Safety and Immunity of Covid-19 aAPC Vaccine

• ClinicalTrials.gov Identifier: NCT04299724
• Recruitment Status: Recruiting
• First Posted: March 9, 2020
• Last Update Posted: March 9, 2020
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: Shenzhen Third People's Hospital; Shenzhen Second People's Hospital
• Information provided by (Responsible Party): Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Treat and Prevent Covid-19 Infection	Biological: Pathogen-specific aAPC	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Immunity Evaluation of A Covid-19 Coronavirus Artificial Antigen Presenting Cell Vaccine
• Actual Study Start Date: February 15, 2020
• Estimated Primary Completion Date: July 31, 2023
• Estimated Study Completion Date: December 31, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Injection of Covid-19/aAPC vaccine	Biological: Pathogen-specific aAPC; The subjects will receive three injections of 5x10^6 each Covid-19/aAPC vaccine via subcutaneous injections.

Outcome Measures

Primary Outcome Measures :

1. Frequency of vaccine events [ Time Frame: Measured from Day 0 through Day 28 ]
   Frequency of vaccine events such as fever, rash, and abnormal heart function.
2. Frequency of serious vaccine events [ Time Frame: Measured from Day 0 through Day 28 ]
   Frequency of serious vaccine events
3. Proportion of subjects with positive T cell response [ Time Frame: 14 and 28 days after randomization ]

Secondary Outcome Measures :

1. 28-day mortality [ Time Frame: Measured from Day 0 through Day 28 ]
   Number of deaths during study follow-up
2. Duration of mechanical ventilation if applicable [ Time Frame: Measured from Day 0 through Day 28 ]
   Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up
3. Proportion of patients in each category of the 7-point scale [ Time Frame: 7,14 and 28 days after randomization ]
   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)
4. Proportion of patients with normalized inflammation factors [ Time Frame: 7 and 14 days after randomization ]
   Proportion of patients with different inflammation factors in normalization range
5. Clinical improvement based on the 7-point scale if applicable [ Time Frame: 28 days after randomization ]
   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)
6. Lower Murray lung injury score if applicable [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 80 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Lung-Ji Chang; +86(755)8672 5195; c@szgimi.org

Locations

China, Guangdong

Shenzhen Geno-immune Medical Institute; Recruiting

Shenzhen, Guangdong, China, 518000

Contact: Lung-Ji Chang 86-755-86725195 c@szgimi.org

Sponsors and Collaborators

Shenzhen Geno-Immune Medical Institute

Shenzhen Third People's Hospital

Shenzhen Second People's Hospital

Investigators

• Principal Investigator: Lung-Ji Chang; Shenzhen Geno-Immune Medical Institute

More Information

• Responsible Party: Lung-Ji Chang, President, Shenzhen Geno-Immune Medical Institute
• ClinicalTrials.gov Identifier: NCT04299724
• Other Study ID Numbers: GIMI-IRB-20002
• First Posted: March 9, 2020
• Last Update Posted: March 9, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Lung-Ji Chang, Shenzhen Geno-Immune Medical Institute:

Lentiviral vector, Covid-19/aAPC vaccine

Additional relevant MeSH terms:

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases