Clinical trial NCT04956575: A Study of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults
Official title: A Phase 1/2, Randomized, Stratified, Observer-Blind, Dose-Ranging Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of mRNA-1010 Seasonal Influenza Vaccine in Healthy Adults 18 Years and Older
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Seasonal Influenza
Keywords: Influenza vaccine
mRNA-1010
Moderna
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-09
Enrollment: 885
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 study comprises 3 parts: Phase 1/2, Phase 2 Northern Hemisphere (NH), and Phase 2 extension. The primary objective of this study is to evaluate the safety, reactogenicity, and humoral immunogenicity of mRNA-1010 vaccine.


Eligibility criteria: Key Inclusion Criteria:

Phase 1/2:

* Participant has a body mass index (BMI) of 18 kilograms (kg)/square meter (m\^2) to 35 kg/m\^2 (inclusive) at the Screening Visit.
* Participant is in good health, in the opinion of the Investigator, based on review of medical history and physical examination performed at screening.
* For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding.

Phase 2 NH and Phase 2 Extension:

* Participant is medically stable, in the opinion of the Investigator, based on review of medical history and physical examination performed at screening.
* For female participants of childbearing potential: negative pregnancy test, adequate contraception or has abstained from all activities that could result in pregnancy for at least 28 days prior to Day 1, agreement to continue adequate contraception through 3 months following vaccine administration, and not currently breastfeeding.

Key Exclusion Criteria:

Phase 1/2:

* Participant has had significant exposure to someone with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19, or influenza-like illness (ILI) in the past 14 days prior to the Screening Visit, as defined by the United States Centers for Disease Control and Prevention (CDC) as close contact with someone who has COVID-19.
* Participant has a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) or antigen test in the past 10 days prior to the Screening Visit.
* Participant is acutely ill or febrile (body temperature ≥ 38.0 degrees Celsius \[°C\]/100.4 degrees Fahrenheit \[°F\]) 72 hours prior to or at the Screening Visit or Day 1.
* Participant has a pre-existing medical condition that is not stable, at the discretion of the Investigator.
* Participant has a medical, psychiatric, or occupational condition that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment.
* Participant has received systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 6 months prior to Screening Visit (for corticosteroids ≥10 milligrams \[mg\]/day of prednisone equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study.
* Participant has received or plans to receive any licensed vaccine ≤28 days prior to the investigational product (IP) injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed.
* Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine after 01 January 2021.

Phase 2 NH:

* Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the CDC (CDC 2021a) in the past 14 days prior to the Screening Visit, unless the participant has been fully vaccinated for COVID-19.
* Participant is acutely ill or febrile (body temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the 28-day screening window and will retain their initially assigned participant number.
* Participant has a medical, psychiatric, occupational condition, or history of substance abuse that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment.
* Participant has a current or previous diagnosis of immunocompromising/immunosuppressive condition, immune mediated disease requiring immune-modifying therapy, asplenia, recurrent severe infections (human immunodeficiency virus \[HIV\] positive participants on antiretroviral therapy with cluster of differentiation \[CD\] 4 count ≥ 350 cells/mm3 and HIV RNA ≤ 500 copies/mL within the past 12 months are permitted).
* Participant has received systemic immunosuppressants or immune-modifying drugs for \> 14 days in total within 6 months prior to Screening Visit (for corticosteroids ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study.
* Participant has a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or any of the components contained in the mRNA 1010 or the comparator vaccine, which is an egg-based influenza vaccine.
* Participant has received or plans to receive any licensed vaccine ≤ 28 days prior to the IP injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed.
* Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 6 months prior to the Screening Visit.
* Participant has tested positive for influenza by CDC-recommended testing methods within 6 months prior to the Screening Visit.
* Participant has participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study.

Phase 2 Extension:

* Participant has had close contact to someone with SARS-CoV-2 infection or COVID-19 as defined by the CDC in the past 10 days prior to the Screening Visit.
* Participant is acutely ill or febrile (body temperature ≥ 38.0°C/100.4°F) 72 hours prior to or at the Screening Visit or Day 1. Participants meeting this criterion may be rescheduled within the 28-day screening window and will retain their initially assigned participant number.
* Participant has a medical, psychiatric, occupational condition, or history of substance abuse that may pose additional risk as a result of participation or that could interfere with safety assessments or interpretation of results according to the Investigator's judgment.
* Participant has a current or previous diagnosis of immunocompromising/immunosuppressive condition, immune-mediated disease requiring immune-modifying therapy, asplenia, recurrent severe infections (HIV-positive participants on antiretroviral therapy with CD 4 count ≥ 350 cells/mm\^3 and HIV-RNA ≤ 500 copies/mL within the past 365 days are permitted).
* Participant has received systemic immunosuppressants or immune-modifying drugs for \>14 days in total within 180 days prior to Screening Visit (for corticosteroids ≥ 10 mg/day of prednisone or equivalent) or is anticipating the need for systemic immunosuppressive treatment at any time during participation in the study.
* Participant has a history of anaphylaxis, urticaria, or other significant AR requiring medical intervention after receipt of a vaccine or any of the components contained in the mRNA-1010 or the comparator vaccine, which is an egg-based influenza vaccine.
* Participant has received or plans to receive any licensed vaccine ≤ 28 days prior to the IP injection (Day 1) or plans to receive a licensed vaccine within 28 days after the IP injection, with the exception of vaccines authorized or approved for the prevention of COVID-19 (regardless of type of vaccine) that become available to participants during the study. Efforts should be made to space study vaccination and COVID-19 vaccination by at least 7 and preferably 14 days, but COVID-19 vaccination should not be delayed.
* Participant has received a seasonal influenza vaccine or any other investigational influenza vaccine within 180 days prior to the randomization visit.
* Participant had tested positive for influenza by CDC-recommended testing methods within 180 days prior to the Screening Visit.
* Participant has participated in an interventional clinical study within 28 days prior to the Screening Visit based on the medical history interview or plans to do so while participating in this study.

