A Study of the Safety of and Immune Response to Varying Doses of a Vaccine Against COVID-19 in Healthy Adults

A Phase I, First-Time-in Human (FTiH), Open-label, Dose Escalation, Non-randomized Study to Assess Safety, Reactogenicity and Immune Response of a CoV-2 SAM (LNP) Vaccine When Administered Intramuscularly on a 0, 1 Month Schedule in Healthy Adults 18 to 50 Years of Age

The purpose of this study is to assess the safety, reactogenicity and immune response of a self-amplifying mRNA (SAM) lipid nanoparticle (LNP) platform with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike antigen (CoV-2 SAM [LNP] vaccine) in ascending doses when administered intramuscularly (IM) on a 0,1-month schedule to healthy adults 18 to 50 years of age. There will be no administration of escalated doses of the study vaccine.

Study Overview

• Status: Completed
• Conditions: Virus Diseases
• Intervention / Treatment: Biological: 1 µg CoV2 SAM (LNP)

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14609
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
• Written or thumb printed informed consent obtained from the participant prior to performance of any study specific procedure.
• Healthy participants as established by medical history and clinical examination before entering into the study.
• A male or female between, and including, 18 and 50 years of age at the time of first study intervention administration.
• Body Mass Index>18 Kg/m^2 and <30 Kg/m^2.
• Participants with following hematological/biochemical parameters:
• White Blood Cells within the study designated laboratory normal range. Participants with FDA toxicity grade 1 differential cell counts and considered not clinically significant may be enrolled at the discretion of the investigator, and with the review and approval of the medical monitor.
• Platelets = 125,000 - 500,000 cells/mm^3.
• Hemoglobin within normal range of the study designated laboratory.
• Alanine aminotransferase within the study designated laboratory normal range.
• Aspartate aminotransferase within the study designated laboratory normal range Total bilirubin within the study designated laboratory normal range.
• Alkaline phosphatase within the study designated laboratory normal range.
• Blood urea nitrogen within the study designated laboratory normal range.
• Serum creatinine less than or equal to 1.1 times study designated laboratory's upper limit of normal.
• Seronegative for hepatitis B surface antigen, hepatitis C virus antibodies, or human immunodeficiency virus antibodies.
• Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
• Female participants of childbearing potential may be enrolled in the study, if the participant:
• has practiced adequate contraception for 1 month prior to study intervention administration, and,
• has a negative pregnancy test on the day of study intervention administration, and,
• has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the study intervention administration series.

Exclusion Criteria:

Medical conditions

• Individuals with signs and symptoms consistent with COVID-19, according to CDC guidelines and following clinical judgement.
• Nasal and/or oral swab positive for SARS-CoV-2 by RT-PCR within the last 30 days, unless participant has had a subsequent negative swab and is asymptomatic.
• Close contact (within 30 days prior to study intervention administration) with anyone known to have SARS-CoV-2 infection.
• Individuals currently working in occupations with high risk of exposure to SARS-CoV-2 (e.g., healthcare workers, emergency response personnel).
• Any confirmed or suspected immunosuppressive/immunodeficient condition based on medical history and physical examination.
• Family history of congenital/hereditary immunodeficiency.
• History of or current autoimmune disease.
• History of any reaction/hypersensitivity likely to be exacerbated by any components of the study intervention.
• History of hypersensitivity/severe allergic reaction to any previous licensed/unlicensed vaccine.
• Lymphoproliferative disorder/malignancy within previous 5 years (excluding effectively treated non-melanotic skin cancer).
• History of recurrent anemia within the last 6 months.
• Hypersensitivity to latex.
• Any acute/chronic, clinically significant disease The following conditions will be exclusionary:
• Diabetes mellitus (type I or II), with exception of gestational diabetes.
• Respiratory disease such as:
• Chronic Pulmonary diseases,
• Bronchopulmonary dysplasia,
• Uncontrolled asthma/asthma necessitating treatment with chronic systemic/inhaled glucocorticoids.
• Significant and/or uncontrolled psychiatric illness:
• hospitalization for psychiatric illness, history of suicide attempts/confinement for danger to self/others within 5 years,
• clinically significant depression.
• Major neurological disease including:
• seizure or adulthood epilepsy (note: history of febrile convulsion in childhood is not exclusionary),
• myasthenia gravis,
• history of repetitive migraine mal/status migrainosus.
• Significant cardiovascular disease, including:
• Uncontrolled arterial hypertension,
• Congenital heart disease,
• Previous myocardial infarction,
• Valvular heart disease or history of rheumatic fever,
• Previous bacterial endocarditis,
• History of cardiac surgery,
• Personal/ family history of cardiomyopathy/sudden adult death.
• Asplenia, functional asplenia/any condition resulting in the absence/removal of the spleen.
• Hereditary angioedema, acquired angioedema/ idiopathic forms of angioedema.
• History of, or concurrent, autoimmune thyroid disease regardless of treatment and thyroid status as well as any uncontrolled thyroid disease.
• Idiopathic urticaria within the past year.
• Any other significant uncontrolled medical illness within 3 months prior to study intervention administration.
• Acute illness and/or fever at the time of screening. Participants with acute illness and/ or fever at the time of screening may be re screened later.
• Participants with a minor illness without fever may be enrolled.
• Any other clinical condition that might pose additional risk to the participant due to participation in the study.

