Back to resultsStudy of Recombinant Protein Vaccine Formulations Against COVID-19 in Healthy Adults 18 Years of Age and Older
Primary Purpose
COVID-19 (Healthy Volunteers)
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CoV2 preS dTM-AF03 (low-dose)
CoV2 preS dTM-AF03 (high-dose)
CoV2 preS dTM-AS03 (low-dose)
CoV2 preS dTM-AS03 (high-dose)
CoV2 preS dTM (high-dose) without adjuvant
Placebo (0.9% normal saline)
Sponsored by
About this trial
This is an interventional prevention trial for COVID-19 (Healthy Volunteers)
Eligibility Criteria
Inclusion Criteria:
- Aged 18 years of age or older on the day of inclusion
- Informed consent form has been signed and dated
- Able to attend all scheduled visits and to comply with all study procedures
Exclusion Criteria:
- Participant is pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination. To be considered of non-childbearing potential, a female must be post-menopausal for at least 1 year or surgically sterile
- Receipt of any vaccine in the 30 days preceding the first study vaccination or planned receipt of any vaccine in the 30 days following the last study vaccination except for influenza vaccination, which may be received at least 2 weeks before and a minimum of 2 weeks after study vaccines
- Prior administration of a coronavirus vaccine (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], SARS-CoV, Middle East Respiratory Syndrome)
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- History of SARS-CoV-2 infection, confirmed either clinically, serologically, or microbiologically
- Chronic illness or condition considered to potentially increase the risk for severe COVID illness or that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
- Receipt of any therapy known to have in-vitro antiviral activity against SARS-CoV-2 within 72 hours prior to the first blood draw
- Health care workers providing direct patient care for COVID-19 patients
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Sites / Locations
- Investigational Site Number 8400004
- Investigational Site Number 8400012
- Investigational Site Number 8400011
- Investigational Site Number 8400019
- Investigational Site Number 8400016
- Investigational Site Number 8400002
- Investigational Site Number 8400001
- Investigational Site Number 8400007
- Investigational Site Number 8400008
- Investigational Site Number 8400003
- Investigational Site Number 8400014
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Cohort 1: Group 1: SARS-CoV-2 vaccine LD + AF03
Cohort 1: Group 2: SARS-CoV-2 vaccine LD + AS03
Cohort 1: Group 3: SARS-CoV-2 vaccine HD + AF03
Cohort 1: Group 4: SARS-CoV-2 vaccine HD + AS03
Cohort 1: Group 5: Placebo
Cohort 2: Group 6: SARS-CoV-2 vaccine LD + AF03
Cohort 2: Group 7: SARS-CoV-2 vaccine LD + AS03
Cohort 2: Group 8: SARS-CoV-2 vaccine HD + AF03
Cohort 2: Group 9: SARS-CoV-2 vaccine HD + AS03
Cohort 2: Group 10: SARS-CoV-2 vaccine HD
Cohort 2: Group 11: Placebo
Arm Description
Participants received a single intramuscular (IM) injection of SARS-CoV2 vaccine low-dose (LD) formulation along with adjuvant AF03 on Day 1.
Participants received a single IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1.
Participants received a single IM injection of SARS-CoV2 vaccine high-dose (HD) formulation along with adjuvant AF03 on Day 1.
Participants received a single IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1.
Participants received an IM injection of placebo matching to SARS-CoV2 vaccine on Day 1.
Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.
Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.
Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.
Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.
Participants received a single IM injection of SARS-CoV2 vaccine HD formulation without adjuvant on Day 1 and Day 22, respectively.
Participants received an IM injection of placebo matching to SARS-CoV2 on Day 1 and Day 22, respectively.
Outcomes
Primary Outcome Measures
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 1
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 22
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 36
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Geometric Mean Fold-rise (GMFR) of Serum Neutralization Antibody Titers at Day 22
SARS-CoV-2 neutralizing antibodies 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.
Geometric Mean Fold-rise of Serum Neutralization Antibody Titers at Day 36
SARS-CoV-2 neutralizing antibodies 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.
Number of Participants With >=2-fold and >=4-fold Rise in Serum Neutralization Antibody Titers at Day 22
SARS-CoV-2 neutralizing antibodies 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.
Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titer at Day 36
SARS-CoV-2 neutralizing antibodies 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
Seroconversion was defined as participants with a Baseline (Day 1) titer value below lower limit of quantification (LLOQ) with a detectable neutralization antibody titer above assay LLOQ post vaccination (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
Seroconversion was defined as participants with a Baseline (Day 1) titer value below LLOQ with a detectable neutralization antibody titer above assay LLOQ post vaccination (at Day 36). LLOQ of the neutralization assay was a titer of 10.
Number of Participants With Immediate Unsolicited Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the case report form (CRF) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Solicited Injection Site Reactions
A solicited reaction (SR) was defined as an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited injection site reactions included pain, erythema and swelling. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Solicited Systemic Reactions
An SR was defined as an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise and myalgia. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Unsolicited Adverse Events
An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Medically Attended Adverse Events (MAAE)
A MAAE were AEs with a new onset or a worsening of a condition that prompted the participant to seek unplanned medical advice at a physician's office (including phone contact or email) or emergency department. An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessarily had to have a causal relationship with treatment. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Serious Adverse Events (SAE)
An SAE was 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. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Adverse Events of Special Interest (AESIs)
An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. Reported AEs for each arm were presented as pre-specified in the study protocol.
Number of Participants With Laboratory Test Results Based on US FDA Toxicity Grading Guidance
Laboratory tests included hemoglobin (male and female), above and below normal white blood cell, lymphocytes, neutrophils & eosinophils, platelet count, creatinine and 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 in LFT), amylase & lipase, Urine: protein, glucose & blood. The US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adults and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" was used for grading. As per the guidance, Grade 1 = mild, Grade 2 = moderate and Grade 3 = severe.
Secondary Outcome Measures
Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 181, 202, 366 and 387
GMC of Anti-S binding antibodies were assessed using enzyme-linked immunosorbent assay (ELISA) and were measured in binding antibody units/milliliter (BAU/mL).
Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
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 01, Day 36/Day 01, Day 181/Day 1, Day 202/Day 1, Day 366/Day 1, and Day 387/Day 1.
Number of Participants With >=2-Fold and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
Binding Antibody Titers were evaluated by ELISA. Fold rise (2-fold and 4-fold) was calculated as the ratio of titer values for binding antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Day 22/Day 1 and Day 36/Day 1, Day 181/Day 1, Day 202/Day 1, Day 366/Day 1, and Day 387/Day 1.
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 181, 202, 366 and 387
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
SARS-CoV-2 neutralizing antibodies 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 181/Day 1 and Day 366/Day 1; Cohort 2: Day 202/Day 1 and Day 387/Day 1.
Number of Participants With 2-Fold and 4-Fold Rise in Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Cohort 1: Day 181/Day 1 and Day 366/Day 1 and Cohort 2: Day 202/Day 1 and Day 387/Day 1.
Percentage of Participants Achieving Seroconversion Against SARS-CoV2 Virus Antigens at Day 181, 202, 366 and 387
Seroconversion was defined as participants with a Baseline (Day 1) titer value below LLOQ with a detectable neutralization antibody titer above assay LLOQ post vaccination (Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387). LLOQ of the neutralization assay was a titer of 10.
Number of Participants With Virologically-confirmed Coronavirus Disease (COVID-19)-Like Illness
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. The various COVID-19-like illness symptoms were cough, fever, anosmia, ageusia, chillblains, difficulty breathing, shortness of breath, pneumonia, stroke, myocarditis, myocardial infarction, thromboembolic event, purpura fulminans, pharyngitis, chills, myalgia, headache, rhinorrhea, abdominal pain, nausea, diarrhea and vomiting.
Number of Participants With Serologically-confirmed SARS-CoV-2 Infection
Serologically-confirmed SARS-CoV-2 infection was defined as a change from negative to positive result in serum for presence of antibodies specific to non-Spike protein of SARS-CoV-2 detected by ELISA assay from any post-baseline sampling time point compared to the Baseline value.
Correlates of Risk / Protection Based on Antibody Responses to SARS-CoV-2
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.
Full Information
NCT ID
NCT04537208
First Posted
September 2, 2020
Last Updated
May 24, 2023
Sponsor
Sanofi Pasteur, a Sanofi Company
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT04537208
Brief Title
Study of Recombinant Protein Vaccine Formulations Against COVID-19 in Healthy Adults 18 Years of Age and Older
Official Title
Immunogenicity and Safety of SARS-CoV-2 Recombinant Protein Vaccine Formulations (With or Without Adjuvant) in Healthy Adults 18 Years of Age and Older
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
September 3, 2020 (Actual)
Primary Completion Date
November 19, 2021 (Actual)
Study Completion Date
November 19, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company
Collaborators
GlaxoSmithKline
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of the study were:
To describe the neutralizing antibody profile at Day 1, Day 22, and Day 36 of each study intervention group.
