Virus DiseasesPhase 1NCT04758962
A Study of the Safety of and Immune Response to Varying Doses of a Vaccine Against COVID-19 in Healthy Adults
A Phase 1 study testing 1 µg CoV2 SAM (LNP) in people with Virus Diseases, run by GlaxoSmithKline at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Virus Diseases
- What is being tested?
- 1 µg CoV2 SAM (LNP)
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Feb 2021to 19 Apr 2022
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
- Conditions
- Virus Diseases
- Being tested
- 1 µg CoV2 SAM (LNP)
- Medical subject headings
- Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1 µg CoV2 SAM (LNP)Biological
2 doses of 1 µg CoV2 SAM (LNP) vaccine in 0,1-month schedule, administered IM in the deltoid of the non-dominant arm.
| Study group | Role | What they receive |
|---|---|---|
| CoV-2 SAM [LNP] Group | Experimental | 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. Receives: Biological: 1 µg CoV2 SAM (LNP) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Solicited Administration Site Adverse Events After Each Vaccination
The solicited administration site adverse events assessed were pain, redness and swelling.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 1 to Day 61
Secondary outcomes (8)
Number of Participants With MAEs, SAEs and AESIs (pIMDs and COVID-19 Cases) From Day 1 up to Day 391
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: Pre-vaccination on Day 1 and Day 31, and at Day 61
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2021
- Study start15 Feb 2021
- Primary completion4 Jun 2021
- Study completion19 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Virus DiseasesStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04758962
- Sponsor's protocol ID
- 214525
- Status last verified
- Jul 2026
- First submitted
- 8 Feb 2021
- Last updated
- 24 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
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.
PubMed 34990810