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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Immunomodulator Monotherapy | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Recombinant Zoster Vaccine (RZV) | Biological | 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. |
| 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. |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Eloisa Bonfa, Full Professor | Contact | +55 11 3061-7492 | 7492 | eloisa.bonfa@hc.fm.usp.br |
| Clovis Silva, Full Professor | Contact | +55 11 3061-7492 | 7492 | clovisaasilva@gmail.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital das Clínicas | Recruiting | São Paulo | São Paulo | 05403-010 | Brazil |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37108130 | Background | 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. | |
| 30707761 |
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| ID | Term |
|---|---|
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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|
| 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. |
| 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. |
| 31399377 | Background | 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. |
| 34508560 | Background | 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. |
| 26990731 | Background | 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. |
| 38543908 | Background | 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. |
| 37438402 | Background | 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. |