To describe the safety profile of all participants in each age group and each study intervention group up to 12 months post-last injection.
The secondary objectives of the study are:
To describe binding antibody profile at Day 1, Day 22, Day 36, Day 181 (Cohort 1) or Day 202 (Cohort 2), and Day 366 (Cohort 1) or Day 387 (Cohort 2) of each study intervention group.
To describe the neutralizing antibody profile at Day 181 (Cohort 1) or Day 202 (Cohort 2) and at Day 366 (Cohort 1) and Day 387 (Cohort 2) of each study intervention group.
To describe the occurrence of virologically-confirmed coronavirus disease (COVID-19)-like illness and serologically-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
To evaluate the correlation / association between antibody responses to SARS-CoV-2 Recombinant Protein and the risk of virologically-confirmed COVID-19-like illness and/or serologically-confirmed SARS-CoV-2 infection.
Detailed Description
The duration of each participant's participation in the study was approximately 365 days (Cohort 1) and 386 days (Cohort 2) post last injection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 (Healthy Volunteers)
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Model Description
This was a parallel group prevention study. Participants from 2 age groups (adults 18 through 49 years of age and adults 50 years of age and older) received either 1 injection (Cohort 1) or 2 injections (Cohort 2) of study vaccine or placebo control.
As a precautionary step, a sentinel safety cohort of 6 participants (younger adults only) within each dosing group from Cohort 1 was enrolled. An early safety data review was performed, including evaluation of safety data and laboratory measures to Day 9. Upon acceptable safety demonstrated from unblinded data review by limited members of the Sponsor Study Team, the remaining participants were enrolled simultaneously.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants, outcome assessors, Investigators, laboratory personnel, and the majority of Sponsor study staff will be blinded to vaccine group assignment; injection schedule will be unblinded and those preparing/administering the study interventions will be unblinded.
Allocation
Randomized
Enrollment
441 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1: Group 1: SARS-CoV-2 vaccine LD + AF03
Arm Type
Experimental
Arm Description
Participants received a single intramuscular (IM) injection of SARS-CoV2 vaccine low-dose (LD) formulation along with adjuvant AF03 on Day 1.
Arm Title
Cohort 1: Group 2: SARS-CoV-2 vaccine LD + AS03
Arm Type
Experimental
Arm Description
Participants received a single IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1.
Arm Title
Cohort 1: Group 3: SARS-CoV-2 vaccine HD + AF03
Arm Type
Experimental
Arm Description
Participants received a single IM injection of SARS-CoV2 vaccine high-dose (HD) formulation along with adjuvant AF03 on Day 1.
Arm Title
Cohort 1: Group 4: SARS-CoV-2 vaccine HD + AS03
Arm Type
Experimental
Arm Description
Participants received a single IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1.
Arm Title
Cohort 1: Group 5: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received an IM injection of placebo matching to SARS-CoV2 vaccine on Day 1.
Arm Title
Cohort 2: Group 6: SARS-CoV-2 vaccine LD + AF03
Arm Type
Experimental
Arm Description
Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.
Arm Title
Cohort 2: Group 7: SARS-CoV-2 vaccine LD + AS03
Arm Type
Experimental
Arm Description
Participants received IM injection of SARS-CoV2 vaccine LD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.
Arm Title
Cohort 2: Group 8: SARS-CoV-2 vaccine HD + AF03
Arm Type
Experimental
Arm Description
Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AF03 on Day 1 and Day 22, respectively.
Arm Title
Cohort 2: Group 9: SARS-CoV-2 vaccine HD + AS03
Arm Type
Experimental
Arm Description
Participants received IM injection of SARS-CoV2 vaccine HD formulation along with adjuvant AS03 on Day 1 and Day 22, respectively.
Arm Title
Cohort 2: Group 10: SARS-CoV-2 vaccine HD
Arm Type
Experimental
Arm Description
Participants received a single IM injection of SARS-CoV2 vaccine HD formulation without adjuvant on Day 1 and Day 22, respectively.