Prior/Concomitant therapy

• Use of any investigational or non-registered product other than the study intervention(s) during the period beginning 45 days before the first dose (Day -45 to Day 1), or their planned use during the study.
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the vaccination and ending 30 days after, with the exception of any licensed influenza vaccine which may be administered >15 days before/after vaccination.
• Planned administration/administration of an Emergency Use Authorization vaccine against SARS-CoV-2 in the period starting prior to the first dose of study intervention and ending 15 days after the second dose of study intervention
• Administration of long-acting immune-modifying drugs at any time during the study
• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose until study end.
• Chronic administration of immunosuppressants/other immune-modifying drugs during the period starting 6 months prior to the first dose. For corticosteroids, this will mean prednisone equivalent >10 mg/day. Topical steroids are allowed.

Prior/Concurrent clinical study experience

• Receipt of any other SARS-CoV-2 or other experimental coronavirus vaccine at any time prior to or during the study
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been/will be exposed to an investigational/a non-investigational intervention

Other exclusions

• Pregnant/lactating female
• Female planning to become pregnant/planning to discontinue contraceptive precautions
• Alcohol and/or drug abuse.
• Current/history of chronic tobacco/marijuana smoking/vaping.
• Participants with extensive tattoos covering deltoid region on both the arms that would preclude the assessment of local reactogenicity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CoV-2 SAM [LNP] Group; Participants received two 1-microgram (µg) doses of Coronavirus-2 Spike self-amplifying mRNA lipid nanoparticle (CoV-2 SAM [LNP]) vaccine, one at Day 1 and one at Day 31.	Biological: 1 µg CoV2 SAM (LNP); 2 doses of 1 µg CoV2 SAM (LNP) vaccine in 0,1-month schedule, administered IM in the deltoid of the non-dominant arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Solicited Administration Site Adverse Events After Each Vaccination	The solicited administration site adverse events assessed were pain, redness and swelling.	Within 7 days post each vaccination (vaccination at Day 1 and Day 31)
Number of Participants With Solicited Systemic Adverse Events After Each Vaccination	The solicited systemic events assessed were abdominal pain, arthralgia, diarrhea, fatigue, fever, headache, myalgia, nausea, vomiting. Fever is defined as temperature ≥38.0°Celsius (C)/100.4°Fahrenheit (F) regardless the location of measurement.	Within 7 days post each vaccination (vaccination at Day 1 and Day 31)
Number of Participants With Unsolicited Adverse Events (AEs) After Each Vaccination	An unsolicited AE is defined as an AE that was not included in a list of solicited events using a Participant eDiary, or any solicited event with onset after the 7-day period post each vaccination.	Within 30 days post each vaccination (vaccination at Day 1 and Day 31)
Number of Participants With Hematological and Biochemical Laboratory Abnormalities at Day 2 Compared With Baseline (Day 1)	The hematological and biochemical laboratory parameters assessed include alanine aminotransferase (ALT),alkaline phosphatase (ALP),aspartate aminotransferase (AST),bilirubin,creatinine,urea nitrogen,eosinophils,erythrocytes,hemoglobin,leukocytes,lymphocytes,neutrophils,partial thromboplastin time (PTT) and platelets. Categories reported for each parameter when comparing Day 1 baseline and post-baseline hematological and biochemical laboratory results are defined as follows:<range at baseline [Day 1]>, <range at post-baseline time point> for example, Below-Within, where each range is classified as below, within, or above the applicable laboratory reference range. 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 2 compared to baseline (Day 1)
Number of Participants With Hematological and Biochemical Laboratory Abnormalities at Day 8 Compared With Baseline (Day 1)	The hematological and biochemical laboratory parameters assessed include ALT, ALP, AST, bilirubin, creatinine, urea nitrogen, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, neutrophils, PTT and platelets. Categories reported for each parameter when comparing Day 1 (baseline) and post-baseline hematological and biochemical laboratory results are defined as follows: <range at baseline [Day 1]>, <range at post-baseline time point> for example, Below-Within, where each range is classified as below, within, or above the applicable laboratory reference range. 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; Unknown = No results are available for the specified visit and laboratory parameter.	Day 8 compared to baseline (Day 1)
Number of Participants With Hematological and Biochemical Laboratory Abnormalities at Day 31 Compared With Baseline (Day 1)	The hematological and biochemical laboratory parameters assessed include ALT, ALP, AST, bilirubin, creatinine, urea nitrogen, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, neutrophils, PTT and platelets. Categories reported for each parameter when comparing Day 1 (baseline) and post-baseline hematological and biochemical laboratory results are defined as follows: <range at baseline [Day 1]>, <range at post-baseline time point> for example, Below-Within, where each range is classified as below, within, or above the applicable laboratory reference range. 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; Unknown = No results are available for the specified visit and laboratory parameter.	Day 31 compared to baseline (Day 1)
Number of Participants With Hematological and Biochemical Laboratory Abnormalities at Day 32 Compared With Baseline (Day 1)	The hematological and biochemical laboratory parameters assessed include ALT, ALP, AST, bilirubin, creatinine, urea nitrogen, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, neutrophils, PTT and platelets. Categories reported for each parameter when comparing Day 1 (baseline) and post-baseline hematological and biochemical laboratory results are defined as follows: <range at baseline [Day 1]>, <range at post-baseline time point> for example, Below-Within, where each range is classified as below, within, or above the applicable laboratory reference range. 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; Unknown = No results are available for the specified visit and laboratory parameter.	Day 32 compared to baseline (Day 1)
Number of Participants With Hematological and Biochemical Laboratory Abnormalities at Day 38 Compared With Baseline (Day 1)	The hematological and biochemical laboratory parameters assessed include ALT, ALP, AST, bilirubin, creatinine, urea nitrogen, eosinophils, erythrocytes, hemoglobin, leukocytes, lymphocytes, neutrophils, PTT and platelets. Categories reported for each parameter when comparing Day 1 (baseline) and post-baseline hematological and biochemical laboratory results are defined as follows: <range at baseline [Day 1]>, <range at post-baseline time point> for example, Below-Within, where each range is classified as below, within, or above the applicable laboratory reference range. 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; Unknown = No results are available for the specified visit and laboratory parameter.	Day 38 compared to baseline (Day 1)
Number of Participants With Medically-attended AEs (MAEs) From Day 1 to Day 61	A medically attended adverse event (MAE) is defined as an AE for which the participant received medical attention defined as hospitalization, an emergency room visit or a visit to or from medical personnel (i.e., nurse practitioner or physician assistant or medical doctor) for any reason.	Day 1 to Day 61
Number of Participants With Serious AEs (SAEs) From Day 1 to Day 61	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 disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgment.	Day 1 to Day 61
Number of Participants With Adverse Events of Special Interest (AESIs) [Potential Immune-mediated Diseases (pIMDs) and COVID-19 Cases) From Day 1 to Day 61	AESIs assessed include pIMDs and COVID-19 cases. pIMDs are a subset of AESIs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology. Any suspected, probable or confirmed case of COVID-19 was reported.	Day 1 to Day 61

