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 FDA Drug

• 1 other identifier: 214525
• Study Type: interventional
• Target: 40
• 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 (16)

• Number of participants with at least 1 solicited administration site event during 7-day follow-up period after first vaccination (first vaccination occurs on Day 1)

  The solicited administration site events are pain, redness and swelling.

  7-day follow-up period after first vaccination (from Day 1 to Day 7)

• Number of participants with at least 1 solicited administration site event during 7-day follow-up period after second vaccination (second vaccination occurs on Day 31)

  The solicited administration site events are pain, redness and swelling.

  7-day follow-up period after second vaccination (from Day 31 to Day 37)

• Number of participants with at least 1 solicited systemic event during 7-day follow-up period after first vaccination (first vaccination occurs on Day 1)

  The solicited systemic events are fatigue, fever, nausea, vomiting, diarrhea, abdominal pain, headache, myalgia and arthralgia.

  7-day follow-up period after first vaccination (from Day 1 to Day 7)

• Number of participants with at least 1 solicited systemic event during 7-day follow-up period after second vaccination (second vaccination occurs on Day 31)

  The solicited systemic events are fatigue, fever, nausea, vomiting, diarrhea, abdominal pain, headache, myalgia and arthralgia.

  7-day follow-up period after second vaccination (from Day 31 to Day 37)

• Number of participants with any unsolicited adverse event (AE) during 30-day follow-up period after first vaccination (first vaccination occurs on Day 1)

  An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include both serious and non-serious AEs.

  30-day follow-up period after first vaccination (from Day 1 to Day 30)

• Number of participants with any unsolicited AE during 30-day follow-up period after second vaccination (second vaccination occurs on Day 31)

  An unsolicited AE is an AE that was not included in a list of solicited events using a Participant Diary. Unsolicited events must have been spontaneously communicated by a participant who has signed the informed consent. Unsolicited AEs include both serious and non-serious AEs.

  30-day follow-up period after second vaccination (from Day 31 to Day 60)

• Number of participants with any hematological and biochemical laboratory abnormality at screening

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Screening

• Number of participants with any hematological and biochemical laboratory abnormality at Day 1

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 1

• Number of participants with any hematological and biochemical laboratory abnormality at Day 2

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 2

• Number of participants with any hematological and biochemical laboratory abnormality at Day 8

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 8

• Number of participants with any hematological and biochemical laboratory abnormality at Day 31

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 31

• Number of participants with any hematological and biochemical laboratory abnormality at Day 32

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 32

• Number of participants with any hematological and biochemical laboratory abnormality at Day 38

  Clinically significant abnormal laboratory findings are those which are not associated with an underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Hematology and biochemistry results below or above the laboratory normal ranges were evaluated for the following parameters: Hematology: platelet count, red blood cell (RBC) count, hemoglobin, white blood cell (WBC) count with differential neutrophils, lymphocytes and eosinophils. Biochemistry: blood urea nitrogen (BUN), creatinine, liver function tests - alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase and bilirubin.

  At Day 38

• Number of participants with at least 1 medically attended AE (MAE) from first administered dose up to 30 days after last dose (second vaccination occurs on Day 31)

  A MAE is an AE for which the participants received medical attention defined as hospitalization, or an otherwise unscheduled visit to or from medical personnel for any reason, including emergency room visits.

  From Day 1 to Day 60

• Number of participants with at least 1 serious adverse event (SAE) from first administered dose up to 30 days after last dose (second vaccination occurs on Day 31)

  An SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient.

  From Day 1 to Day 60

• Number of participants with at least 1 adverse event of special interest (AESI) from first administered dose up to 30 days after last dose (second vaccination occurs on Day 31)

  Potential immune-mediated diseases (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. Other AESIs are COVID-19 cases (any suspected, probable or confirmed case of COVID-19 should be reported by the principal investigator as AESI, as defined by World Health Organization).

  From Day 1 to Day 60

Secondary Outcomes (23)

• Number of participants with at least 1 MAE from first administered dose up to study conclusion

  From Day 1 to Day 391

• Number of participants with at least 1 SAE from first administered dose up to study conclusion

  From Day 1 to Day 391

• Number of participants with at least 1 AESI from first administered dose up to study conclusion

  From Day 1 to Day 391

• Humoral immune response in terms of SARS-CoV-2 Anti-Spike immunoglobulin G (IgG) antibody geometric mean concentrations (GMCs) at pre-vaccination, first dose (first vaccination occurs on Day 1)

  At Day 1

• Humoral immune response in terms of SARS-CoV-2 Anti-Spike IgG antibody GMCs at pre-vaccination, second dose (second vaccination occurs on Day 31)

  At Day 31

Study Arms (1)

1 µg CoV2 SAM (LNP) Group

EXPERIMENTAL

Participants aged 18-50 years, allocated in the 1 µg COV2 SAM (LNP) Group receive 2 doses of 1 µg CoV2 SAM (LNP) vaccine 30 days apart, at day 1 and day 31 and are followed up until the study end.

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.

1 µg CoV2 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

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: January 18, 2024

Record last verified: 2024-01

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, 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 (1)