Arm Title
Cohort 2: Group 11: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received an IM injection of placebo matching to SARS-CoV2 on Day 1 and Day 22, respectively.
Intervention Type
Biological
Intervention Name(s)
CoV2 preS dTM-AF03 (low-dose)
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Intervention Type
Biological
Intervention Name(s)
CoV2 preS dTM-AF03 (high-dose)
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Intervention Type
Biological
Intervention Name(s)
CoV2 preS dTM-AS03 (low-dose)
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Intervention Type
Biological
Intervention Name(s)
CoV2 preS dTM-AS03 (high-dose)
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Intervention Type
Biological
Intervention Name(s)
CoV2 preS dTM (high-dose) without adjuvant
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Intervention Type
Biological
Intervention Name(s)
Placebo (0.9% normal saline)
Intervention Description
Pharmaceutical form: liquid; route of administration: intramuscular injection
Primary Outcome Measure Information:
Title
Geometric Mean Titers (GMTs) of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 1
Description
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Time Frame
Day 1 (pre-vaccination)
Title
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 22
Description
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Time Frame
Day 22 (post-vaccination)
Title
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 36
Description
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Time Frame
Day 36 (post-vaccination)
Title
Geometric Mean Fold-rise (GMFR) of Serum Neutralization Antibody Titers at Day 22
Description
SARS-CoV-2 neutralizing antibodies 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.
Time Frame
Day 1 (pre-vaccination) and Day 22 (post-vaccination)
Title
Geometric Mean Fold-rise of Serum Neutralization Antibody Titers at Day 36
Description
SARS-CoV-2 neutralizing antibodies 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.
Time Frame
Day 1 (pre-vaccination) and Day 36 (post-vaccination)
Title
Number of Participants With >=2-fold and >=4-fold Rise in Serum Neutralization Antibody Titers at Day 22
Description
SARS-CoV-2 neutralizing antibodies 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.
Time Frame
Day 1 (pre-vaccination) and Day 22 (post-vaccination)
Title
Number of Participants With >=2-Fold and >=4-Fold Rise in Serum Neutralization Antibody Titer at Day 36
Description
SARS-CoV-2 neutralizing antibodies 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.
Time Frame
Day 1 (pre-vaccination) and Day 36 (post-vaccination)
Title
Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 22
Description
Seroconversion was defined as participants with a Baseline (Day 1) titer value below lower limit of quantification (LLOQ) with a detectable neutralization antibody titer above assay LLOQ post vaccination (at Day 22). LLOQ of the neutralization assay was a titer of 10.
Time Frame
Day 22 (post-vaccination)
Title
Percentage of Participants Achieving Seroconversion Against SARS-CoV-2 Virus Antigens at Day 36
Description
Seroconversion was defined as participants with a Baseline (Day 1) titer value below LLOQ with a detectable neutralization antibody titer above assay LLOQ post vaccination (at Day 36). LLOQ of the neutralization assay was a titer of 10.
Time Frame
Day 36 (post-vaccination)
Title
Number of Participants With Immediate Unsolicited Adverse Events (AEs)
Description
An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the case report form (CRF) in terms of diagnosis and/or onset window post-vaccination. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRF. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
Within 30 minutes post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
Title
Number of Participants With Solicited Injection Site Reactions
Description
A solicited reaction (SR) was defined as an "expected" adverse reaction (AR) (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited injection site reactions included pain, erythema and swelling. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
Within 7 days post any and each vaccination (Vaccination 1 [i.e., at Day 1] and 2 [i.e., at Day 22])
Title
Number of Participants With Solicited Systemic Reactions
Description
An SR was defined as an "expected" AR (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise and myalgia. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
Within 7 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])
Title
Number of Participants With Unsolicited Adverse Events
Description
An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions of solicited reactions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
Within 21 days post any and each vaccination (Vaccination 1 [i.e., Day 1] and 2 [i.e., Day 22])
Title
Number of Participants With Medically Attended Adverse Events (MAAE)
Description
A MAAE were AEs with a new onset or a worsening of a condition that prompted the participant to seek unplanned medical advice at a physician's office (including phone contact or email) or emergency department. An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessarily had to have a causal relationship with treatment. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
Title
Number of Participants With Serious Adverse Events (SAE)
Description
An SAE was 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. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
Title
Number of Participants With Adverse Events of Special Interest (AESIs)
Description
An AESI (serious or non-serious) was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. Reported AEs for each arm were presented as pre-specified in the study protocol.
