Recombinant Zoster Vaccine in Stable SLE Patients

Efficacy and Safety of Recombinant Zoster Vaccine in Stable SLE Patients(Vtrial)

The risk of herpers zoster reactivation is higher in SLE patients than general population. It has shown that mild or even inactive patients could also have varicella zoster virus (VZV) infections, and they account for about two-thirds of the events. And our previous study indicated that recent various VZV infection was associated with increased risk of disease flares. The risk of virus reactivation limited the use of live-attenuated shingles vaccine in SLE patients, especially in whom with high dose of prednisone or immunosuppressants. Whether the introduction of recombinant zoster vaccine could reduce the risk of zoster reactivation in lupus patients is to be explored in this study.

Study Overview

• Status: Recruiting
• Conditions: Systemic Lupus Erythematosus; Herpes Zoster; Recombinant Zoster Vaccine
• Intervention / Treatment: Biological: Recombinant zoster vaccine; Biological: Placebo

Detailed Description

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease that requires long-term corticosteroid and/or immunosuppressive agents. Thus lupus patients are immunocompromised patients, and the incidence of herpes zoster is higher than general population (asian population 32.5-91.4/1000 person-years vs general population 2.58-4.89/1000 person-years). Patients with active SLE are more susceptible because they require stronger immunosuppressive therapy. However, even mild or even stable lupus patients are highly susceptible, and they account for about two-thirds of the events. In addition, herpes zoster may trigger lupus flare. A case-control study showed a close correlation between herpes zoster reactivation and the diagnosis of lupus, and our previous studies indicated that recent VZV infection was associated with increased risk of disease flares. The risk of virus reactivation limited the use of live-attenuated shingles vaccine in SLE patients, especially in whom with high dose of prednisone or immunosuppressants. Whether the introduction of recombinant herpes zoster could reduce the risk of zoster reactivation in lupus patients is to be explored in this study.

• Study Type: Interventional
• Enrollment (Anticipated): 464
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fangfang Sun, MD.; Phone Number: 86 15800901145; Email: Fiona_rj@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Shuang Ye, MD
      • Contact: Huijing Wang, postgraduate; Phone Number: +8618267851823; Email: whj30813@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≥ 50 years old
2. The disease status is stable (score≤ 6 at screening on SELENA-SLEDAI); no British Isles Lupus Assessment Group (BILAG) A and no more than one BILAG B;
3. A stable treatment regimen with fixed doses of prednisone (≤ 20mg/day), antimalarial, or immunosuppressive drugs (azathioprine/mycophenolate mofetil/ methotrexate/ciclosporin/tacrolimus/leflunomide/belimumab);
4. Sign the informed consent.

Exclusion Criteria:

1. Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) > 2 times upper normal limits; creatinine clearance rate < 60ml/min;
2. Exposure to cyclophosphamide within the past half year.
3. Exposure to rituximab within the past one year.
4. History of herpes zoster within the past three months;
5. Pregnancy or lactation;
6. History of malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Recombinant zoster vaccine; Eligible patients were randomized in a 1:1 ratio to recombinant zoster vaccine/placebo on the background of standard of care (SOC). Participants received two intramuscular doses of the vaccine 2 months apart.	Biological: Recombinant zoster vaccine; Recombinant zoster vaccine (RZV) is indicated for prevention of herpes zoster in adults aged ≥ 50 years old. RZV contains a varicella zoster virus glycoprotein E antigen and the AS01B adjuvant system.
Placebo Comparator: Placebo; Eligible patients were randomized in a 1:1 ratio to recombinant zoster vaccine/placebo on the background of standard of care (SOC). Participants received two intramuscular doses of the placebo (sterilized water) 2 months apart.	Biological: Placebo; Sterilized water

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of participants with herpes zoster	The efficacy of recombinant zoster vaccine in stable systemic lupus patients	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Humoral immunity was measured as geometric mean concentrations (GMCs) of serum anti-gE antibodies (ELISA), and CMI was measured as the frequency of CD4 T cells expressing ≥ 2 of 4 selected activation markers (interferon-γ, interleukin-2, tumour necrosis factor-α and CD40 ligand) per 10^6 CD4 T cells after stimulation with gE peptides (hereafter referred to as CD4^2+ T cells)	Baseline, 3 month, and 12 month
Percent of participants with lupus flares	either minor/moderate flare or major flare defined by SLEDAI Flare Index	12 months
Change of interferon score during follow-up	Interferon score is detected at each visit, the time of herpes zoster and lupus flare.	12 months
Adverse events	To evaluate for adverse effects following immunization patients will submit the adverse effects by app tracking system.	12 months

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Fangfang Sun, MD., Renji Hospital, Shouth Campus

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): September 30, 2023

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2022
• Last Update Submitted That Met QC Criteria: October 25, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Virus Diseases; Infections; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Lupus Erythematosus, Systemic; Herpes Zoster
• Other Study ID Numbers: Vtrial

Drug and device information, study documents

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