Clinical trial NCT05007041: Simultaneous RZV and aIIV4 Vaccination
Official title: Safety of Simultaneous Vaccination With Zoster Vaccine Recombinant (RZV) and Quadrivalent Adjuvanted Inactivated Influenza Vaccine (aIIV4)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pain
Quality of Life
Injection Site Reaction
Adverse Drug Event
Keywords: influenza vaccine
fever following vaccination
pain following vaccination
quality of life
Zoster Vaccine Recombinant, Adjuvanted (RSV) (SHINGRIX®)
Quadrivalent Influenza Vaccine, Adjuvanted (FLUAD®)
Fluzone(®) High-Dose Quadrivalent
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Centers for Disease Control and Prevention
name: Johns Hopkins University
First posted: 2021-08-16
Enrollment: 267
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
Secondary outcomes:
measure: Number of Participants With at Least One Severe (Grade 3) Solicited Local Reactogenicity Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: Number of Participants With at Least One Severe (Grade 3) Solicited Systemic Reactogenicity After Dose 1 of RZV (SHINGRIX®) in Each Study Group
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: 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
timeFrame: Up to 8 days post-vaccination
measure: Number of Participants With at Least One Adverse Event of Clinical Interest After Dose 1 of RZV (SHINGRIX®) in Each Study Group
timeFrame: Up 43 days post-vaccination
measure: Number of Participants With at Least One Serious Adverse Event After Dose 1 of RZV (SHINGRIX®) in Each Study Group
timeFrame: Up 43 days post-vaccination
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Kenneth Schmader, MD
role: PRINCIPAL_INVESTIGATOR
References: