Study of mRNA Vaccine Formulation Against COVID-19 in Healthy Adults 18 Years of Age and Older
- Conditions
- COVID-19
- Interventions
- Biological: SARS-CoV-2 mRNA vaccine formulation 2Biological: SARS-CoV-2 mRNA vaccine formulation 1Biological: Placebo (0.9% normal saline)Biological: SARS-CoV-2 mRNA vaccine formulation 3
- Registration Number
- NCT04798027
- Lead Sponsor
- Sanofi Pasteur, a Sanofi Company
- Brief Summary
The primary objectives of the study are:
* To describe the safety profile of all participants in each age group and each study intervention group up to 12 months post-last dose.
* To describe the neutralizing antibody profile at Day 1, Day 22, and Day 36 of each study intervention group.
The secondary objectives of the study are:
* To describe binding antibody profile from Day 1 to Day 387 of each study intervention group.
* To describe the neutralizing antibody profile from Day 91 to Day 387 of each study intervention group.
* To describe the occurrence of virologically-confirmed coronavirus disease-2019 (COVID-19)-like illness and serologically-confirmed SARS-CoV-2 infection.
* To evaluate the correlation/association between antibody responses to SARS-CoV-2 messenger RNA (mRNA) vaccine and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection.
- Detailed Description
The duration of each participant's participation in the study was approximately 365 days post-last injection: approximately 386 days duration for participants receiving 2 injections and approximately 365 days duration total for participants receiving a single injection.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 182
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Sentinel Cohort: SARS-CoV-2 Vaccine Low dose SARS-CoV-2 mRNA vaccine formulation 2 Participants received two IM injections of SARS-CoV-2 Vaccine low dose on Day 1 and at Day 22, respectively. FEC Cohort 1: SARS-CoV-2 Vaccine Ultra Low dose SARS-CoV-2 mRNA vaccine formulation 1 Participants received a single IM injection of SARS-CoV-2 Vaccine ultra-low dose on Day 1. Sentinel Cohort: SARS-CoV-2 Vaccine Ultra Low dose SARS-CoV-2 mRNA vaccine formulation 1 Participants received two intramuscular (IM) injections of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Vaccine ultra-low dose on Day 1 and at Day 22, respectively. FEC Cohort 1: SARS-CoV-2 Vaccine Low dose SARS-CoV-2 mRNA vaccine formulation 2 Participants received a single IM injection of SARS-CoV-2 Vaccine low dose on Day 1. FEC Cohort 1: Placebo Placebo (0.9% normal saline) Participants received a single IM injection of placebo matched to SARS-CoV-2 Vaccine on Day 1. Sentinel Cohort: SARS-CoV-2 Vaccine Medium dose SARS-CoV-2 mRNA vaccine formulation 3 Participants received two IM injections of SARS-CoV-2 Vaccine medium dose on Day 1 and at Day 22, respectively. FEC Cohort 2: SARS-CoV-2 Vaccine Ultra Low dose SARS-CoV-2 mRNA vaccine formulation 1 Participants received two IM injections of SARS-CoV-2 Vaccine ultra-low dose on Day 1 and at Day 22, respectively. FEC Cohort 2: SARS-CoV-2 Vaccine Low dose SARS-CoV-2 mRNA vaccine formulation 2 Participants received two IM injections of SARS-CoV-2 Vaccine low dose on Day 1 and at Day 22, respectively. FEC Cohort 2: Placebo Placebo (0.9% normal saline) Participants received two IM injections of placebo matched to SARS-CoV-2 Vaccine on Day 1 and at Day 22, respectively.
- Primary Outcome Measures
Name Time Method Number of Participants With Solicited Injection Site Reactions Within 7 days after any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22]) Solicited reaction (SR): expected adverse reaction (sign or symptom) observed \& reported under conditions (nature \& onset) prelisted (i.e., solicited) in CRF and considered as related to product administered. Solicited injection site reactions included pain, erythema, \& swelling. Reported AEs for each arm were presented as pre-specified in study protocol. In the data table, '0' in number analyzed field denotes that no participants were available for assessment for specified Group as no one in that group received vaccination 2.
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine at Day 36 Day 36 (post-vaccination) GMTs of SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Number of Participants With Unsolicited Adverse Events Within 21 days after any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22]) An AE was any untoward medical occurrence in a clinical investigation participant administered a medicinal product and which did not have any casual relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF in terms of diagnosis and/or onset window post-vaccination. Reported AEs for each arm were presented as pre-specified in the study protocol. In the data table, '0' in number analyzed field denotes that no participants were available for assessment for specified Group as no one in that group received vaccination 2.
Number of Participants Reporting Serious Adverse Events (SAEs), Adverse Event of Special Interest (AESIs) and Medically Attended Adverse Events (MAAEs) From Day 1 until 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 groups and up to Day 387 for Cohort 2 groups) SAEs: any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. AESIs: event for which ongoing monitoring \& rapid communication by investigator to the sponsor was done. MAAE was a new onset or worsening of a condition that prompted participant or participant's parent/legally acceptable representative to seek unplanned medical advice at physician's office or emergency department. Reported AEs for each arm were presented as pre-specified in study protocol.
Geometric Mean Fold-rise (GMFR) of Serum Neutralization Antibody Titers at Day 22 Day 1 (pre-vaccination) and Day 22 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Fold-rise was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (Day 22) and pre-vaccination (on Day 1) i.e., Day 22/Day 1.
Number of Participants Reporting Immediate Unsolicited Adverse Events (AEs) Within 30 minutes post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22]) AE: any untoward medical occurrence in clinical investigation participant administered medicinal product \& which did not have any causal relationship with the treatment. Unsolicited AE: observed AE that did not fulfill conditions prelisted in case report form (CRF) in terms of diagnosis \&/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, \& any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in CRF. Reported AEs were presented as pre-specified in protocol. In the data table, '0' in number analyzed field denotes that no participants were available for assessment for specified Group as no one in that group received vaccination 2.
Number of Participants With Solicited Systemic Reactions Within 7 days after any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22]) SR was an expected adverse reaction (sign or symptom) observed \& reported under conditions (nature \& onset) prelisted (i.e., solicited) in CRF \& considered as related to product administered. Solicited systemic reactions included fever, headache, malaise, myalgia, arthralgia \& chills. Reported AEs for each arm were presented as pre-specified in study protocol. In the data table, '0' in number analyzed field denotes that no participants were available for assessment for specified Group as no one in that group received vaccination 2.
Number of Participants With Laboratory Test Results Based on US Food and Drug Administration (FDA) Toxicity Grading Guidance From Day 1 up to up to 8 days post last vaccination (i.e., up to Day 9 for Cohort 1 groups; up to Day 30 for Cohort 2 groups) Laboratory tests: hemoglobin (male \& female), above \& below normal white blood cell, lymphocytes, neutrophils \& eosinophils, platelet count, creatinine \& blood urea nitrogen, hyponatremia \& hypernatremia, hyperkalemia \& hypokalemia, hyperglycemia (non-fasting), hypoproteinemia, alkaline phosphate, alanine aminotransferase, aspartate aminotransferase, bilirubin (with any increase in liver function test \[LFT\], bilirubin (normal LFT), prothrombin \& partial thromboplastin time (seconds), Urine: protein, glucose \& blood. US FDA "Toxicity Grading Scale for Healthy Adults \& Adolescent Volunteers" was used for grading; Grade 1=mild, Grade 2=moderate \& Grade 3=severe. In the data table, 'number analyzed'=participants with available data for each specified category \& '0'=none of participants were available for assessment for specified Group.
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine at Day 1 Day 1 (pre-vaccination) GMTs of SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Titers were expressed in terms of 1/dilution. Data for this OM was planned to be collected and analyzed for combined population (FEC+ Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine at Day 22 Day 22 (post-vaccination) GMTs of SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Geometric Mean Fold-rise of Serum Neutralization Antibody Titers at Day 36 Day 1 (pre-vaccination) and Day 36 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Fold-rise was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (Day 36) and pre-vaccination (on Day 1) i.e., Day 36/Day 1.
Percentage of Participants With >=2-fold and >=4-fold Rise in Serum Neutralization Antibody Titers at Day 22 Day 1 (pre-vaccination) and Day 22 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (on Day 22) and pre-vaccination (on Day 1) i.e., Day 22/Day 1.
Percentage of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titer at Day 36 Day 1 (pre-vaccination) and Day 36 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of neutralizing antibodies post-vaccination (on Day 36) and pre-vaccination (on Day 1) i.e., Day 36/Day 1.
Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 22 Day 22 (post-vaccination) Seroconversion was defined as participants with a Baseline (Day 1) titer values below lower limit of quantification (LLOQ) with a detectable neutralization antibody titer above assay LLOQ post injection (at Day 22). LLOQ of the neutralization assay was a titer of 10.
Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 36 Day 36 (post-vaccination) Seroconversion was defined as participants with a Baseline (Day 1) titer values below LLOQ with a detectable neutralization antibody titer above assay LLOQ post injection (at Day 36). LLOQ of the neutralization assay was a titer of 10.
