Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

NCT ID: NCT04276896

Last Updated: 2020-03-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-24
• Study Completion Date: 2024-12-31

Brief Summary

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.

Detailed Description

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:

1. 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.

2. 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.

3. 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.

Conditions

Pathogen Infection Covid-19 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs

Intervention Type: BIOLOGICAL

Patients will receive approximately 5x10\^6 LV-DC vaccine and 1x10\^8 CTLs via sub-cutaneous injections and iv infusions, respectively.

Interventions

Injection and infusion of LV-SMENP-DC vaccine and antigen-specific CTLs

Patients will receive approximately 5x10\^6 LV-DC vaccine and 1x10\^8 CTLs via sub-cutaneous injections and iv infusions, respectively.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Third People's Hospital

OTHER

Sponsor Role: collaborator

Shenzhen Second People's Hospital

OTHER

Sponsor Role: collaborator

Shenzhen Geno-Immune Medical Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lung-Ji Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

Shenzhen Geno-Immune Medical Institute

Locations

Shenzhen Geno-immune Medical Institute

Shenzhen, Guangdong, China

Site Status: RECRUITING

Shenzhen Second People's Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

Shenzhen Third People's Hospital

Shenzhen, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Lung-Ji Chang, PhD

Role: CONTACT

c@szgimi.org

+86(755)8672 5195

Facility Contacts

Lung-Ji Chang, PhD

Role: primary

c@szgimi.org

86-755-86725195

Other Identifiers

GIMI-IRB-20001

Identifier Type: -

Identifier Source: org_study_id