Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

• ClinicalTrials.gov Identifier: NCT04276896
• Recruitment Status: Recruiting
• First Posted: February 19, 2020
• Last Update Posted: March 19, 2020
• Sponsor: Shenzhen Geno-Immune Medical Institute
• Collaborators: Shenzhen Third People's Hospital; Shenzhen Second People's Hospital
• Information provided by (Responsible Party): Shenzhen Geno-Immune Medical Institute

Tracking Information

• First Submitted Date: February 17, 2020
• First Posted Date: February 19, 2020
• Last Update Posted Date: March 19, 2020
• Estimated Study Start Date: March 24, 2020
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2020)

• Clinical improvement based on the 7-point scale [ 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).
• Lower Murray lung injury score [ 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2020)

• 28-day mortality [ Time Frame: Measured from Day 0 through Day 28 ]
  Number of deaths during study follow-up
• Duration of mechanical ventilation [ Time Frame: Measured from Day 0 through Day 28 ]
  Duration of mechanical ventilation use in days. Multiple mechanical ventilation durations are summed up.
• Duration of hospitalization [ Time Frame: Measured from Day 0 through Day 28 ]
  Days that a participant spent at the hospital. Multiple hospitalizations are summed up.
• Proportion of patients with negative RT-PCR results [ Time Frame: 7 and 14 days after randomization ]
  Proportion of patients with negative RT-PCR results of virus in upper and/or lower respiratory tract samples.
• 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).
• 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.
• Frequency of vaccine/CTL Events [ Time Frame: Measured from Day 0 through Day 28 ]
  Frequency of vaccine/CTL Events
• Frequency of Serious vaccine/CTL Events [ Time Frame: Measured from Day 0 through Day 28 ]
  Frequency of Serious vaccine/CTL Events

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Pathogen Infection Covid-19 Infection

Intervention

Biological: 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.

Study Arms

Experimental: 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.

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 17, 2020): 100
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: July 31, 2023 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04276896
• Other Study ID Numbers: GIMI-IRB-20001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shenzhen Geno-Immune Medical Institute
• Original Responsible Party: Same as current
• Current Study Sponsor: Shenzhen Geno-Immune Medical Institute
• Original Study Sponsor: Same as current

Collaborators

• Shenzhen Third People's Hospital
• Shenzhen Second People's Hospital

Investigators

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

• PRS Account: Shenzhen Geno-Immune Medical Institute
• Verification Date: March 2020