Study to Assess Safety, Reactogenicity and Immunogenicity of the repRNA(QTP104) Vaccine Against SARS-CoV-2(COVID-19)

A Phase 1, Dose-escalation, Multi-center, Open-label, Study to Evaluate the Safety, Reactogenicity and Immunogenicity of a Preventive SARS-CoV-2 Vaccine (QTP104) in Healthy Adults

This study is to evaluate the safety, reactogenicity, and immunogenicity of the QTP104 vaccine against SARS-CoV-2 infection in healthy adults.

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19; SARS-CoV-2
• Intervention / Treatment: Biological: QTP104 1ug; Biological: QTP104 5ug; Biological: QTP104 25ug

Detailed Description

This study is designed to evaluate the safety, immunogenicity of 3 doses of QTP104. The reason for including 3 doses were to further explore the immunogenicity of these dose levels. This clinical trial is an open label and does not apply to randomized assignment procedures. This study is an open label and does not apply to the maintenance and release procedure of double-blinding. The selection of healthy adults is to confirm the safety of dose-escalation through phase 1 clinical trials.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Adult male or female aged 19 to 55 years at the screening visit (Visit 1)
2. Subject with a Body Mass Index (BMI) of 18kg/m2 or more and 30kg/m2 or less at the screening visit (Visit 1)
3. Women of childbearing potential who have not undergone sterilization must agree to use an appropriate method of contraception* during this clinical trial period and up to 3 months after the end of administration of the investigational drug and there must be evidence of non-fertility at the screening visit (Visit 1)
4. Men who has not undergone a vasectomy must consent to the use of barrier contraception (i.e., condoms) and if both subejct and partner agree to use an appropriate method of contraception for the duration of the clinical trial and up to 6 months after the end of investigational drug administration
5. Subject who can collect blood and urine during this clinical trial period including the last visit
6. Subject who havs heard the detailed explanation of this clinical trial, have voluntarily decided to participate, and have agreed in writing to abide by the precautions
7. Subject who agrees not to donate blood or transfusion (including whole blood, plasma components, platelet components and platelet plasma components) during the clinical trial period

Exclusion Criteria:

[Current disease and medical history]

1. Subject who has identified any acute, chronic, or clinically significant disease as a result of a physical or laboratory examination during a screening visit (Visit 1)
2. Subject who has a history of malignant tumors within the past 5 years
3. Subject who has an immune dysfunction, including immunodeficiency disease, or a family history thereof through a medical history and/or physical examination
4. Subject who has positive SARS-CoV-2 IgG Ab results during screening visit (Visit 1)
5. Subject previously diagnosed with COVID-19
6. Subject with any acute, chronic, or clinically significant disease as a result of physical examination or laboratory examination at the screening visit (Visit 1)
7. Subject with a history of malignancy within 5 years before the first dose of the investigational drug (except for basal cell and squamous cell carcinoma of the skin)
8. Subject with immune dysfunction including immunodeficiency disease through medical history and/or physical examination, or with a family history
9. Subject with a positive result of virus test (hepatitis B test, hepatitis A test, human immunodeficiency virus test, hepatitis C test) at the screening visit (Visit 1)
10. Subject who are significantly abnormal clinically in laboratory tests, electrocardiogram, chest, and X-rays performed at the screening visit (Visit 1) and those who are judged impossible to participate in the clinical trial at the discretion of the investigator
11. Subject with a history of hypersensitivity or severe allergic reaction to vaccine administration [e.g. anaphylaxis, Guillain-Barre syndrome, urticaria*, other clinically significant reactions requiring medical intervention]
12. Urticaria: Those with a history of systemic urticaria within 5 years before administration of investigational drugs
13. Subject with diseases on such systems as hepatobiliary, kidney, nervous system (central or peripheral), respiratory (asthma, pneumonia, etc.), endocrine (uncontrolled diabetes mellitus, hyperlipidemia, etc.), cardiovascular (congestive heart failure, coronary artery disease, myocardial infarction, uncontrolled hypertension) etc.), urinary, psychiatric, musculoskeletal disorders or have a clinically significant history that it is judged to be unable to participate in a clinical trial under the judgment of the investigator
14. Subject with autoimmune diseases including autoimmune hypothyroidism and psoriasis
15. Subject with suspected or history of alcohol or substance abuse 12 months prior to the scheduled screening visit (Visit 1). Alcohol abuse standards are defined as follows:
16. Subject who has had a serious adverse reaction to a drug containing the same component as the investigational drug or has a history of allergy
17. Subject who has had a cough, dyspnea, chills, muscle pain, headache, sore throat, loss of smell or taste and an acute fever in which the body temperature exceeds 37.5°C within 72 hours prior to administration of the clinical trial drug
18. Subject who has been diagnosed with COVID-19 and/or have been confirmed or treated for COVID-19 infection as a result of laboratory tests
19. Subject with a history of previous MERS-CoV or SARS-CoV infection
20. Subject with a history of hereditary or idiopathic angioneurotic edema

21. Subject with a history of organ or bone marrow transplantation

    [Relating to contraindicated drugs]

22. Subject who has experience in administering an immunosuppressant or immune modifying drug within 6 months prior to administration of an investigational drug
23. Patients with hemophilia who are at risk of serious bleeding when injected intramuscularly or are taking anticoagulants.
24. Subject who has received immunoglobulin or blood-derived products within 3 months prior to administration of the investigational drug or are expected to administer it during the clinical trial period
25. Subject who participated in other clinical trials similar to the investigational drug before the screening visit (Visit 1)
26. Subject with a history of MERS-CoV or SARS-CoV vaccination
27. Subject who haa received or plan to administer the vaccine within 4 weeks before/after administration of this investigational drug
28. Subject with a history of platelet-related disease or hemorrhagic disease, a history of severe bleeding or bruising after intramuscular injection or venipuncture or a person taking anticoagulants
29. If there is a history of dependent administration of psychotropic drugs or narcotic analgesics within 6 months prior to administration of the investigational drug or in case of a mental illness or social condition in which it is difficult to comply with the clinical trial procedure according to the judgment of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Injection in the muscle at 0day , 28 day	Biological: QTP104 1ug; Intramuscular injections of 1 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (QTP104) on days 1 and 28
Experimental: Cohort 2; Injection in the muscle at 0day , 28 day	Biological: QTP104 5ug; Intramuscular injections of 5 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (QTP104) on days 1 and 28
Experimental: Cohort 3; Injection in the muscle at 0day , 28 day	Biological: QTP104 25ug; Intramuscular injections of 25 µg of novel Lipid-Inorganic Nanoparticle (LION) formulated replicating RNA-based vaccine (QTP104) on days 1 and 28

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events(Immediated AEs)	Incidence rate of immediate adverse events (Immediated AEs)	30 minutes after each administration
Adverse event(solicited local / systemic AEs)	Incidence rate of expected local and systemic adverse events (solicited local / systemic AEs)	7 days after each administration
Adverse event(unsolicited AEs)	Incidence rate of unexpected adverse events (unsolicited AEs)	28 days after each administration
Adverse event(SAEs / serious ADRs)	Incidence rate of serious adverse events and adverse drug reactions (SAEs / serious ADRs)	28 days after each administration
Adverse event(AESI)	Incidence rate of adverse events of special interest (AESI)	394 days from 0 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of QTP104 vaccine as measured by IgG ELISA	Geometric mean titer (GMT) of SARS-CoV-2 Spike (S) protein IgG measured by ELISA at multiple time points after QTP104 administration compared to baseline.	Day 0, 29, 57, 180, 394
Proportion of subjects for seroconversion of IgG antibodies titer of QTP104	Proportion of subjects with a ≥4-fold increase in IgG antibody titer to SARS-CoV-2 by ELISA at multiple time points after QTP104 administration compared to baseline.	Day 0, 29, 57, 180, 394
Immunogenicity of QTP104 vaccine as measured by neutralizing antibodies	Geometric mean titer of neutralizing antibody measured by FRNT using Wild-Type Virus at multiple time points after QTP104 administration compared to baseline	Day 0, 29, 57, 180, 394

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To analyze the ratio of Th1/Th2 by measuring Th1- and Th2-type cytokines through ICS assay	To analyze the ratio of Th1/Th2 by measuring Th1- and Th2-type cytokines through ICS assay at 4weeks after 1st administration of QTP104 and 4weeks, 5months and 12months after 2nd administration of QTP104	Day 0, 29, 57, 180, 394
To analyze the cellular immune responses including number of antigen-specific IFN-γ secreting T cells (IFN-γ ELISPOT Assay)	To analyze the cellular immune responses including number of antigen-specific IFN-γ secreting T cells (IFN-γ ELISPOT Assay) at 4weeks after 1st administration of QTP 104 and 4weeks, 5months and 12months after 2nd administration of QTP104	Day 0, 29, 57, 180, 394

Collaborators and Investigators

• Sponsor: Quratis Inc.
• Investigators: Study Director: Yu Hwa Choi, Quratis Inc.; Principal Investigator: Joon-Sup Yeom, MD/PhD, Infectious Disease, Severance Hospital, Yonsei University College of Medicine; Principal Investigator: Young Goo Song, MD/PhD, Infectious Diseases, Gangnam Severance Hospital, Yonsei University College of Medicine

Publications and helpful links

Helpful Links

• korea

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2021
• Primary Completion (Actual): June 13, 2022
• Study Completion (Estimated): August 30, 2023

Study Registration Dates

• First Submitted: May 1, 2023
• First Submitted That Met QC Criteria: May 24, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): May 25, 2023
• Last Update Submitted That Met QC Criteria: May 24, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: mRNA Vaccine; Replicon mRNA; Self-replicating mRNA
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: CT-QTP104-002

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.: Yes