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With MAEs, SAEs and AESIs (pIMDs and COVID-19 Cases) From Day 1 up to Day 391		Day 1 to Day 391
Percentage of Participants With Anti-Spike (S) Immunoglobulin G (IgG) Antibody Concentrations at Day 1, Day 31 and Day 61	Anti-S IgG antibody concentrations were measured using Enzyme-linked Immunosorbent Assay (ELISA). The considered cut-off value for this analysis was greater than or equal (>=) 50.3 ELISA units per milliliter (EU/mL).	At pre-vaccination on Day 1 and Day 31, and at Day 61
Number of Participants With Anti-Nucleocapsid (N) IgG Antibody Concentrations at Day 1, Day 31 and Day 61	Anti-N IgG antibody concentrations were measured using ELISA. The considered cut-off value for this analysis was >=47.6 EU/mL.	At pre-vaccination on Day 1 and Day 31, and at Day 61
SARS-CoV-2 Neutralizing Antibody Titers by Live Wild-Type Virus Neutralization at Day 1, Day 31 and Day 61	Neutralizing antibodies against SARS-CoV-2 were measured in serum using a live wild-type virus neutralizing assay and expressed as geometric mean titers (GMT).	At pre-vaccination on Day 1 and Day 31, and at Day 61
Percentage of Participants With Anti-S IgG Antibody Concentrations at Day 8, Day 15, Day 38 and Day 45	Anti-S IgG antibody concentrations were measured using ELISA. The considered cut-off value for this analysis was >= 50.3 EU/mL.	At Day 8, Day 15, Day 38 and Day 45
Number of Participants With Anti-N IgG Antibody Concentrations at Day 8, Day 15, Day 38 and Day 45	Anti-N IgG antibody concentrations were measured using ELISA. The considered cut-off value for this analysis was >=47.6 EU/mL.	Day 8, Day 15, Day 38 and Day 45
Cell Mediated Immune (CMI) Response in Terms of Frequency of SARS-CoV-2 Spike-specific Cluster of Differentiation (CD) 4+ T-cells Secreting at Least 2 Markers Including One Cytokine	Frequency of SARS-CoV-2 Spike-specific CD4+ T-cells expressing at least 2 activation markers including at least 1 cytokine (among IL-2, IFN gamma, TNF alpha, IL-13, IL-17, 4-1BB and CD40L) was determined by flow cytometry using intracellular cytokine staining (ICS) and expressed as CD4+ T-cells per million cells (CD4+ T-cells/million cells).	Pre-vaccination on Day 1 and Day 31, and at Day 61
CMI Response in Terms of Frequency of SARS-CoV-2 Spike-specific CD 8+ T-cells Secreting at Least 2 Markers Including One Cytokine	Frequency of SARS-CoV-2 Spike-specific CD8+ T-cells expressing at least 2 activation markers including at least 1 cytokine (among IL-2, IFN gamma, TNF alpha, IL-13, IL-17, 4-1BB and CD40L) was determined by flow cytometry using intracellular cytokine staining (ICS) and expressed as CD8+ T-cells/million cells.	Pre-vaccination on Day 1 and Day 31, and at Day 61

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Maruggi G, Mallett CP, Westerbeck JW, Chen T, Lofano G, Friedrich K, Qu L, Sun JT, McAuliffe J, Kanitkar A, Arrildt KT, Wang KF, McBee I, McCoy D, Terry R, Rowles A, Abrahim MA, Ringenberg MA, Gains MJ, Spickler C, Xie X, Zou J, Shi PY, Dutt T, Henao-Tamayo M, Ragan I, Bowen RA, Johnson R, Nuti S, Luisi K, Ulmer JB, Steff AM, Jalah R, Bertholet S, Stokes AH, Yu D. A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models. Mol Ther. 2022 May 4;30(5):1897-1912. doi: 10.1016/j.ymthe.2022.01.001. Epub 2022 Jan 3.

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Actual): June 4, 2021
• Study Completion (Actual): April 19, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 16, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2026
• Last Update Submitted That Met QC Criteria: July 3, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Virus Diseases
• Other Study ID Numbers: 214525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://d3l8i7lo48obsd.cloudfront.net/gsk-patient-level-data-sharing-july2025-1-Bgwa1UthxvluYbWYTThw.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No