The purpose of this study is to evaluate the safety, reactogenicity and immune responses of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA-CR-04 vaccine construct when administered in healthy adults previously vaccinated with SARS-CoV-2 mRNA vaccines.
There will be dose-escalation in part A of the study with sentinel dosing strategy implemented in each of 3 dosing levels (Group 1; 2; 3). At start, enrollment in Group 1 and 2 will occur simultaneously with the enrolment of 1st participant in Group 1. Each group will consist of 8 sentinel participants, with 6 receiving the mRNA-CR-04 vaccine and 2 receiving a placebo. The safety data from the sentinel participants in both groups, up to Day 8 post-vaccination, will be reviewed by the Internal Safety Review Committee (iSRC). If no safety signal is observed, vaccination of the non-sentinel participants in that group will continue. If there are no safety signals observed from the sentinel participants in Group 1 and Group 2, the enrollment and vaccination of the sentinel participants in Group 3 will begin. Part B of the study will commence only after all Part A participants have completed their Day 15 study visits and the Day 15 interim analysis is completed. In Part B, 2 doses of the mRNA-CR-04 vaccine will be evaluated.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
114
mRNA CR-04 vaccine, 10 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.
mRNA CR-04 vaccine, 30 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.
mRNA CR-04 vaccine, 100 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.
GSK Investigational Site
San Diego, California, United States
GSK Investigational Site
Melbourne, Florida, United States
GSK Investigational Site
Peoria, Illinois, United States
GSK Investigational Site
Austin, Texas, United States
Number of Participants With Any Solicited Administration Site Events
The solicited administration site events are pain, redness, swelling and lymphadenopathy (axillary swelling/ tenderness on the same side of the body as the site of injection). Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 7
Number of Participants With Any Solicited Systemic Events
The solicited systemic events are fever, headache, myalgia (muscle pain), arthralgia (joint pain), fatigue (tiredness), chills, abdominal pain, vomiting and diarrhea. Fever is defined as body temperature ≥38ºC; preferred location for measuring the temperature is oral. Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 7
Number of Participants With Any Unsolicited Adverse Events (AEs)
An unsolicited AE is an AE that is either not included in the list of solicited events or can be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. Unsolicited AEs include both serious and nonserious AEs. Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 30
Number of Participants With Any Hematological and Biochemical Laboratory Abnormalities
The hematological and biochemical parameters included alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), total bilirubin, creatinine, direct bilirubin, basophils, eosinophils increase, erytrocytes, hemoglobin decrease, lymphocytes decrease, mean corpuscular hemoglobin, mean corpuscular volume, monocytes, neutrophils decrease, platelets decrease, white blood cells (WBC) increase. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.
Time frame: Day 1 to Day 15
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Placebo is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.
mRNA CR-04 vaccine, 3 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.
Number of Participants With Any Medically Attended Adverse Events (MAAEs)
A MAAE is an AE for which the participant received medical attention including any symptom or illness requiring hospitalization, or an emergency room visit, or visit to/by a healthcare professional. Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 31
Number of Participants With Any Serious Adverse Events (SAEs)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 31
Number of Participants With Any Adverse Events of Special Interest (AESIs)
AESIs include potential immune-mediated diseases (pIMDs) which are autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology, myocarditis, and pericarditis, virologically confirmed COVID-19 cases, anaphylaxis, or severe hypersensitivity within 24 hours after study investigational product administration. Any = occurrence of the event regardless of intensity grade.
Time frame: Day 1 to Day 31
Number of Participants With Any MAAEs
A MAAE is an AE for which the participant received medical attention including any symptom or illness requiring hospitalization, or an emergency room visit, or visit to/by a healthcare professional. Any = occurrence of the event regardless of intensity grade.
Time frame: Throughout the study period (Day 1 to Month 6)
Number of Participants With Any SAEs
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, abnormal pregnancy outcome or any other situation as determined by the investigator. Any = occurrence of the event regardless of intensity grade.
Time frame: Throughout the study period (Day 1 to Month 6)
Number of Participants With Any AESIs
AESIs include potential immune-mediated diseases (pIMDs) which are autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology, myocarditis, and pericarditis, virologically confirmed COVID-19 cases, anaphylaxis, or severe hypersensitivity within 24 hours after study investigational product administration. Any = occurrence of the event regardless of intensity grade.
Time frame: Throughout the study period (Day 1 to Month 6)
Geometric Mean Titers (GMT) of Neutralizing Titers Against Pseudovirus Bearing S Protein From Vaccine Encoded SARS-CoV-2 and Wild Type (WT) Strains
The analyzed neutralizing titers were SARS-CoV-2 Neutralizing Titer BA.5 and SARS-CoV-2 Neutralizing Titer D614G. D= Day; M= Month.
Time frame: At Days 1, 15 and 31, and at Month 6
Geometric Mean Ratio (GMR) of Neutralizing Titers Against Pseudovirus Bearing S Protein From Vaccine Encoded SARS-CoV-2 and WT Strains
The analyzed neutralizing titers were SARS-CoV-2 Neutralizing Titer BA.5 and SARS-CoV-2 Neutralizing Titer D614G. D= Day; M= Month.
Time frame: At Days 15 and 31, and at Month 6 (compared with baseline [Day 1])
Number of Participants With Vaccine Response Rate (VRR) Based on Neutralizing Titers Against Vaccine Encoded SARS-CoV-2 and WT Strains
VRR is expressed as the number of participants with a vaccine response, defined as at least a 4-fold greater neutralizing titer as compared to the titer at Day 1. D= Day; M= Month.
Time frame: At Days 15 and 31, and at Month 6 (compared with baseline [Day 1])