Simultaneous RZV and aIIV4 Vaccination

Safety of Simultaneous Vaccination With Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Inactivated Influenza Vaccine (aIIV4)

The overall aim of the study is to compare the safety of simultaneous Zoster Vaccine Recombinant, Adjuvanted (RZV) (SHINGRIX®) and Quadrivalent Influenza Vaccine, Adjuvanted (FLUAD®) versus simultaneous Zoster Vaccine Recombinant, Adjuvanted (RZV) (SHINGRIX®) and Fluzone® High-Dose Quadrivalent vaccine in persons age ≥65 years. A prospective, randomized, blinded clinical trial that will be conducted during the 2021/2022 and 2022/2023 influenza seasons. Over the course of these two influenza seasons, approximately 220 older adults will be enrolled at Duke University Medical Center, and 180 older adults at Johns Hopkins University Medical Center. Eligible subjects will be randomized to receive either simultaneous RZV/FLUAD® or RZV/Fluzone® High-Dose vaccines. All subjects will be assessed for 7 days post-injection and safety and tolerability compared between the two groups. Serious adverse events and adverse events of clinical interest will be assessed 42 days post-vaccination and compared between the two groups. Health-related quality of life will be assessed pre-vaccination Day 1 through Day 8. Serious Adverse Events and Adverse Events of Clinical Interest were also assessed throughout the study period.

Study Overview

• Status: Completed
• Conditions: Quality of Life; Pain; Adverse Drug Event; Injection Site Reaction
• Intervention / Treatment: Biological: FLUAD® Quadrivalent; Biological: SHINGRIX®; Biological: Fluzone® High-Dose Quadrivalent

Detailed Description

Intention-to-Treat (ITT) Population: Defined as all subjects who are randomized and vaccinated.

Modified Intention-to-Treat (mITT) Population: Defined as all subjects who are randomized, vaccinated, and provide at least one day of complete data on the symptom diary.

• Study Type: Interventional
• Enrollment (Actual): 267
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21218
      • Johns Hopkins University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Male or female age ≥ 65 years
2. Intention of receiving IIV and RZV based on ACIP-CDC guidelines
3. Able to speak English
4. Willing to provide written informed consent
5. Living in the community
6. Intention of being available for entire study period and complete all relevant study procedures, including follow-up phone calls and clinic visits.
7. If HIV positive, HIV should be clinically stable.

Exclusion Criteria:

1. IIV or recombinant influenza vaccine (RIV) receipt during the respective 2021-2022 or 2022-2023 influenza season prior to study enrollment
2. Prior receipt of recombinant zoster vaccine (SHINGRIX®)

3. For non-COVID-19 Vaccines:

   • Receipt of any inactivated vaccine within 2 weeks prior to enrollment in this study
   • Receipt of any live vaccine within 4 weeks prior to enrollment in this study
   • Planning receipt of any non-COVID-19 vaccine during the entire period

4. For COVID-19 Vaccines:

   • Receipt of COVID-19 vaccine within 2 weeks prior to enrollment in this study. For those who have initiated a COVID-19 vaccine series, enrollment is not allowed until 2 weeks after the final dose of a COVID-19 vaccine is completed.
   • Planning receipt of a COVID-19 vaccine within 2 weeks after administration of study influenza and first dose recombinant zoster study vaccines.
5. Have acute illness or exacerbation of chronic illness within 72 hours of study vaccination
6. Hospitalization within the last 30 days for any reason
7. History of febrile illness (> 100.0°F or 37.8°C) within the past 24 hours prior to IIV administration
8. Has immunosuppression as a result of an underlying illness or treatment, or use of chemotherapy or radiation therapy within the preceding 12 months
9. Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) *Participants with a history of malignancy may be included if, after previous treatment by surgical excision, chemotherapy or radiation therapy, the participant has been observed for a period that in the investigator's estimation provides a reasonable assurance of sustained cure
10. A history of autoimmune disease, that requires immunosuppressive agents or any other chronic medical condition considered clinically significant by the investigator
11. Use of chronic oral or intravenous administration (≥14 days) of immunosuppressive doses of steroids, i.e., prednisone >10 mg per day, immunosuppressants or other immune-modifying drugs within 30 days of starting this study. (Use of topical, nasal, or inhaled steroids is permitted)
12. Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection (a daily aspirin may be acceptable)
13. Contraindication to IIV receipt including history of severe allergic reaction after a previous dose of any influenza vaccine; or to a vaccine component, including egg protein
14. Contraindication to RZV including history of a severe allergic reaction to any component of the RZV vaccine (including saponin or polysorbate 80) or to dose 2 of RZV
15. History of Guillain-Barré syndrome
16. History of Hepatitis C or active Hepatitis B
17. Receipt of blood or blood-derived products (including immunoglobulin) within 6 months prior to study vaccination
18. Dementia, any cognitive condition, or substance abuse that could interfere with study compliance
19. Anyone who is already enrolled or plans to enroll in another clinical trial with an investigational product within 28 days of vaccine receipt. Co-enrollment in observational or behavioral intervention studies are allowed at any time while enrollment in a clinical trial involving an investigational product (other than vaccine) may occur after 28 days following vaccine receipt
20. Any condition which, in the opinion of the investigators, may pose a health risk to the subject or interfere with the evaluation of the study objectives
21. Anyone who is a relative of any research study personnel
22. Anyone who is an employee of any research study personnel

