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

NCT04758962 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 214525
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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 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

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (8)

• 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

  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

  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

  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

  At Day 8, Day 15, Day 38 and Day 45

Study Arms (1)

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.

Biological: 1 µg CoV2 SAM (LNP)

Interventions

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.

CoV-2 SAM [LNP] Group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Diabetes mellitus (type I or II), with exception of gestational diabetes.
• Respiratory disease such as:

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Rochester, New York, 14609, United States

Location

Related Publications (1)

• 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.

  PMID: 34990810 DERIVED

MeSH Terms

Conditions

Virus Diseases

Condition Hierarchy (Ancestors)

Infections

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: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2021
• First Posted: February 17, 2021
• Study Start: February 15, 2021
• Primary Completion: June 4, 2021
• Study Completion: April 19, 2022
• Last Updated: August 24, 2026
• Results First Posted: August 24, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

US (1)