FLUAD® vs. Fluzone® High-Dose Study

NCT03183908 | Completed Phase 4 Results FDA Drug

• 1 other identifier: Pro00083845
• Study Type: interventional
• Target: 757
• Locations: 1 country
• Sites: 4

Brief Summary

The overall aim of the study is to compare safety and immunogenicity of inactivated influenza vaccine (IIV), adjuvanted (FLUAD®) versus High-Dose inactivated influenza (Fluzone® High-Dose) vaccine in persons ≥65 years (20% aged ≥80 years). A prospective, randomized, blinded clinical trial that will be conducted during the 2017/2018 and 2018/2019 influenza seasons. During each season, approximately 220 older adults will be enrolled at Duke University Medical Center and 140 older adults at Boston University Medical Center. Eligible subjects will be randomized to receive either adjuvanted influenza vaccine or High-Dose influenza vaccine. All subjects will receive vaccine and provide a blood draw at Visit 1, and then return for a second blood draw without vaccination about 4 weeks later to assess for influenza antibody titers. A subset of 100 subjects at Duke will provide a third blood draw 6 months post-vaccination to assess for waning of influenza antibody titers. Subjects will record the occurrence of local and systemic reactions (including fever, pain, tenderness, swelling, redness, general systemic systems), unsolicited adverse events, medical care utilization, and changes in medications over 8 days following vaccination. In addition, serious adverse events and events of clinical interest will be assessed through 42 days post-vaccination. Health-related quality of life will be assessed pre-vaccination (Day 1) and on Days 3 and 9 post-vaccination.

Conditions

Pain; Quality of Life; Injection Site Reaction; Side Effect of Drug; Adverse Drug Event

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Injection-Site Pain in Arm That Was Vaccinated, Population 1

  Comparison of the proportion of subjects reporting moderate/severe injection site pain within the first week post-vaccination in both treatment groups.

  Days 1 through 8 post-vaccination

• Number of Participants With Adverse Events of Clinical Interest, Population 2

  The frequency and descriptions of adverse events of clinical interest observed in the two treatment groups.

  42 days post-vaccination and compared between the two groups.

• Observed Serious Adverse Events in Both Treatment Groups, Population 2

  The frequency and descriptions of serious adverse events observed in the two treatment groups. No analytical analysis was completed.

  42 days post-vaccination and compared between the two groups.

• Number of Participants With H3N2 HAI Seroconversion

  H3N2 hemagglutination inhibition assay (HAI) seroconversion: The proportion of subjects achieving H3N2 seroconversion at day 29 (an HAI titer \> 1:40 at day 29 if the baseline titer is \< 1:10 or a four-fold rise in HAI titer if the baseline titer is \> 1:10) in the respective season's vaccine

  29 days post-vaccination

Secondary Outcomes (24)

• Number of Participants With Local Reactions in Arm That Was Vaccinated - Full Study, Population 1

  Days 1 through 8 post-vaccination

• Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 65 - 79, Population 1

  Days 1 through 8 post-vaccination

• Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 80 +, Population 1

  Days 1 through 8 post-vaccination

• Number of Participants With Systemic Reactions - Full Study Population, Population 1

  Days 1 through 8 post-vaccination

• Number of Participants With System Reactions - Ages 65 - 79, Population 1

  Days 1 through 8 post-vaccination

Study Arms (2)

Adjuvanted influenza vaccine (FLUAD®)

ACTIVE COMPARATOR

In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1.

Biological: FLUAD®

High-dose influenza vaccine (Fluzone® HD)

ACTIVE COMPARATOR

In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1.