Other inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Solicited Local and Systemic ARs
timeFrame: 7 days after vaccination
measure: Number of Participants With Unsolicited AEs
timeFrame: Up to 28 days after vaccination
measure: Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs)
timeFrame: Up to 6 months (end of study)
measure: Phase 1/2: Geometric Mean Titer (GMT) of Anti-Hemagglutinin (HA) Antibodies at Day 29, as Measured by Hemagglutination Inhibition (HAI) Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 29
measure: Phase 2 NH: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 29
measure: Phase 2 Extension: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 29
measure: Phase 1/2: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
timeFrame: Day 29
measure: Phase 1/2: Geometric Mean Fold-Rise (GMFR) of Anti-HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 1 (Baseline), Day 29
measure: Phase 2 NH: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
timeFrame: Day 29
measure: Phase 2 Extension: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
timeFrame: Day 29
Secondary outcomes:
measure: Phase 1/2: GMT of Anti-HA Antibodies at Days 1, 8 and 181, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 1 (Baseline), Day 8 and Day 181
measure: Phase 1/2: GMFR of Anti-HA Antibodies at Days 8 and 181, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 1 (Baseline), Day 8 and Day 181
measure: Phase 2 NH and Phase 2 Extension: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
timeFrame: Day 29
measure: Phase 2 NH and Phase 2 Extension: GMFR of Anti-HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
timeFrame: Day 29
measure: Phase 2 NH and Phase 2 Extension: Percentage of Participants With HAI Titer ≥1:40 at Day 29
timeFrame: Day 29
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Cognitive Clinical Trials - Phoenix
state: Arizona
city: Tempe
country: United States
facility: Alliance for Multispecialty Research, LLC - Phoenix
state: Arizona
city: Colton
country: United States
facility: Benchmark Research - Colton, CA
state: California
city: Hollywood
country: United States
facility: Research Centers of America - ERGG - PPDS
state: Florida
city: Savannah
country: United States
facility: Meridian Clinical Research (Savannah Georgia) - Platinum - PPDS
state: Georgia
city: Sioux City
country: United States
facility: Meridian Clinical Research
state: Iowa
city: Lenexa
country: United States
facility: Johnson County Clin-Trials
state: Kansas
city: Baton Rouge
country: United States
facility: Meridian Clinical Research - Baton Rouge
state: Louisiana
city: Rockville
country: United States
facility: Meridian Clinical Research
state: Maryland
city: Grand Island
country: United States
facility: Meridian Clinical Research (Grand Island)
state: Nebraska
city: Lincoln
country: United States
facility: Meridian Clinical Research, LLC (Lincoln Nebraska)
state: Nebraska
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Endwell
country: United States
facility: Meridian Clinical Research (Endwell-New York) - Platinum - PPDS
state: New York
city: Morehead City
country: United States
facility: Lucas Research
state: North Carolina
city: Wilmington
country: United States
facility: Trial Management Associates LLC - ERN - PPDS
state: North Carolina
city: Cincinnati
country: United States
facility: Meridian Clinical Research - Cincinnati - Platinum - PPDS
state: Ohio
city: Cincinnati
country: United States
facility: Meridian Clinical Research - Cincinnati - Platinum - PPDS
state: Ohio
city: Greenville
country: United States
facility: Keystone VitaLink Research - Greenville - PPDS
state: South Carolina
city: Brownsville
country: United States
facility: PanAmerican Clinical Research LLC
state: Texas
city: Plano
country: United States
facility: Research Your Health - ERN - PPDS
state: Texas
city: South Ogden
country: United States
facility: South Ogden Family Medicine/Ogden Clinic - CCT
state: Utah
Study officials:
References:
citation: Lee IT, Nachbagauer R, Ensz D, Schwartz H, Carmona L, Schaefers K, Avanesov A, Stadlbauer D, Henry C, Chen R, Huang W, Schrempp DR, Ananworanich J, Paris R. Safety and immunogenicity of a phase 1/2 randomized clinical trial of a quadrivalent, mRNA-based seasonal influenza vaccine (mRNA-1010) in healthy adults: interim analysis. Nat Commun. 2023 Jun 19;14(1):3631. doi: 10.1038/s41467-023-39376-7.