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 | Crick

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

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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.

Outcomes

Primary Outcomes

Anti-glycoprotein E (gE) Antibody Concentrations Expressed as Geometric Mean Concentrations (GMCs) in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios

Anti-gE antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as GMCs in milli-international units per milliliter (mIU/mL).

Time frame: At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)

Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups, and Between-group Ratios

Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in arbitrary units per milliliter (AU/mL).

Time frame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both HZ/suSeq and HZ/suCoAd groups)

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

Antibody titers against the 4 influenza strains (A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage) included in the FLU D-QIV vaccine were determined by hemagglutination inhibition and expressed as GMTs.

Time frame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)

Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups, and Between-group Ratios

Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL.

Time frame: At 1 month post-mRNA-1273 booster dose administration (Week 4 for both FluD-QIVSeq and FluD-QIVCoAd groups)

Secondary Outcomes

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

A participant seroconverted for anti-HI antibodies against the 4 influenza strains is defined as a participant having either a pre-vaccination HI titer below (\<) 1:10 and a post-vaccination HI titer greater than or equal to (≥) 1:40, or a pre-vaccination HI titer ≥ 1:10 and at least a 4 fold greater post-vaccination HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage.

Time frame: At 1 month post-Flu D-QIV vaccine dose administration (Week 6 for FluD-QIVSeq group and Week 4 for FluD-QIVCoAd group)

Percentage of Participants Seropositive for Anti-gE Antibodies in HZ/suSeq and HZ/suCoAd Groups

A participant seropositive for anti-gE antibodies is defined as a participant whose anti-gE antibody concentration was greater than or equal to the assay cut-off value (97 mIU/mL).

Time frame: 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)

Anti-gE Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups

Anti-gE antibody concentrations were determined by ELISA and expressed as GMCs in mIU/mL.

Percentage of Participants With a Vaccine Response for Anti-gE in HZ/suSeq and HZ/suCoAd Groups

A participant with vaccine response for anti-gE is defined as a participant with: * At least a 4-fold greater post-dose anti-gE antibodies concentration as compared to the pre-vaccination anti-gE antibodies concentration, for participants who were seropositive at pre-vaccination, or, * At least a 4-fold greater post-dose anti-gE antibodies concentration as compared to the anti-gE antibodies cut-off value for seropositivity, for participants who were seronegative at pre-vaccination.

Time frame: At 1 month post-dose 2 of HZ/su vaccine administration (Week 14 for HZ/suSeq group and Week 12 for HZ/suCoAd group)

Mean Geometric Increase (MGI) for Anti-gE in HZ/suSeq and HZ/suCoAd Groups

MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-gE antibody concentration to the pre-vaccination anti-gE antibody concentration.

Time frame: 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)

Anti-S Protein Antibody Concentrations Expressed as GMCs in HZ/suSeq and HZ/suCoAd Groups

Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL.

Time frame: 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)

Anti-S Protein Antibody Concentrations Expressed as GMCs in FluD-QIVSeq and FluD-QIVCoAd Groups

Anti-S antibody concentrations were determined by Multiplex Electrochemiluminescence assay and expressed as GMCs in AU/mL.

Time frame: 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)

Mean Geometric Increase (MGI) for Anti-S Protein in HZ/suSeq and HZ/suCoAd Groups

MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-S protein antibody concentration to the pre-vaccination anti-S protein antibody concentration.

Time frame: 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)

Mean Geometric Increase (MGI) for Anti-S Protein in FluD-QIVSeq and FluD-QIVCoAd Groups

MGI is defined as the geometric mean of the within participant ratios of the post-vaccination anti-S protein antibody concentration to the pre-vaccination anti-S protein antibody concentration.

Time frame: 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)

Anti-HI Antibody Titers Expressed as GMTs Against the 4 Influenza Strains in Flu D-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups

Time frame: 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)

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

A participant seroprotected for anti-HI antibodies against the 4 influenza strains included in the FluD-QIV vaccine is defined as a participant with a serum HI titer ≥ 1:40. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. The age categories assessed were 18-64 and ≥ 65 years of age (YOA).

Percentage of Participants Seropositive for Anti-HI Antibodies Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups

A participant seropositive for anti-HI antibodies against the 4 influenza strains included in the FluD-QIV vaccine is defined as a participant with a serum HI titer ≥ 1:10. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage.

Mean Geometric Increase (MGI) for Anti-HI Against the 4 Influenza Strains in FluD-QIV Vaccine in FluD-QIVSeq and FluD-QIVCoAd Groups

MGI is defined as the geometric mean of the within participant ratios of the post-vaccination reciprocal HI titer to the pre-vaccination reciprocal HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage.

Time frame: 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)

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

A participant seroconverted for anti-HI antibodies against the 4 influenza strains is defined as a participant having either a pre-vaccination HI titer \< 1:10 and a post-vaccination HI titer ≥ 1:40, or a pre-vaccination HI titer ≥ 1:10 and at least a 4 fold greater post-vaccination HI titer. The 4 influenza strains assessed were A/H1N1 strain, A/H3N2 strain, B/Victoria lineage and B/Yamagata lineage. The age categories assessed were 18-64 and ≥65 years of age (YOA).

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Local Adverse Events (AEs)

The assessed solicited local AEs included axillary (underarm) swelling or tenderness, pain, pruritus, redness and swelling. Axillary swelling or tenderness was solicited for all participants and not restricted to mRNA-1273 recipients as was originally planned per protocol. Pruritus was solicited for all participants and not restricted to HZ/su recipients as was originally planned per protocol.

Time frame: 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)

Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Local Adverse Events (AEs)

Time frame: 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)

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Solicited Systemic Adverse Events (AEs)

The assessed solicited systemic AEs included abdominal pain, arthralgia, chills, diarrhea, fatigue, fever, gastrointestinal symptoms, headache, myalgia, nausea and vomiting. Fever is defined as temperature ≥ 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F) by any route. The preferred location for measuring temperature was the oral route.

Time frame: 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)

Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Solicited Systemic Adverse Events (AEs)

The assessed solicited systemic AEs included abdominal pain, arthralgia, chills, diarrhea, fatigue, fever, gastrointestinal symptoms, headache, myalgia, nausea and vomiting. Fever is defined as temperature ≥ 38.0°C/100.4°F by any route. The preferred location for measuring temperature was the oral route.

Time frame: 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)

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs)

An unsolicited AE was defined as any AE that was either not included in the list of solicited events using a participant diary, or was included in the list of solicited events, but with an onset more than 7 days following administration of a study intervention.

Time frame: 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)

Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs)

Time frame: 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)

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Unsolicited Adverse Events (AEs)

Time frame: 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)

Percentage of Participants in FluD-QIVSeq and FluD-QIVCoAd Groups Reporting Unsolicited Adverse Events (AEs)

Time frame: 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)

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs)

An SAE was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect in the offspring of a study participant, was considered or defined as an important medical event, or abnormal pregnancy outcomes.

Time frame: From first vaccine dose (Day 1) up to 30 days post-last vaccine dose within each group

Percentage of Participants in HZ/suSeq and HZ/suCoAd Groups Reporting Serious Adverse Events (SAEs)