- Secondary Outcome Measures
Name Time Method Geometric Mean Titers of Neutralizing Antibody Titer Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 91, 112, 181, and 202 Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination) GMTs of SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Titers were expressed in terms of 1/dilution. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 91, 112, 181, and 202 Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2) Binding antibody titers were evaluated by ELISA. Fold-rise was calculated as the ratio of geometric mean concentrations of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Day 22/Day 1, Day 36/Day 1, Day 91/Day 1, Day 112/Day 1, Day 181/Day 1, and Day 202/Day 1. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 91, 112, 181, and 202 Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2) GMC of Anti-S binding antibodies were assessed using enzyme-linked immunosorbent assay (ELISA) and were measured in ELISA unit/mL (ELU/mL). Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Percentage of Participants With >=2- and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 91, 112, 181, and 202 Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 91 (only for Cohort 1), Day 112 (only for Cohort 2), Day 181 (only for Cohort 1), and Day 202 (only for Cohort 2) Binding antibody titers were evaluated by ELISA. Fold-rise (2-fold and 4-fold) was calculated as the ratio of geometric mean concentrations of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Day 22/Day 1, Day 36/Day 1, Day 91/Day 1, Day 112/Day 1, Day 181/Day 1, and Day 202/Day 1. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 91, 112, 181, and 202 Day 1 (pre-vaccination), Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Fold-rise was calculated as the ratio of titer values of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., for Cohort 1: Day 91/Day 1, Day 181/Day 1; Cohort 2: Day 112/Day 1, and Day 202/Day 1. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Number of Participants With Serologically-confirmed SARS-CoV-2 Infection Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination) Serologically-confirmed SARS-CoV-2 infection as defined by SARS-CoV-2 Nucleoprotein specific antibody detection immunoassay was reported in this outcome measure.
Percentage of Participants With 2-Fold and 4-Fold Rise in Serum Neutralization Antibody Titer at Day 91, 112, 181, and 202 Day 1 (pre-vaccination), Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination) SARS-CoV-2 neutralizing antibodies (D614G variant) was measured using a neutralization assay. Fold-rise (2-fold and 4-fold) was calculated as the ratio of geometric mean concentrations of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Day 91/Day 1, Day 112/Day 1, Day 181/Day 1, and Day 202/Day 1. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens Cohort 1: Day 91, Day 181 and Cohort 2: Day 112, and Day 202 (post-vaccination) Seroconversion was defined as participants with a Baseline (Day 1) titer values below lower limit of quantification (LLOQ) with a detectable neutralization antibody titer above assay LLOQ post injection. LLOQ of the neutralization assay was a titer of 10. Data for this OM was planned to be collected and analyzed for combined population (FEC + Sentinel Cohort) in which same dose-level groups in Sentinel Cohort and FEC were pooled for analysis.
Number of Participants With Virologically-confirmed Coronavirus Disease (COVID-19)-Like Illness Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination) Virologically-confirmed COVID-19-like illness was defined by specified clinical symptoms and signs and confirmed by positive result for SARS-CoV-2 by nucleic acid amplification test (NAAT) on a respiratory sample in association with a COVID-19-like illness.
Correlates of Risk/Protection Based on Antibody Responses to SARS-CoV-2 Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination) Correlate of risk / protection based on antibody responses to SARS-CoV-2 was evaluated using virus neutralization or ELISA, considering virologically-confirmed COVID-19-like illness and/or serologically-confirmed SARS-CoV-2 infection.
Trial Locations
- Locations (21)
Investigational Site Number :8400003
🇺🇸Rolling Hills Estates, California, United States
Investigational Site Number :8400002
🇺🇸Hollywood, Florida, United States
Investigational Site Number :8400017
🇺🇸Iowa City, Iowa, United States
Investigational Site Number :8400001
🇺🇸Rochester, New York, United States
Investigational Site Number :8400004
🇺🇸North Charleston, South Carolina, United States
Investigational Site Number :8400015
🇺🇸Knoxville, Tennessee, United States
Investigational Site Number :0360003
🇦🇺Morayfield, Queensland, Australia
Investigational Site Number :0360005
🇦🇺South Brisbane, Queensland, Australia
Investigational Site Number :0360001
🇦🇺Melbourne, Victoria, Australia
Investigational Site Number :0760004
🇧🇷Campo Grande, Mato Grosso Do Sul, Brazil
Investigational Site Number :0360002
🇦🇺Nedlands, Western Australia, Australia
Investigational Site Number :3400002
🇭🇳Barrio Del Centro, Honduras
Investigational Site Number :3400001
🇭🇳San Pedro Sula, Honduras
Investigational Site Number :0760001
🇧🇷Salvador, Bahia, Brazil
Investigational Site Number :0760003
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Investigational Site Number :8400006
🇺🇸Miami, Florida, United States
Investigational Site Number :8400007
🇺🇸Kansas City, Missouri, United States
Investigational Site Number :8400008
🇺🇸Omaha, Nebraska, United States
Investigational Site Number :8400010
🇺🇸Philadelphia, Pennsylvania, United States
Investigational Site Number :8400009
🇺🇸Houston, Texas, United States
Investigational Site Number :8400005
🇺🇸Salt Lake City, Utah, United States