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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
885
Sterile liquid for injection
0.9% sodium chloride solution for injection
0.5 milliliter (mL) intramuscular (IM) injection
Cognitive Clinical Trials - Phoenix
Phoenix, Arizona, United States
Number of Participants With Solicited Local and Systemic ARs
Solicited ARs (local and systemic) were collected in the electronic diary (eDiary). Local ARs included: pain at injection site, erythema (redness) at injection site, swelling/induration (hardness) at injection site, and localized axillary swelling or tenderness ipsilateral to the injection arm. Systemic ARs included: headache, fatigue, myalgia (muscle aches all over the body), arthralgia (aching in several joints), nausea/vomiting, rash, body temperature (potentially fever), and chills. Solicited ARs (local and systemic) considered causally related to injection were graded 0-4; lower score indicates lower severity and a higher score indicates greater severity. Note, not all solicited ARs were considered adverse events (AEs). The Investigator reviewed whether the solicited AR was also to be recorded as an AE. Summary of serious AEs (SAEs) and nonserious AEs ("Other"), regardless of causality, is in Reported "Adverse Events" section and presented by Phase/dose group.
Time frame: 7 days after vaccination
Number of Participants With Unsolicited AEs
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. A treatment-emergent AE (TEAE) was defined as any event not present before exposure to vaccine or any event already present that worsens in intensity or frequency after exposure. Any abnormal laboratory test result (hematology, clinical chemistry, or prothrombin time \[PT\]/partial thromboplastin time \[PTT\]) or other safety assessment (for example, electrocardiogram, radiological scan, vital sign measurement), including one that worsens from baseline and is considered clinically significant in the medical and scientific judgment of the Investigator. A summary of SAEs and all nonserious AEs ("Other") reported up to the end of the study, regardless of causality, is located in the Reported "Adverse Events" section and presented by each Phase and dose group separately.
Time frame: Up to 28 days after vaccination
Number of Participants With SAEs, AEs of Special Interest (AESIs), Medically Attended AEs (MAAEs)
An SAE was defined as any AE that resulted in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in disability/permanent damage, was a congenital anomaly/birth defect, or was an important medical event. AESIs included thrombocytopenia, new onset of or worsening of the protocol specified neurologic diseases, anaphylaxis, and myocarditis/pericarditis. An MAAE is an AE that leads to an unscheduled visit to an healthcare practitioner. This would include visits to a study site for unscheduled assessments (for example, abnormal laboratory follow-up, and/or COVID-19 and visits to healthcare practitioners external to the study site (for example, urgent care, primary care physician). A summary of SAEs and all nonserious AEs ("Other"), regardless of causality, is located in the Reported "Adverse Events" section and presented by each Phase and dose group separately.
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Alliance for Multispecialty Research, LLC - Phoenix
Tempe, Arizona, United States
Benchmark Research - Colton, CA
Colton, California, United States
Research Centers of America - ERGG - PPDS
Hollywood, Florida, United States
Meridian Clinical Research (Savannah Georgia) - Platinum - PPDS
Savannah, Georgia, United States
Meridian Clinical Research
Sioux City, Iowa, United States
Johnson County Clin-Trials
Lenexa, Kansas, United States
Meridian Clinical Research - Baton Rouge
Baton Rouge, Louisiana, United States
Meridian Clinical Research
Rockville, Maryland, United States
Meridian Clinical Research (Grand Island)
Grand Island, Nebraska, United States
...and 11 more locations
Time frame: Up to 6 months (end of study)
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
Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% confidence interval (CI) was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29
Phase 2 NH: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29
Phase 2 Extension: GMT of HA Antibodies at Day 29, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B Strains
Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 29
Phase 1/2: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if lower limit of quantification (LLOQ) was 1:10, a post-baseline titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was \>1:10, a post-baseline titer ≥4 x LLOQ if baseline was \<LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies.
Time frame: Day 29
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
The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation.
Time frame: Day 1 (Baseline), Day 29
Phase 2 NH: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if LLOQ was 1:10, a post-baseline titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was \>1:10, a post-baseline titer ≥4 x LLOQ if baseline was \<LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. 95% CI was calculated using the Clopper-Pearson method
Time frame: Day 29
Phase 2 Extension: Percentage of Participants With Seroconversion, as Measured by HAI Assay for Vaccine-Matched Seasonal Influenza A and B
Humoral immunogenicity relative to that of the active comparator (afluria quadrivalent) was assessed against vaccine-matched Influenza A and B strains at Day 29. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if LLOQ was 1:10, a post-baseline titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was \>1:10, a post-baseline titer ≥4 x LLOQ if baseline was \<LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies. 95% CI was calculated using the Clopper-Pearson method
Time frame: Day 29
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
Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. GMT 95% CI was calculated based on the t-distribution of the log-transformed values then back transformed to the original scale for presentation.
Time frame: Day 1 (Baseline), Day 8 and Day 181
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
The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMT, then back transformed to the original scale for presentation.
Time frame: Day 1 (Baseline), Day 8 and Day 181
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
Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. Seroconversion at a participant level was defined as (a) if lower limit of quantification (LLOQ) was 1:10, a post-baseline titer ≥1:40 if baseline was \<1:10 or a 4-fold or greater rise from baseline if baseline was ≥1:10 in anti-HA antibodies; or (b) if LLOQ was \>1:10, a post-baseline titer ≥4 x LLOQ if baseline was \<LLOQ, or 4-fold or greater increase from baseline if baseline was ≥LLOQ in anti-HA antibodies.
Time frame: Day 29
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
The GMFR measures the changes in immunogenicity titers or levels from Baseline within participants. Seasonal influenza A included H1N1 and H3N2 and seasonal influenza B strains included Victoria-lineage and Yamagata-lineage. 95% CI was calculated based on the difference in the log-transformed values for GMFR, then back transformed to the original scale for presentation.
Time frame: Day 29
Phase 2 NH and Phase 2 Extension: Percentage of Participants With HAI Titer ≥1:40 at Day 29
Time frame: Day 29