Clinical trial NCT05047770: A Study on the Immune Response and Safety of the Shingles Vaccine and the Influenza Vaccine When Either is Given to Healthy Adults at the Same Time or Following a COVID-19 Booster Vaccine
Official title: A Phase III, Randomized, Open-label, Controlled, Multicenter Study to Evaluate the Immune Response and Safety of Both Herpes Zoster Subunit Vaccine in Healthy Adults Aged 50 Years and Older AND the Influenza Virus Vaccine in Healthy Adults Aged 18 Years and Older When Administered Sequentially or Coadministered With mRNA-1273 Booster Vaccination
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Herpes Zoster
Keywords: COVID-19
Shingles
Influenza
Booster vaccination
HZ/su vaccine
Recombinant Zoster vaccine
Flu D-QIV vaccine
mRNA-1273 vaccine
Safety
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2021-09-17
Enrollment: 2013
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study was to evaluate the immune response and safety of both GlaxoSmithKline Biologicals SA's (GSK's) herpes zoster (HZ) subunit (su) vaccine in healthy adults 50 years of age (YOA) and older and quadrivalent seasonal influenza (Flu D-QIV) vaccine in healthy adults 18 YOA and older, when administered sequentially or co-administered with Moderna's mRNA-1273 booster vaccination against COVID-19.


Eligibility criteria: Inclusion Criteria:

* Participants who in the opinion of the investigator, can and who will comply with the requirements of the protocol (e.g., completion of the eDiaries, return for follow-up visits).
* Written informed consent obtained from the participant prior to performance of any study-specific procedure.
* Age at study entry:

  * For HZ/su and mRNA-1273 booster cohort: A male or female aged 50 years or older at the time of randomization.
  * For Flu D-QIV and mRNA-1273 booster cohort: A male or female aged 18 years or older at the time of enrollment.
* Healthy participants or medically stable patients as established by medical history and clinical examination at screening. A stable medical condition is defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 3 months before enrolment.
* Participants who have a documented previous mRNA-1273 primary vaccination series completed (i.e., both doses) at least 6 months prior to first vaccination.
* Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, documented total hysterectomy, bilateral ovariectomy, or bilateral salpingectomy, or post-menopause.
* Female participants of childbearing potential may be enrolled in the study, if the participant:

  * Has practiced effective contraception for 1 month prior to study intervention administration, and
  * Has a negative pregnancy test on the day of study intervention administration, and
  * Has agreed to continue effective contraception during the study until 2 months after completion of the study vaccination series.

Exclusion Criteria:

Medical conditions

* Any clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study or might confound post-study intervention administration safety assessments (e.g., tattoos overlying either study intervention administration site).
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions, including a known history of severe allergic reaction (e.g., anaphylaxis) to any component of any of the study vaccines.
* Any history of Guillain-Barré syndrome.
* Any history of myocarditis or pericarditis.
* Acute or chronic clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by medical history or physical examination.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
* Hypersensitivity to latex.
* For HZ/su and mRNA-1273 booster cohort: history of Herpes Zoster.

Prior/concomitant therapy

* Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -29 to Day 1), or their planned use during the study period.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before first dose and ending 30 days after the last dose of study intervention administration. However, for HZ/su and mRNA-1273 booster cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., inactivated and subunit vaccines, including inactivated and subunit influenza vaccines, with or without adjuvant for seasonal or pandemic flu) may be administered up until 8 days prior to dose 1 of HZ/su and/or dose 2 of HZ/su and/or at least 14 days after any dose of HZ/su. For Flu D-QIV and mRNA-1273 booster cohort: licensed pneumococcal vaccines and non-replicating vaccines (i.e., inactivated and subunit vaccines, other than influenza vaccines) may be administered up until 8 days prior to dose 1 of Flu D-QIV and/or at least 30 days after any dose of Flu D-QIV. For time interval between other routine vaccines with mRNA-1273 booster dose (administered in the study), local guidelines must be followed.

In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced if necessary for that mass vaccination vaccine, provided this vaccine is licensed and used according to its Product Information.

* Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).
* Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the first dose of study intervention(s) up to 1 month post last dose or planned administration during the study period.
* Prior planned or chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine. For corticosteroids, this will mean more than 14 days in total of prednisone ≥20 mg/day or equivalent is not allowed. Inhaled, intra-articular and topical steroids are allowed.
* For HZ/su and mRNA-1273 booster cohort: Previous vaccination against Herpes Zoster with the exception of receipt of live attenuated HZ vaccine.
* For Flu D-QIV and mRNA-1273 booster cohort: Administration of a seasonal influenza vaccine during the 6 months preceding entry into the study.
* Prior administration of an investigational or licensed coronavirus (SARS-CoV, MERS-CoV, SARS-CoV-2) vaccine except for mRNA-1273 vaccine.
* Any contraindication to the study intervention(s).

Prior/concurrent clinical study experience

• Planning to or concurrently participating in another clinical study (including current / planned simultaneous participation in another interventional study to prevent or treat COVID-19), at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational vaccine / product (drug or medical device).

Other exclusions

* Pregnant or lactating female.
* Female planning to become pregnant or planning to discontinue contraceptive precautions within 2 months following last study vaccination.
* Indications of drug abuse or excess alcohol use as deemed by investigator to potentially confound safety assessments or render participant unable or unlikely to adhere to protocol requirements.