Biological: Fluzone® High-Dose

Interventions

FLUAD® BIOLOGICAL

Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine

Also known as: Adjuvanted influenza vaccine

Adjuvanted influenza vaccine (FLUAD®)

Fluzone® High-Dose BIOLOGICAL

Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine

Also known as: High-dose influenza vaccine

High-dose influenza vaccine (Fluzone® HD)

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Persons aged ≥65 years, living in the community
• Intention of receiving IIV vaccine based on ACIP-CDC guidelines
• Willing to provide written informed consent prior to initiation of any study procedures
• Able to speak English
• Able and willing to complete baseline assessments and questionnaires, and to allow information to be collected from their electronic medical record
• Able and willing to complete post-vaccine assessments and questionnaires independently or with assistance
• Able and willing to have blood drawn for the study
• Able and willing to return in about one month for a follow-up visit including completing questionnaires and having another blood test
• Access to and ability to use a phone, independently or with assistance
• Adequate vision and motor skills to complete the diary form independently or with assistance.
• Not living in a skilled nursing facility/nursing home/long term acute care facility

You may not qualify if:

• IIV receipt during the current influenza season prior to study enrollment
• Enrolled in this study during the 2017-18 (Year 1) influenza season
• Note: Year 1 study participants will only be enrolled in Year 2 if they are participating in the sub-study on repeat vaccination
• Has immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 12 months.
• Has an active neoplastic disease (excluding non-melanoma skin cancer or prostate cancer that is stable in the absence of therapy) or a history of any hematologic malignancy\*
• \*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 (not less than 12 months)
• Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection
• History of febrile illness (\> 100.0°F or 37.8°C) within the past 24 hours prior to IIV administration (temporary deferral)
• 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; or a latex allergy
• \*Formaldehyde, Octylphenol ethoxylate, neomycin, kanamycin, barium, cetyltrimethlyammonium bromide (CTAB)
• Any history of Guillain-Barré syndrome
• Mild to severe dementia as determined by the Mini-Cog tool and the Rowland Universal Dementia Assessment Scale (RUDAS)
• Substance use that could interfere with study compliance
• Receipt of any inactivated licensed vaccine within 2 weeks, or live attenuated licensed vaccine within 4 weeks prior to enrollment in this study, or planning receipt of any vaccines during the 42-days post-vaccination period (including pneumococcal vaccines)
• 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 30 days following vaccine receipt.

Sponsors & Collaborators

• Duke University: lead
• Centers for Disease Control and Prevention: collaborator
• Boston Medical Center: collaborator
• Children's Hospital Medical Center, Cincinnati: collaborator

Study Sites (4)

Centers for Disease Control and Prevention

Atlanta, Georgia, 30333, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (2)

• Schmader KE, Liu CK, Flannery B, Rountree W, Auerbach H, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Harrington T, Li R, Broder KR, Walter EB. Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial. Immun Ageing. 2023 Jul 1;20(1):30. doi: 10.1186/s12979-023-00355-7.

  PMID: 37393237 DERIVED

• Schmader KE, Liu CK, Harrington T, Rountree W, Auerbach H, Walter EB, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Wodi P, Broder KR. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2031266. doi: 10.1001/jamanetworkopen.2020.31266.

  PMID: 33443580 DERIVED

MeSH Terms

Conditions

Pain; Injection Site Reaction; Drug-Related Side Effects and Adverse Reactions; Influenza, Human

Interventions

fluad vaccine; Influenza Vaccines

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Extravasation of Diagnostic and Therapeutic Materials; Pathologic Processes; Chemically-Induced Disorders; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Kenneth Schmader
• Organization: Duke University

kenneth.schmader@duke.edu

919-660-7572

Study Officials

• Kenneth Schmader, MD

  Duke University

  PRINCIPAL INVESTIGATOR

• Theresa Harrington, MD

  Centers for Disease Control and Prevention

  PRINCIPAL INVESTIGATOR

• Elizabeth Barnett, MD

  Boston University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Subject, study coordinators, and investigators will be blinded to the type of flu vaccine administered. Only the vaccinator will be unblinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 12, 2017
• Study Start: August 28, 2017
• Primary Completion: February 14, 2019
• Study Completion: February 14, 2019
• Last Updated: March 30, 2021
• Results First Posted: March 30, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)