Time Frame
From Day 1 up to 12 months post last vaccination (i.e., up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2)
Title
Number of Participants With Laboratory Test Results Based on US FDA Toxicity Grading Guidance
Description
Laboratory tests included hemoglobin (male and female), above and below normal white blood cell, lymphocytes, neutrophils & eosinophils, platelet count, creatinine and 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 in LFT), amylase & lipase, Urine: protein, glucose & blood. The US FDA Guidance for Industry "Toxicity Grading Scale for Healthy Adults and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials" was used for grading. As per the guidance, Grade 1 = mild, Grade 2 = moderate and Grade 3 = severe.
Time Frame
From Day 1 up to 8 days post last dose (i.e., up to Day 9 for Cohort 1 and up to Day 30 for Cohort 2)
Secondary Outcome Measure Information:
Title
Geometric Mean Concentration (GMC) of Anti-S Binding Antibody at Day 1, 22, 36, 181, 202, 366 and 387
Description
GMC of Anti-S binding antibodies were assessed using enzyme-linked immunosorbent assay (ELISA) and were measured in binding antibody units/milliliter (BAU/mL).
Time Frame
Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
Title
Geometric Mean Fold-rise (GMFR) of Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
Description
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 01, Day 36/Day 01, Day 181/Day 1, Day 202/Day 1, Day 366/Day 1, and Day 387/Day 1.
Time Frame
Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
Title
Number of Participants With >=2-Fold and >=4- Fold Rise in Anti-S Binding Antibody Concentration at Day 22, 36, 181, 202, 366 and 387
Description
Binding Antibody Titers were evaluated by ELISA. Fold rise (2-fold and 4-fold) was calculated as the ratio of titer values for binding antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Day 22/Day 1 and Day 36/Day 1, Day 181/Day 1, Day 202/Day 1, Day 366/Day 1, and Day 387/Day 1.
Time Frame
Day 1 (pre-vaccination); Day 22 (post-vaccination), Day 36 (post-vaccination), Day 181 (only for Cohort 1), Day 202 (only for Cohort 2), Day 366 (only for Cohort 1), and Day 387 (only for Cohort 2)
Title
Geometric Mean Titers of Neutralizing Antibodies Against SARS-CoV-2 Recombinant Protein Vaccine Formulations at Day 181, 202, 366 and 387
Description
GMTs of SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. Titers were expressed in terms of 1/dilution.
Time Frame
Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
Title
Geometric Mean Fold-rise of Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
Description
SARS-CoV-2 neutralizing antibodies 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 181/Day 1 and Day 366/Day 1; Cohort 2: Day 202/Day 1 and Day 387/Day 1.
Time Frame
Day 1 (pre-vaccination), Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
Title
Number of Participants With 2-Fold and 4-Fold Rise in Serum Neutralization Antibody Titer at Day 181, 202, 366 and 387
Description
SARS-CoV-2 neutralizing antibodies was measured using a neutralization assay. The fold rise (2-fold and 4-fold) was calculated as the ratio of titer values of antibodies post-vaccination at specified timepoints and pre-vaccination (on Day 1) i.e., Cohort 1: Day 181/Day 1 and Day 366/Day 1 and Cohort 2: Day 202/Day 1 and Day 387/Day 1.
Time Frame
Day 1 (pre-vaccination), Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
Title
Percentage of Participants Achieving Seroconversion Against SARS-CoV2 Virus Antigens at Day 181, 202, 366 and 387
Description
Seroconversion was defined as participants with a Baseline (Day 1) titer value below LLOQ with a detectable neutralization antibody titer above assay LLOQ post vaccination (Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387). LLOQ of the neutralization assay was a titer of 10.
Time Frame
Cohort 1: Day 181 and Day 366 and Cohort 2: Day 202 and Day 387 (post-vaccination)
Title
Number of Participants With Virologically-confirmed Coronavirus Disease (COVID-19)-Like Illness
Description
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. The various COVID-19-like illness symptoms were cough, fever, anosmia, ageusia, chillblains, difficulty breathing, shortness of breath, pneumonia, stroke, myocarditis, myocardial infarction, thromboembolic event, purpura fulminans, pharyngitis, chills, myalgia, headache, rhinorrhea, abdominal pain, nausea, diarrhea and vomiting.
Time Frame
Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination)
Title
Number of Participants With Serologically-confirmed SARS-CoV-2 Infection
Description
Serologically-confirmed SARS-CoV-2 infection was defined as a change from negative to positive result in serum for presence of antibodies specific to non-Spike protein of SARS-CoV-2 detected by ELISA assay from any post-baseline sampling time point compared to the Baseline value.
Time Frame
Cohort 1: up to Day 366 (post-vaccination) and Cohort 2: up to Day 387 (post-vaccination)
Title
Correlates of Risk / Protection Based on Antibody Responses to SARS-CoV-2
Description
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.
Time Frame
From Day 1 up to Day 366 for Cohort 1 and up to Day 387 for Cohort 2
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Aged 18 years of age or older on the day of inclusion.
Informed consent form had been signed and dated.
Able to attend all scheduled visits and complied with all study procedures.
Exclusion Criteria:
Participant was pregnant, or lactating, or of childbearing potential and not used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 12 weeks after the last vaccination. To be considered of non-childbearing potential, a female was post-menopausal for at least 1 year or surgically sterile.
Receipt of any vaccine in the 30 days preceding the first study vaccination or planned receipt of any vaccine in the 30 days following the last study vaccination except for influenza vaccination, which might be received at least 2 weeks before and a minimum of 2 weeks after study vaccines.
Prior administration of a coronavirus vaccine SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome).
Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
History of SARS-CoV-2 infection, confirmed either clinically, serologically, or microbiologically
Chronic illness or condition considered to potentially increase the risk for severe COVID illness or that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.
Receipt of any therapy known to had in-vitro antiviral activity against SARS-CoV-2 within 72 hours prior to the first blood drew.
Health care workers provided direct participant care for COVID-19 participants.
The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi Pasteur, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 8400004
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Investigational Site Number 8400012
City
Rolling Hills Estates
State/Province
California
ZIP/Postal Code
90274
Country
United States
Facility Name
Investigational Site Number 8400011
City
Hollywood
State/Province
Florida
ZIP/Postal Code
33024
Country
United States
Facility Name
Investigational Site Number 8400019
City
Melbourne
State/Province
Florida
ZIP/Postal Code
32934
Country
United States
Facility Name
Investigational Site Number 8400016
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Investigational Site Number 8400002
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68134
Country
United States
Facility Name
Investigational Site Number 8400001
City
Rochester
State/Province
New York
ZIP/Postal Code
14609
Country
United States
Facility Name
Investigational Site Number 8400007
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Investigational Site Number 8400008
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44122
Country
United States
Facility Name
Investigational Site Number 8400003
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Investigational Site Number 8400014
City
Mount Pleasant
State/Province
South Carolina
ZIP/Postal Code
29464
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
Citations:
PubMed Identifier
35035955
Citation
De Rosa SC, Cohen KW, Bonaparte M, Fu B, Garg S, Gerard C, Goepfert PA, Huang Y, Larocque D, McElrath MJ, Morris D, Van der Most R, de Bruyn G, Pagnon A. Whole-blood cytokine secretion assay as a high-throughput alternative for assessing the cell-mediated immunity profile after two doses of an adjuvanted SARS-CoV-2 recombinant protein vaccine candidate. Clin Transl Immunology. 2022 Jan 11;11(1):e1360. doi: 10.1002/cti2.1360. eCollection 2022.
Results Reference
derived
PubMed Identifier
33887209
Citation
Goepfert PA, Fu B, Chabanon AL, Bonaparte MI, Davis MG, Essink BJ, Frank I, Haney O, Janosczyk H, Keefer MC, Koutsoukos M, Kimmel MA, Masotti R, Savarino SJ, Schuerman L, Schwartz H, Sher LD, Smith J, Tavares-Da-Silva F, Gurunathan S, DiazGranados CA, de Bruyn G. Safety and immunogenicity of SARS-CoV-2 recombinant protein vaccine formulations in healthy adults: interim results of a randomised, placebo-controlled, phase 1-2, dose-ranging study. Lancet Infect Dis. 2021 Sep;21(9):1257-1270. doi: 10.1016/S1473-3099(21)00147-X. Epub 2021 Apr 19. Erratum In: Lancet Infect Dis. 2022 Aug;22(8):e207.
Results Reference
derived
Learn more about this trial
Study of Recombinant Protein Vaccine Formulations Against COVID-19 in Healthy Adults 18 Years of Age and Older
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