A Safety and Immune Response Study to Evaluate Varying Doses of an mRNA Vaccine Against Coronavirus Disease 2019 (COVID-19) in Healthy Adults

NCT05972993 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 219112
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 4

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.

Conditions

COVID-19

Keywords

COVID-19; SARS-CoV-2; Master Protocol; Omicron; mRNA

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  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.

  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.

  Day 1 to Day 15

• 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.

  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.

  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.

  Day 1 to Day 31

Secondary Outcomes (6)

• 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])

Study Arms (9)

Part A, Group 1: mRNA CR-04 10 µg

EXPERIMENTAL

Participants received mRNA 10 micrograms (µg) administered on Day 1.

Biological: mRNA-CR-04 vaccine 10μg

Part A, Group 1: Placebo

PLACEBO COMPARATOR

Participants received placebo dose administered on Day 1.

Drug: Placebo

Part A, Group 2: mRNA CR-04 30 µg

EXPERIMENTAL

Participants received placebo dose administered on Day 1.

Biological: mRNA-CR-04 vaccine 30μg

Part A, Group 2: Placebo

PLACEBO COMPARATOR

Participants received placebo dose administered on Day 1.

Drug: Placebo

Part A, Group 3: mRNA CR-04 100 µg

EXPERIMENTAL

Participants received mRNA 100 µg administered on Day 1

Biological: mRNA-CR-04 vaccine 100μg

Part A, Group 3: Placebo

PLACEBO COMPARATOR

Participants received placebo dose administered on Day 1.

Drug: Placebo

Part B: mRNA CR-04 3 µg

EXPERIMENTAL

Participants received mRNA 3 µg administered on Day 1.

Biological: mRNA-CR-04 vaccine 3μg

Part B: mRNA CR-04 10 µg

EXPERIMENTAL

Participants received mRNA 10 µg administered on Day 1.

Biological: mRNA-CR-04 vaccine 10μg

Part B: Placebo

PLACEBO COMPARATOR

Participants received placebo dose administered on Day 1.

Drug: Placebo

Interventions

mRNA-CR-04 vaccine 10μg BIOLOGICAL

mRNA CR-04 vaccine, 10 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.

Part A, Group 1: mRNA CR-04 10 µg; Part B: mRNA CR-04 10 µg

mRNA-CR-04 vaccine 30μg BIOLOGICAL

mRNA CR-04 vaccine, 30 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.

Part A, Group 2: mRNA CR-04 30 µg

mRNA-CR-04 vaccine 100μg BIOLOGICAL

mRNA CR-04 vaccine, 100 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.

Part A, Group 3: mRNA CR-04 100 µg

Placebo DRUG

Placebo is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.

Part A, Group 1: Placebo; Part A, Group 2: Placebo; Part A, Group 3: Placebo; Part B: Placebo

mRNA-CR-04 vaccine 3μg BIOLOGICAL

mRNA CR-04 vaccine, 3 µg, is administered intramuscularly into the deltoid muscle of the non-dominant arm on day 1.

Part B: mRNA CR-04 3 µg

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Moderate or severe respiratory disease (e.g., chronic obstructive pulmonary disease, asthma).
• Uncontrolled hypertension, defined as an average systolic blood pressure \>= 140 millimeters of mercury (mmHg) or an average diastolic blood pressure \>= 90 mmHg, based on an average of up to 3 blood pressure measurements.
• Clinically significant cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease).
• Neurological or neurodevelopmental conditions (e.g., Down syndrome, dementia, chronic migraine not controlled by medication, epilepsy, stroke or seizures in the last 3 years, encephalopathy, focal neurologic deficits, Guillain- Barré syndrome, encephalomyelitis, or transverse myelitis).
• Ongoing malignancy or recent diagnosis of malignancy in the last 5 years (excluding basal cell and squamous cell carcinoma of the skin).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

San Diego, California, 92108, United States

Location

GSK Investigational Site

Melbourne, Florida, 32934, United States

Location

GSK Investigational Site

Peoria, Illinois, 61614, United States

Location

GSK Investigational Site

Austin, Texas, 78705, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Data will be collected in an observer-blind manner.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation with sentinel dosing.

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 2, 2023
• Study Start: August 7, 2023
• Primary Completion: May 9, 2024
• Study Completion: October 14, 2024
• Last Updated: May 28, 2025
• Results First Posted: May 28, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (4)