Clinical trial NCT04276896: Immunity and Safety of Covid-19 Synthetic Minigene Vaccine
Official title: Phase I/II Multicenter Trial of Lentiviral Minigene Vaccine (LV-SMENP) of Covid-19 Coronavirus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Pathogen Infection Covid-19 Infection
Keywords: Lentiviral vector
LV-DC vaccine
Covid-19 CTL
Lead sponsor: Shenzhen Geno-Immune Medical Institute
Sponsor class: OTHER
Collaborators: name: Shenzhen Third People's Hospital
name: Shenzhen Second People's Hospital
First posted: 2020-02-19
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical improvement based on the 7-point scale
timeFrame: 28 days after randomization
measure: Lower Murray lung injury score
timeFrame: 7 days after randomization
Secondary outcomes:
measure: 28-day mortality
timeFrame: Measured from Day 0 through Day 28
measure: Duration of mechanical ventilation
timeFrame: Measured from Day 0 through Day 28
measure: Duration of hospitalization
timeFrame: Measured from Day 0 through Day 28
measure: Proportion of patients with negative RT-PCR results
timeFrame: 7 and 14 days after randomization
measure: Proportion of patients in each category of the 7-point scale
timeFrame: 7,14 and 28 days after randomization
measure: Proportion of patients with normalized inflammation factors
timeFrame: 7 and 14 days after randomization
measure: Frequency of vaccine/CTL Events
timeFrame: Measured from Day 0 through Day 28
measure: Frequency of Serious vaccine/CTL Events
timeFrame: Measured from Day 0 through Day 28
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Third People's Hospital
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References: