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

Official title

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

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.

Interventions

• 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.

Primary outcome measures

• Seroconversion rate of anti-glycoprotein E (anti-gE) antibodies six weeks after completion of the RZV vaccination schedule [Time frame: Baseline (Day 1) through day 84.]

Secondary outcome measures (8)

• Geometric mean titers of anti-glycoprotein E antibodies six weeks after completion of the RZV vaccination schedule [Time frame: Baseline (Day 1) through day 84.]
• Persistence of antibody titers one year after completion of the RZV vaccination scheme [Time frame: Day 1 (baseline) through day 84 and one year after the second dose (Day 365)]
• Safety of RZV vaccine in ARD patients under immunomodulators [Time frame: Baseline (Day 1) through day 84.]
• Incidence of herpes zoster over one year following RZV vaccination in ARD patients under immunomodulators therapy [Time frame: Day 42 through one year after the second dose (D365).]
• Disease safety (flare) - Rheumatoid Arthritis [Time frame: Day 1 (baseline) through day 42 and six weeks after the second dose D84.]
• Disease safety (flare) - Systemic Lupus Erythematosus [Time frame: Day 1 (baseline) through day 42 and six weeks after the second dose D84.]
• Disease safety (flare) - Ankylosing Spondylitis [Time frame: Day 1 (baseline) through day 42 and six weeks after the second dose D84.]
• Disease safety (flare) - Sjögren's Syndrome [Time frame: Day 1 (baseline) through day 42 and six weeks after the second dose D84.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Prevention

Study locations

Brazil · 1 center

• Hospital das Clínicas — São Paulo

Publications

• 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. PMID 37108130
• 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 PMID 30707761
• 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 PMID 31399377
• 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. PMID 34508560
• 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. PMID 26990731
• 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. PMID 38543908
• 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. PMID 37438402

Identifiers

NCT: NCT07280741 · 94187625300000068

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