Immuniteit en veiligheid van covid-19 synthetisch minigene vaccin
Fase I/II Multicenter-onderzoek naar lentiviraal minigene vaccin (LV-SMENP) van Covid-19 Coronavirus
In December 2019, viral pneumonia caused by a novel beta-coronavirus (Covid-19) broke out in Wuhan, China. Some patients rapidly progressed and suffered severe acute respiratory failure and died, making it imperative to develop a safe and effective vaccine to treat and prevent severe Covid-19 pneumonia. Based on detailed analysis of the viral genome and search for potential immunogenic targets, a synthetic minigene has been engineered based on conserved domains of the viral structural proteins and a polyprotein protease. The infection of Covid-19 is mediated through binding of the Spike protein to the ACEII receptor, and the viral replication depends on molecular mechanisms of all of these viral proteins. This trial proposes to develop and test innovative Covid-19 minigenes engineered based on multiple viral genes, using an efficient lentiviral vector system (NHP/TYF) to express viral proteins and immune modulatory genes to modify dendritic cells (DCs) and to activate T cells. In this study, the safety and efficacy of this LV vaccine (LV-SMENP) will be investigated.
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
Background: The 2019 discovered new coronavirus, Covid-19, is an enveloped positive strand single strand RNA virus. The number of Covid-19 infected people has increased rapidly and WHO has warned that the spread of Covid-19 may soon become pandemic and have disastrous outcomes. Covid-19 could pose a serious threat to human health and global economy. There is no vaccine available or clinically approved antiviral therapy as yet. This study aims to evaluate the safety and efficacy of treating Covid-19 infections with a novel lentiviral based DC and T cell vaccines.
Objective: Primary study objectives: Injection and infusion of LV-SMENP DC and antigen-specific cytotoxic T cell vaccines to healthy volunteers and Covid-19 infected patients to evaluate the safety.
Secondary study objectives: To evaluate the anti- Covid-19 efficacy of the LV-SMENP DC and antigen-specific cytotoxic T cell vaccines.
Design:
- Based on the genomic sequence of the new coronavirus Covid-19, select conserved and critical structural and protease protein domains to engineer lentiviral SMENP minigenes to express Covid-19 antigens.
- LV-SMENP-DC vaccine is made by modifying DC with lentivirus vectors expressing Covid-19 minigene SMENP and immune modulatory genes. CTLs will be activated by LV-DC presenting Covid-19 specific antigens.
- LV-DC vaccine and antigen-specific CTLs are prepared in 7~21 days. Subject will receive total 5x10^6 cells of LV-DC vaccine and 1x10^8 antigen-specific CTLs via sub-cutaneous injection and IV infusion, respectively. Patients are followed weekly for one month after the infusion, monthly for 3 months, and then every 3 months until the trial ends.
Studietype
Inschrijving (Werkelijk)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studie Locaties
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Guangdong
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Shenzhen, Guangdong, China, 518000
- Shenzhen Geno-immune Medical Institute
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
Inclusion Criteria:
- Laboratory (RT-PCR) confirmed Covid-19 infection in throat swab and/or sputum and/or lower respiratory tract samples;
- The interval between the onset of symptoms and randomized is within 7 days. The onset of symptoms is mainly based on fever. If there is no fever, cough or other related symptoms can be used;
- White blood cells ≥ 3,500 / μl, lymphocytes ≥ 750 / μl;
- Human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or tuberculosis (TB) test is negative;
- Sign the Informed Consent Form on a voluntary basis;
Exclusion Criteria:
- Subject infected with HCV (HCV antibody positive), HBV (HBsAg positive), HIV (HIV antibody positive), or HTLV (HTLV antibody positive).
- Subject is albumin-intolerant.
- Subject with life expectancy less than 4 weeks.
- Subject participated in other investigational somatic cell therapies within past 30 days.
- Subject with positive pregnancy test result.
- Researchers consider unsuitable.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: NVT
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
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Experimenteel: pathogen-specific DC and CTLs
Patients will receive approximately 5x10^6 LV-DC vaccine and 1x10^8 CTLs via sub-cutaneous injections and iv infusions, respectively. |
Patients will receive approximately 5x10^6 LV-DC vaccine and 1x10^8 CTLs via sub-cutaneous injections and iv infusions, respectively. |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Clinical improvement based on the 7-point scale
Tijdsspanne: 28 days after randomization
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A decline of 2 points on the 7-point scale from admission means better outcome. The 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death). |
28 days after randomization
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Lower Murray lung injury score
Tijdsspanne: 7 days after randomization
|
Murray lung injury score decrease more than one point means better outcome. The Murray scoring system range from 0 to 4 according to the severity of the condition. |
7 days after randomization
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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28-day mortality
Tijdsspanne: Measured from Day 0 through Day 28
|
Number of deaths during study follow-up |
Measured from Day 0 through Day 28
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Duration of mechanical ventilation
Tijdsspanne: Measured from Day 0 through Day 28
|
Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up. |
Measured from Day 0 through Day 28
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Duration of hospitalization
Tijdsspanne: Measured from Day 0 through Day 28
|
Days that a participant spent at the hospital. Multiple hospitalizations are summed up. |
Measured from Day 0 through Day 28
|
|
Proportion of patients with negative RT-PCR results
Tijdsspanne: 7 and 14 days after randomization
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Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples. |
7 and 14 days after randomization
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Proportion of patients in each category of the 7-point scale
Tijdsspanne: 7,14 and 28 days after randomization
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Proportion of patients in each category of the 7-point scale, the 7-category ordinal scale that ranges from 1 (discharged with normal activity) to 7 (death). |
7,14 and 28 days after randomization
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Proportion of patients with normalized inflammation factors
Tijdsspanne: 7 and 14 days after randomization
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Proportion of patients with different inflammation factors in normalization range. |
7 and 14 days after randomization
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Frequency of vaccine/CTL Events
Tijdsspanne: Measured from Day 0 through Day 28
|
Frequency of vaccine/CTL Events |
Measured from Day 0 through Day 28
|
|
Frequency of Serious vaccine/CTL Events
Tijdsspanne: Measured from Day 0 through Day 28
|
Frequency of Serious vaccine/CTL Events |
Measured from Day 0 through Day 28
|
Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: Lung-Ji Chang, PhD, Shenzhen Geno-Immune Medical Institute
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Werkelijk)
Studie voltooiing (Werkelijk)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- GIMI-IRB-20001
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
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