Shingrix in Patients With Rheumatic Diseases: a Double-blind Placebo-controlled RCT

Safety and Immunogenicity of a Recombinant Subunit Herpes Zoster Vaccine in Patients With Rheumatic Diseases Undergoing Immunosuppressive or Biologic/Targeted DMARD Therapies: a Double-blind Randomized Placebo-controlled Trial

A double-blind randomized controlled trial on the safety and immunogenicity of the recombinant subunit herpes zoster vaccine, Shingrix, in patients with rheumatic diseases undergoing immunosuppressive or biologic/targeted DMARD therapies

Study Overview

• Status: Not yet recruiting
• Conditions: Herpes Zoster
• Intervention / Treatment: Biological: recombinant subunit herpes zoster vaccine

Detailed Description

A double-blind randomized controlled trial on the safety and immunogenicity of the recombinant subunit herpes zoster vaccine, Shingrix, in patients with rheumatic diseases undergoing immunosuppressive or biologic/targeted DMARD therapies.

Duration of study: 60 weeks

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Chi Chiu Mok, MD, FRCP; Phone Number: 852-37677518; Email: ccmok2006@gmail.com
• Study Contact Backup: Name: Becky Fong; Phone Number: 852-24685111; Email: becky_fongls@yahoo.com.hk

Study Locations

• China
  • Hong Kong, China
    • Department of Medicine, Tuen Mun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria for patients:

1. Patients with a diagnosis of rheumatic or immune-mediated diseases eg. SLE, RA, PSA, SpA, inflammatory myopathies, ANCA-related and large vessel vasculitides
2. Age ≥18 years

3. Stable or reducing doses of any the following immunosuppressive regimens within 4 weeks of study entry:

   1. Prednisolone ≥20mg/kg/day ± mycophenolate mofetil, azathioprine or the calcineurin inhibitors
   2. Cyclophosphamide (intravenous pulses or daily oral)
   3. B-cell depleting biological agents and their biosimilars eg. belimumab, anti-CD20 agents (next scheduled dose should be arranged to at least 12 weeks after study entry for rituximab or obinutuzumab)
   4. Anti-TNFα biological agents and their biosimilars eg. infliximab, etanercept, adalimumab, golimumab, certolizumab
   5. Anti-interleukin-6 biological agents eg. tocilizumab, sarilumab
   6. Other biological agents eg. abatacept, ustekinumab, secukinumab, ixekizumab
   7. The JAK inhibitors eg. tofacitinib, baricitinib, upadacitinib
4. Female patients with reproductive potential are allowed to participate in this study provided that they are willing to practice contraception for until at least 12 months after vaccination
5. Willing to comply with all study procedures

Exclusion criteria for patients:

1. Active infection, including upper respiratory tract infection
2. Active HZ infection
3. Active untreated tuberculosis
4. HIV infection
5. History of HZ or varicella vaccination in the past
6. History of allergy to any vaccines
7. Patients who are pregnant or plan to become pregnancy within one year of study entry
8. Lactating women
9. Patients who cannot give a written consent (mentally incapable or illiterate)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: vaccine; Shingrix vaccine	Biological: recombinant subunit herpes zoster vaccine; vaccine administration; Other Names: Shingrix
Placebo Comparator: placebo; normal saline injection (0.5mL)	Biological: recombinant subunit herpes zoster vaccine; vaccine administration; Other Names: Shingrix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
humoral immune response to Shingrix	proportion of patients with 4x fold increase in anti-gE antibody titer	week 12 (compared with baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Humoral immune response	proportion of patients with 4x fold increase in anti-gE antibody titer	week 52
adverse events	solicited	7 days after injection
adverse events	unsolicited	4 weeks after injection
flares of underlying diseases	disease flares	week 26 and 60
herpes zoster infection	herpes zoster infection	week 60
cell mediated response to vaccine	in 40 patients (20 from each arm); number of IFNγ-secreting CD4+ T cell colonies on ELISPOT assay	week 12 from baseline

Collaborators and Investigators

• Sponsor: Tuen Mun Hospital
• Investigators: Principal Investigator: Chi Chiu Mok, Tuen Mun Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): January 1, 2026

Study Registration Dates

• First Submitted: February 7, 2021
• First Submitted That Met QC Criteria: February 8, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 8, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: immunosuppressive; vaccine; immunogenicity; rheumatic diseases; biologics; targeted DMARDs
• Additional Relevant MeSH Terms: Virus Diseases; Infections; Musculoskeletal Diseases; Connective Tissue Diseases; DNA Virus Infections; Herpesviridae Infections; Varicella Zoster Virus Infection; Rheumatic Diseases; Collagen Diseases; Herpes Zoster
• Other Study ID Numbers: NTWCShingrixstudy

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
• product manufactured in and exported from the U.S.: No