Primary outcomes:
measure: Anti-glycoprotein E (gE) Antibody Concentrations Expressed as Geometric Mean Concentrations (GMCs) in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios
timeFrame: At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)
measure: Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios
timeFrame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups)
measure: Anti-hemagglutinin Inhibition (HI) Antibody Titers Expressed as Geometric Mean Titers (GMTs) Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Ratios
timeFrame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)
measure: Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Ratios
timeFrame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups)
Secondary outcomes:
measure: Percentage of Participants Seroconverted for Anti-HI Antibodies Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Differences
timeFrame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)
measure: Percentage of Participants Seropositive for Anti-gE Antibodies in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group) and at 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)
measure: Anti-gE Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group) and at 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)
measure: Percentage of Participants With a Vaccine Response for Anti-gE in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)
measure: Mean Geometric Increase (MGI) for Anti-gE in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group) compared to pre-vaccination (Week 2 for HZ/suSeq group and Day 1 for HZ/suCoAd group)
measure: Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At pre-vaccination (Day 1) and at 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups)
measure: Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups
timeFrame: At pre-vaccination (Day 1) and at 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups)
measure: Mean Geometric Increase (MGI) for Anti-S Protein in HZ/suSeq and HZ/suCoAd Groups
timeFrame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups) compared to pre-vaccination (Day 1)
measure: Mean Geometric Increase (MGI) for Anti-S Protein in FluD-QIVSeq and FluD-QIVCoAd Groups
timeFrame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups) compared to pre-vaccination (Day 1)
measure: Anti-HI Antibody Titers Expressed as GMTs Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups
timeFrame: At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)
measure: Percentage of Participants Seroprotected for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, Overall and by Age Category
timeFrame: At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)
measure: Percentage of Participants Seropositive for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups
timeFrame: At pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group) and at 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)
measure: Mean Geometric Increase (MGI) for Anti-HI Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups
timeFrame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) compared to pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants Seroconverted for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups, Overall and by Age Category
timeFrame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group) compared to pre-vaccination (Week 2 for FluD-QIVSeq group and Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Local Adverse Events (AEs)
timeFrame: Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Local Adverse Events (AEs)
timeFrame: Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Systemic Adverse Events (AEs)
timeFrame: Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Systemic Adverse Events (AEs)
timeFrame: Within 7 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 14 days after each vaccine dose and across doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 14 days after each vaccine dose and across doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 30 days after each vaccine dose and across vaccine doses (vaccines administered at Day 1, Week 2 and Week 10 for HZ/suSeq group and at Day 1 and Week 8 for HZ/suCoAd group)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs)
timeFrame: Within 30 days after each vaccine dose and across vaccine doses (vaccines administered at Day 1 and Week 2 for FluD-QIVSeq group and at Day 1 for FluD-QIVCoAd group)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs)
timeFrame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs)
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Serious Adverse Events (SAEs)
timeFrame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Serious Adverse Events (SAEs)
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Potential Immune Mediated Diseases (pIMDs)
timeFrame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Potential Immune Mediated Diseases (pIMDs)
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Adverse Events of Special Interest (AESIs)
timeFrame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Adverse Events of Special Interest (AESIs)
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Adverse Events of Special Interest (AESIs)
timeFrame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Adverse Events of Special Interest (AESIs)
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Clinically Suspected HZ Episodes
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Meeting Case Definitions of COVID-19
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
measure: Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Meeting Case Definitions of COVID-19
timeFrame: From first vaccine dose (Day 1) up to study end (24 weeks post-last vaccine dose)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: GSK Investigational Site
state: Arizona
city: Oxnard
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Atlantis
country: United States
facility: GSK Investigational Site
state: Florida
city: Fort Myers
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Lake Worth
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Ocala
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Sarasota
country: United States
facility: GSK Investigational Site
state: Florida
city: Atlanta
country: United States
facility: GSK Investigational Site
state: Georgia
city: Columbus
country: United States
facility: GSK Investigational Site
state: Georgia
city: Meridian
country: United States
facility: GSK Investigational Site
state: Idaho
city: El Dorado
country: United States
facility: GSK Investigational Site
state: Kansas
city: Newton
country: United States
facility: GSK Investigational Site
state: Kansas
city: Topeka
country: United States
facility: GSK Investigational Site
state: Kansas
city: Wichita
country: United States
facility: GSK Investigational Site
state: Kansas
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Biloxi
country: United States
facility: GSK Investigational Site
state: Mississippi
city: Fremont
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Omaha
country: United States
facility: GSK Investigational Site
state: Nebraska
city: Berlin
country: United States
facility: GSK Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Columbus
country: United States
facility: GSK Investigational Site
state: Ohio
city: Norman
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Yukon
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Grants Pass
country: United States
facility: GSK Investigational Site
state: Oregon
city: Anderson
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Beaumont
country: United States
facility: GSK Investigational Site
state: Texas
city: Cedar Park
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Tomball
country: United States
facility: GSK Investigational Site
state: Texas
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: West Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Norfolk
country: United States
facility: GSK Investigational Site
state: Virginia
city: Cheney
country: United States
facility: GSK Investigational Site
state: Washington
city: Tacoma
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: