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

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

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19, SARS-CoV-2

Intervention / Treatment
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* Biological: QTP104 1ug
* Biological: QTP104 5ug
* Biological: QTP104 25ug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female aged 19 to 55 years at the screening visit (Visit 1) Subject with a Body Mass Index (BMI) of 18kg/m2 or more and 30kg/m2 or less at the screening visit (Visit 1) 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) 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 Subject who can collect blood and urine during this clinical trial period including the last visit 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 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] 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) Subject who has a history of malignant tumors within the past 5 years Subject who has an immune dysfunction, including immunodeficiency disease, or a family history thereof through a medical history and/or physical examination Subject who has positive SARS-CoV-2 IgG Ab results during screening visit (Visit 1) Subject previously diagnosed with COVID-19 Subject with any acute, chronic, or clinically significant disease as a result of physical examination or laboratory examination at the screening visit (Visit 1) 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) Subject with immune dysfunction including immunodeficiency disease through medical history and/or physical examination, or with a family history 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) 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 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] Urticaria: Those with a history of systemic urticaria within 5 years before administration of investigational drugs 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 Subject with autoimmune diseases including autoimmune hypothyroidism and psoriasis 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: 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 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 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 Subject with a history of previous MERS-CoV or SARS-CoV infection Subject with a history of hereditary or idiopathic angioneurotic edema Subject with a history of organ or bone marrow transplantation [Relating to contraindicated drugs] Subject who has experience in administering an immunosuppressant or immune modifying drug within 6 months prior to administration of an investigational drug Patients with hemophilia who are at risk of serious bleeding when injected intramuscularly or are taking anticoagulants. 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 Subject who participated in other clinical trials similar to the investigational drug before the screening visit (Visit 1) Subject with a history of MERS-CoV or SARS-CoV vaccination Subject who haa received or plan to administer the vaccine within 4 weeks before/after administration of this investigational drug 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 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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA Vaccine, Replicon mRNA, Self-replicating mRNA