.

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Publications and helpful links

General Publications

• Yun H, Yang S, Chen L, Xie F, Winthrop K, Baddley JW, Saag KG, Singh J, Curtis JR. Risk of Herpes Zoster in Autoimmune and Inflammatory Diseases: Implications for Vaccination. Arthritis Rheumatol. 2016 Sep;68(9):2328-37. doi: 10.1002/art.39670.
• Dagnew AF, Ilhan O, Lee WS, Woszczyk D, Kwak JY, Bowcock S, Sohn SK, Rodriguez Macias G, Chiou TJ, Quiel D, Aoun M, Navarro Matilla MB, de la Serna J, Milliken S, Murphy J, McNeil SA, Salaun B, Di Paolo E, Campora L, Lopez-Fauqued M, El Idrissi M, Schuind A, Heineman TC, Van den Steen P, Oostvogels L; Zoster-039 study group. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in adults with haematological malignancies: a phase 3, randomised, clinical trial and post-hoc efficacy analysis. Lancet Infect Dis. 2019 Sep;19(9):988-1000. doi: 10.1016/S1473-3099(19)30163-X. Epub 2019 Aug 6.
• Vink P, Delgado Mingorance I, Maximiano Alonso C, Rubio-Viqueira B, Jung KH, Rodriguez Moreno JF, Grande E, Marrupe Gonzalez D, Lowndes S, Puente J, Kristeleit H, Farrugia D, McNeil SA, Campora L, Di Paolo E, El Idrissi M, Godeaux O, Lopez-Fauqued M, Salaun B, Heineman TC, Oostvogels L; Zoster-028 Study Group. Immunogenicity and safety of the adjuvanted recombinant zoster vaccine in patients with solid tumors, vaccinated before or during chemotherapy: A randomized trial. Cancer. 2019 Apr 15;125(8):1301-1312. doi: 10.1002/cncr.31909. Epub 2019 Feb 1.
• Venerito V, Stefanizzi P, Cantarini L, Lavista M, Galeone MG, Di Lorenzo A, Iannone F, Tafuri S, Lopalco G. Immunogenicity and Safety of Adjuvanted Recombinant Zoster Vaccine in Rheumatoid Arthritis Patients on Anti-Cellular Biologic Agents or JAK Inhibitors: A Prospective Observational Study. Int J Mol Sci. 2023 Apr 9;24(8):6967. doi: 10.3390/ijms24086967.
• Qian J, Lassere MN, Heywood AE, Liu B. Use of disease-modifying antirheumatic drugs and the subsequent risk of herpes zoster in older adults. Rheumatology (Oxford). 2021 Nov 3;60(11):5042-5051. doi: 10.1093/rheumatology/keab538.
• Yap RXL, Lai YW, Wei C, Ng JJW, Xu D, Feng S, Mu R, Thong BY, Xu C. Impact of Immunomodulatory Therapy on COVID-19 Vaccine Response in Patients with Autoimmune Inflammatory Rheumatic Diseases. Vaccines (Basel). 2024 Mar 6;12(3):274. doi: 10.3390/vaccines12030274.
• van Sleen Y, van der Geest KSM, Huckriede ALW, van Baarle D, Brouwer E. Effect of DMARDs on the immunogenicity of vaccines. Nat Rev Rheumatol. 2023 Sep;19(9):560-575. doi: 10.1038/s41584-023-00992-8. Epub 2023 Jul 12.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2025
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): March 11, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Inflammation; Safety; Vaccine; Immunogenicity; Immunomodulators; Hepers Zoster
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Signs and Symptoms; Inflammation
• Other Study ID Numbers: 94187625300000068

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No