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: Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Influenza Vaccine (FLUAD®); In this study arm, subjects will receive Dose 1 of RZV (SHINGRIX®) and Dose 1 of the adjuvanted influenza vaccine (FLUAD® Quadrivalent) simultaneously during Visit 1 and Dose 2 of RZV (SHINGRIX®) during Visit 6.	Biological: FLUAD® Quadrivalent; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Names: Influenza Vaccine, Adjuvanted (Quadrivalent); aIIV4; Biological: SHINGRIX®; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Names: Zoster Vaccine Recombinant, Adjuvanted (RZV)
Active Comparator: Zoster Vaccine Recombinant (RZV) and High-Dose Quadrivalent Influenza Vaccine (Fluzone®); In this study arm, subjects will receive Dose 1 of RZV (SHINGRIX®) and Dose 1 of the (Fluzone® HD Quadrivalent) influenza vaccine simultaneously during Visit 1 and Dose 2 of RZV (SHINGRIX®) during Visit 6.	Biological: SHINGRIX®; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Names: Zoster Vaccine Recombinant, Adjuvanted (RZV); Biological: Fluzone® High-Dose Quadrivalent; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Names: High-Dose Quadrivalent Influenza Vaccine; HD-IIV4

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Severe (Grade 3) Solicited Local or Systemic Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Local or Systemic Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group - Ages 65-69	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Local or Systemic Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group - Ages 70 and Older	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Severe (Grade 3) Solicited Local Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Local Reactogenicity Event After Dose 1 of RZV (SHINGRIX®)in Each Study Group - Ages 65-69	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Local Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group - Ages 70 and Older	Modified Intention-to-Treat (mITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Systemic Reactogenicity After Dose 1 of RZV (SHINGRIX®) in Each Study Group	Modified Intention-to-Treat (ITT) Population. Two subjects in the High-dose Quadrivalent Influenza arm reported local and systemic grade 3 events	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Systemic Reactogenicity After Dose 1 of RZV (SHINGRIX®) in Each Study Group - Ages 65-69	Modified Intention-to-Treat (ITT) Population. Two subjects in the High-dose Quadrivalent Influenza arm reported local and systemic grade 3 events	Up to 8 days post-vaccination
Number of Participants With at Least One Severe (Grade 3) Solicited Systemic Reactogenicity After Dose 1 of RZV (SHINGRIX®) in Each Study Group - Ages 70 and Older	Modified Intention-to-Treat (ITT) Population	Up to 8 days post-vaccination
Number of Participants With at Least One Adverse Event of Clinical Interest After Dose 1 of RZV (SHINGRIX®) in Each Study Group	Intention-to-Treat (ITT) Population	Up 43 days post-vaccination
Number of Participants With at Least One Serious Adverse Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group	Intention-to-Treat (ITT) Population	Up 43 days post-vaccination

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: Johns Hopkins University; Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Kenneth Schmader, MD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2021
• Primary Completion (Actual): March 4, 2023
• Study Completion (Actual): June 8, 2023

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: June 28, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: quality of life; influenza vaccine; fever following vaccination; pain following vaccination; Zoster Vaccine Recombinant, Adjuvanted (RSV) (SHINGRIX®); Quadrivalent Influenza Vaccine, Adjuvanted (FLUAD®); Fluzone(®) High-Dose Quadrivalent
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Pathologic Processes; Extravasation of Diagnostic and Therapeutic Materials; Drug-Related Side Effects and Adverse Reactions; Injection Site Reaction; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: Pro00108456

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes