Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Immunity and Safety of Covid-19 Synthetic Minigene Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04276896
Recruitment Status : Recruiting
First Posted : February 19, 2020
Last Update Posted : March 19, 2020
Sponsor:
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  ICMJE February 17, 2020
First Posted Date  ICMJE February 19, 2020
Last Update Posted Date March 19, 2020
Estimated Study Start Date  ICMJE March 24, 2020
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Immunity and Safety of Covid-19 Synthetic Minigene Vaccine
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Pathogen Infection Covid-19 Infection
Intervention  ICMJE 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  ICMJE 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

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 17, 2020)
100
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2024
Estimated Primary Completion Date July 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 80 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lung-Ji Chang, PhD +86(755)8672 5195 c@szgimi.org
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04276896
Other Study ID Numbers  ICMJE 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  ICMJE
Plan to Share IPD: No
Responsible Party Shenzhen Geno-Immune Medical Institute
Study Sponsor  ICMJE Shenzhen Geno-Immune Medical Institute
Collaborators  ICMJE
  • Shenzhen Third People's Hospital
  • Shenzhen Second People's Hospital
Investigators  ICMJE
Principal Investigator: Lung-Ji Chang, PhD Shenzhen Geno-Immune Medical Institute
PRS Account Shenzhen Geno-Immune Medical Institute
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP