Clinical trial NCT04299724: Safety and Immunity of Covid-19 aAPC Vaccine
Official title: Safety and Immunity Evaluation of A Covid-19 Coronavirus Artificial Antigen Presenting Cell Vaccine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Treat and Prevent Covid-19 Infection
Keywords: Lentiviral vector, Covid-19/aAPC vaccine
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: 2020-03-09
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 (Covid-19) caused by a novel beta-coronavirus (SARS-CoV-2) 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 universal vaccine 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 artificial antigen presenting cells (aAPC) and to activate T cells. In this study, the safety and immune reactivity of this aAPC vaccine will be investigated.

Detailed description: Background:

The 2019 discovered new coronavirus, SARS-CoV-2, is an enveloped positive strand single strand RNA virus. The number of SARS-CoV-2 infected people has increased rapidly and WHO has warned that the pandemic spread of Covid-19 is imminent and would have disastrous outcomes. Covid-19 could pose a serious threat to human health and the global economy. There is no vaccine available or clinically approved antiviral therapy as yet. This study aims to evaluate the safety and immune reactivity of a genetically modified aAPC universal vaccine to treat and prevent Covid-19.

Objective:

Primary study objectives: Injection of Covid-19/aAPC vaccine to volunteers to evaluate the safety.

Secondary study objectives: To evaluate the anti- Covid-19 reactivity of the Covid-19/aAPC vaccine.

Design:

1. Based on the genomic sequence of the new coronavirus SARS-CoV-2, select conserved and critical structural and protease protein domains to engineer lentiviral minigenes to express SARS-CoV-2 antigens.
2. The Covid-19/aAPC vaccine is prepared by applying lentivirus modification including immune modulatory genes and the viral minigenes, to the artificial antigen presenting cells (aAPCs). The Covid-19/aAPCs are then inactivated for proliferation and extensively safety tested.
3. The subjects receive a total of 5x10\^ 6 cells each time by subcutaneous injection at 0, 14 and 28 days. The subjects are followed-up with peripheral blood tests at 0, 14, 21, 28 and 60 days until the end of the test.

Eligibility criteria: Inclusion Criteria:

* Healthy and Covid-19-positive volunteers
* The interval between the onset of symptoms and randomized is within 7 days in Covid-19 patients. 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 negative;
* Sign the Informed Consent voluntarily;

Exclusion Criteria:

* Subject with active HCV, HBV or HIV infection.
* Subject is albumin-intolerant.
* Subject with life expectancy less than 4 weeks.
* Subject participated in other investigational vaccine therapies within the past 60 days.
* Subject with positive pregnancy test result.
* Researchers consider unsuitable.

Primary outcomes:
measure: Frequency of vaccine events
timeFrame: Measured from Day 0 through Day 28
measure: Frequency of serious vaccine events
timeFrame: Measured from Day 0 through Day 28
measure: Proportion of subjects with positive T cell response
timeFrame: 14 and 28 days after randomization
Secondary outcomes:
measure: 28-day mortality
timeFrame: Measured from Day 0 through Day 28
measure: Duration of mechanical ventilation if applicable
timeFrame: Measured from Day 0 through Day 28
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: Clinical improvement based on the 7-point scale if applicable
timeFrame: 28 days after randomization
measure: Lower Murray lung injury score if applicable
timeFrame: 7 days after randomization
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Shenzhen Geno-immune Medical Institute
state: Guangdong
Study officials:
affiliation: Shenzhen Geno-Immune Medical Institute
name: Lung-Ji Chang
role: PRINCIPAL_INVESTIGATOR
References: