Exploratory, First Time in Human (FTIH), Observer-blind, Randomized, Controlled Study to Evaluate Safety, Reactogenicity and Immunogenicity of Various Doses of GlaxoSmithKline Biologicals SA's (GSK) Investigational Omicron Variant S Glycoprotein (mRNA-CR-04) Vaccine When Administered Intramuscularly in Healthy Adults 18 to 49 Years of Age
Overview
- Phase
- Phase 1
- Intervention
- mRNA-CR-04 vaccine 10μg
- Conditions
- COVID-19
- Sponsor
- GlaxoSmithKline
- Enrollment
- 114
- Locations
- 1
- Primary Endpoint
- Number of Participants With Any Solicited Administration Site Events
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written or witnessed informed consent obtained from the participant prior to performance of any study-specific procedure.
- •Participants, who in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of the eDiary and study procedures).
- •Has received 2 doses of primary series and booster dose(s) of an authorized or licensed mRNA COVID-19 vaccine (only Moderna or Pfizer vaccines) with the last booster dose administered between at least 6 and 18 months or more prior to screening and has provided documentation of receiving the vaccination series (e.g., vaccination card).
- •Negative for SARS-CoV-2 infection by RT-PCR test at screening within 7 days prior to study vaccination.
- •Is a male or nonpregnant female of 18 to 49 years, inclusive, at screening.
- •If the participant is a woman of childbearing potential (WOCBP), the participant agrees to practice true abstinence or use at least 1 highly effective form of contraception for at least 30 days prior to study vaccination up to 1 month after study vaccination.
- •Agrees to refrain from blood or plasma donation from screening and up to 6 months after vaccination.
- •Is healthy or medically stable as determined by investigator judgment based on medical history, clinical laboratory tests, vital sign measurements, and physical examination findings.
Exclusion Criteria
- •Has a new onset, clinically significant, abnormal biochemistry or hematology finding \[defined as greater than or equal to (\>=) Grade 1\] at screening (participants with Grade 1 laboratory abnormalities that have been stable for at least 6 months before enrollment may be included in the study).
- •Has any medical disease or condition that, in the opinion of the investigator, precludes study participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of the trial.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •History of myocarditis, pericarditis, second- and third-degree heart block or idiopathic cardiomyopathy, or presence of any medical condition that increases risk of myocarditis or pericarditis, including cocaine abuse, cardiomyopathy, endomyocardial fibrosis, hypereosinophilic syndrome, hypersensitivity myocarditis eosinophilic granulomatosis with polyangiitis, persistent myocardial viral infection (e.g., due to enterovirus or adenovirus).
- •Has an acute febrile illness with a temperature \>=38.0 degree Celsius (°C) or \>=100.4 degree Fahrenheit (°F) observed by the participant or at the study site within 72 hours prior to study vaccination. Participants with suspected COVID-19 symptoms should be excluded and referred for medical care.
- •Has a history of hypersensitivity or severe allergic reaction, including anaphylaxis, generalized urticaria, angioedema, and other significant reactions to any previous vaccine, or any component of the study vaccine.
- •Has a body mass index greater than (\>) 40 Kilograms meter per square (kg/m\^2).
- •Has had known close contact with anyone who had a confirmed SARS-CoV-2 infection within 14 days before study vaccination.
- •Has a history of documented SARS-CoV-2 infection or COVID-19 within 6 months before the date of screening visit.
- •Has any self-reported or medically documented clinically significant medical or psychiatric condition. Significant medical conditions include, but are not limited to, the following:
Arms & Interventions
Part A, Group 1: mRNA CR-04 10 µg
Participants received mRNA 10 micrograms (µg) administered on Day 1.
Intervention: mRNA-CR-04 vaccine 10μg
Part A, Group 1: Placebo
Participants received placebo dose administered on Day 1.
Intervention: Placebo
Part A, Group 2: mRNA CR-04 30 µg
Participants received placebo dose administered on Day 1.
Intervention: mRNA-CR-04 vaccine 30μg
Part A, Group 2: Placebo
Participants received placebo dose administered on Day 1.
Intervention: Placebo
Part A, Group 3: mRNA CR-04 100 µg
Participants received mRNA 100 µg administered on Day 1
Intervention: mRNA-CR-04 vaccine 100μg
Part A, Group 3: Placebo
Participants received placebo dose administered on Day 1.
Intervention: Placebo
Part B: mRNA CR-04 3 µg
Participants received mRNA 3 µg administered on Day 1.
Intervention: mRNA-CR-04 vaccine 3μg
Part B: mRNA CR-04 10 µg
Participants received mRNA 10 µg administered on Day 1.
Intervention: mRNA-CR-04 vaccine 10μg
Part B: Placebo
Participants received placebo dose administered on Day 1.
Intervention: Placebo
Outcomes
Primary Outcomes
Number of Participants With Any Solicited Administration Site Events
Time Frame: Day 1 to Day 7
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.
Number of Participants With Any Solicited Systemic Events
Time Frame: Day 1 to Day 7
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.
Number of Participants With Any Unsolicited Adverse Events (AEs)
Time Frame: Day 1 to Day 30
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.
Number of Participants With Any Hematological and Biochemical Laboratory Abnormalities
Time Frame: Day 1 to Day 15
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.
Number of Participants With Any Medically Attended Adverse Events (MAAEs)
Time Frame: Day 1 to Day 31
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.
Number of Participants With Any Serious Adverse Events (SAEs)
Time Frame: Day 1 to Day 31
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.
Number of Participants With Any Adverse Events of Special Interest (AESIs)
Time Frame: Day 1 to Day 31
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.
Secondary Outcomes
- Number of Participants With Any MAAEs(Throughout the study period (Day 1 to Month 6))
- Number of Participants With Any SAEs(Throughout the study period (Day 1 to Month 6))
- Number of Participants With Any AESIs(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(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(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(At Days 15 and 31, and at Month 6 (compared with baseline [Day 1]))