Simultaneous RZV and aIIV4 Vaccination

• ClinicalTrials.gov Identifier: NCT05007041
• Recruitment Status: Suspended
• First Posted: August 16, 2021
• Last Update Posted: June 7, 2022
• Sponsor: Duke University
• Collaborators: Centers for Disease Control and Prevention; Johns Hopkins University
• Information provided by (Responsible Party): Duke University

Study Description

Brief Summary:

The overall aim of the study is to compare the safety of simultaneous RZV (SHINGRIX®) and inactivated adjuvanted influenza vaccine aIIV4 (FLUAD®) versus simultaneous RZV (SHINGRIX®) and inactivated influenza HD-IIV4 (Fluzone® HD) vaccine in persons ≥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/aIIV4 or RZV/HD-IIV4 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.

Condition or disease	Intervention/treatment	Phase
Pain; Quality of Life; Injection Site Reaction; Adverse Drug Event	Biological: FLUAD® Quadrivalent; Biological: Fluzone® HD Quadrivalent; Biological: SHINGRIX®	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 400 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Subjects, study coordinators, and investigators will be blinded to the type of flu vaccine administered in conjunction with the Shingrix vaccine.
• Primary Purpose: Prevention
• Official Title: Safety of Simultaneous Vaccination With Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Inactivated Influenza Vaccine (aIIV4)
• Actual Study Start Date: September 21, 2021
• Estimated Primary Completion Date: March 8, 2023
• Estimated Study Completion Date: April 12, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Recombinant Zoster Vaccine (RZV) and Quadrivalent adjuvanted influenza vaccine; In this study arm, subjects will receive Dose 1 of RZV (SHINGRIX®) and Dose 1 of the quadrivalent 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 Name: Influenza Vaccine, Adjuvanted (Quadrivalent); Biological: SHINGRIX®; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Name: Zoster vaccine recombinant, adjuvanted
Active Comparator: Recombinant Zoster Vaccine (RZV) and high-dose quadrivalent influenza vaccine; 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: Fluzone® HD Quadrivalent; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Name: High-dose quadrivalent influenza vaccine; Biological: SHINGRIX®; Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine; Other Name: Zoster vaccine recombinant, adjuvanted

Outcome Measures

Primary Outcome Measures :

1. Number of participants with at least one severe (Grade 3) solicited local or systemic reactogenicity event after SHINGRIX® dose 1 in each study group [ Time Frame: Up to 8 days post-vaccination ]
   Modified Intention-to-Treat (mITT) Population

Secondary Outcome Measures :

1. Number of participants with at least one severe (Grade 3) solicited local reactogenicity event after SHINGRIX® dose 1 in each study group [ Time Frame: Up to 8 days post-vaccination ]
   Modified Intention-to-Treat (mITT) Population
2. Number of participants with at least one severe (Grade 3) solicited systemic reactogenicity after SHINGRIX® dose 1 in each study group [ Time Frame: Up to 8 days post-vaccination ]
   Modified Intention-to-Treat (ITT) Population
3. Number of participants with at least one serious adverse event or adverse event of clinical interest after SHINGRIX® dose 1 in each study group [ Time Frame: Up 42 days post-vaccination ]
   Intention-to-Treat (ITT) Population

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, North Carolina

Duke University

Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Centers for Disease Control and Prevention

Johns Hopkins University

Investigators

• Principal Investigator: Kenneth Schmader, MD; Duke University

More Information

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT05007041
• Other Study ID Numbers: Pro00108456
• First Posted: August 16, 2021
• Last Update Posted: June 7, 2022
• Last Verified: June 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Duke University:

influenza vaccine; Shingrix vaccine; fever following vaccination; pain following vaccination; quality of life

Additional relevant MeSH terms:

Injection Site Reaction; Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Extravasation of Diagnostic and Therapeutic Materials; Pathologic Processes; Vaccines; Immunologic Factors; Physiological Effects of Drugs