Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Immunogenicity of LNP-nCOV saRNA-02 Vaccine Against SARS-CoV-2, the Causative Agent of COVID-19 (COVAC-Uganda)

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: NCT04934111
Recruitment Status : Not yet recruiting
First Posted : June 22, 2021
Last Update Posted : June 22, 2021
Sponsor:
Information provided by (Responsible Party):
MRC/UVRI and LSHTM Uganda Research Unit

Brief Summary:
COVAC Uganda is a study that is looking at the use of an innovative self-amplifying RNA (saRNA) vaccine (LNP-nCOV saRNA-02) against the virus (SARS-CoV-2) that causes COVID-19 and assessing the immune response in SARS-CoV-2 antibody seronegative and seropositive individuals. saRNA is designed to amplify the quantity of RNA upon injection to produce further antigen, thereby enabling lower doses for administration. In the trial "COVAC1", Imperial College London is currently evaluating one COVID-19 saRNA vaccine candidate in doses from 0.1-10ug for individuals who are seronegative for SARS-CoV-2 antibodies at baseline. Interim analyses of COVAC1 has shown a dose dependent response; however, up to 50% of seronegative participants receiving doses of 2.5-10ug do not seroconvert. The investigators hypothesize that a lack of seroconversion is due to type I and III interferon (IFN) production, which can inhibit translation and degrade cellular mRNA. Another variable that can enhance antibody production is serological history: recent studies have shown that seropositive individuals respond significantly better than naïve individuals who received the Pfizer or Moderna RNA-based COVID-19 vaccine. Therefore, designing the saRNA backbone to dampen IFN production and evaluating this in individuals seropositive at baseline will inform the optimised use of this innovative technology. In COVAC Uganda, the investigators aim to test an saRNA vaccine modified to dampen the activation of type I and III IFN, to increase antibody production, for individuals who are seronegative and seropositive for SARS-CoV-2 antibodies at baseline, to evaluate whether people with pre-existing seropositivity have enhanced immune responses compared to those without. This trial is NOT looking at whether or not the vaccine is effective in terms of protection. It is just assessing whether and how well the immune system responds based on SARS-CoV-2 antibodies at baseline and its safety.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: LNP-nCOV saRNA-02 Vaccine Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This phase I clinical study builds on clinical experience using the LNP nCoV saRNA vaccine currently under evaluation in COVAC1 (Being conducted in the UK). The trial will be conducted in 18-45 year olds in a single centre supervised by the Chief Investigator, by allocating the 42 participants into two groups, based on seroconversion status. These will include 21 SARS-CoV-2 seronegative and 21 SARs-CoV-2 seropositive individuals. Participants in each group will be given a dose of 5.0ug at 0 weeks and 4 weeks.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Clinical Trial to Assess the Safety and Immunogenicity of LNP-nCOV saRNA-02, a Self-amplifying Ribonucleic Acid (saRNA) Vaccine, in SARS-CoV-2 Seronegative and Seropositive Uganda Population
Estimated Study Start Date : September 2021
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : August 2022

Arm Intervention/treatment
Experimental: LNP-nCOV saRNA-02 Vaccine arm
Participants that have evidence of previous infection with SARS-CoV-2 and those with no evidence of previous infection will all receive receive LNP-nCOV saRNA-02 Vaccine. Both groups will be given a dose of 5.0ug at 0 weeks and 4 weeks.
Drug: LNP-nCOV saRNA-02 Vaccine
a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative agent of COVID-19




Primary Outcome Measures :
  1. Number of participants with solicited local injection site reactions [ Time Frame: 7 days after each injection ]
    Number of participants with solicited local injection site reactions starting within 7 days of administration of the vaccine: pain, tenderness, erythema, swelling

  2. Number of participants with solicited systemic reactions starting within 7 days of administration of the vaccine [ Time Frame: 7 days after each injection ]
    Number of participants with solicited systemic reactions starting within 7 days of administration of the vaccine: pyrexia, fatigue, myalgia, headache, chills, arthralgia

  3. Number of participants with unsolicited adverse reactions (ARs) throughout the study [ Time Frame: 6 months ]
    Number of participants with unsolicited adverse reactions (ARs) throughout the study period (including serious ARs)

  4. Number of participants with serious Adverse Events [ Time Frame: 6 months ]
    Number of participants with serious Adverse Events

  5. Number of participants with unsolicited adverse events [ Time Frame: 6 months ]
    Number of participants with unsolicited adverse events throughout the study period

  6. The titer of serum neutralizing antibodies 2 weeks after the second vaccination in the SARS-CoV-2 pseudovirus-based neutralization assay [ Time Frame: from day 1, through six months ]
    The titer of serum neutralizing antibodies 2 weeks after the second vaccination in the SARS-CoV-2 pseudovirus-based neutralization assay

  7. The titer of vaccine-induced serum IgG binding antibody responses to the SARS-CoV-2 S glycoprotein 2 weeks after the first and second vaccinations [ Time Frame: from day 1, through six months ]
    The titer of vaccine-induced serum IgG binding antibody responses to the SARS-CoV-2 S glycoprotein 2 weeks after the first and second vaccinations


Secondary Outcome Measures :
  1. Cell-mediated vaccine-induced immune responses measured by T- and B- cell ELISpot in study participants [ Time Frame: from day 1, through six months ]
    Cell-mediated vaccine-induced immune responses measured by T- and B- cell ELISpot in study participants

  2. Cell-mediated vaccine-induced immune responses measured by flow cytometry and intracellular cytokine staining in study participants [ Time Frame: from day 1, through six months ]
    Cell-mediated vaccine-induced immune responses measured by flow cytometry and intracellular cytokine staining in study participants

  3. The profile of class and sub-class of antibody response [ Time Frame: from day 1, through six months ]
    The profile of class and sub-class of antibody response

  4. Laboratory markers of infection and infection-induced immunity [ Time Frame: through the 6 months of the trial ]
    Laboratory markers of infection and infection-induced immunity

  5. Incidence of thrombocytopenia of any grade confirmed on repeat testing if possible [ Time Frame: Through 6 months of the trial ]
    Incidence of thrombocytopenia of any grade confirmed on repeat testing if possible



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy adults from the following aged 18-45 years on the day of screening
  2. At similar risk of acquiring SARS-CoV-2 infection to the general population
  3. Willing and able to provide informed consent
  4. If female and of childbearing potential, willing to use a highly effective method of contraception from screening until 18 weeks after last injection
  5. If male and not sterilised, willing to avoid impregnating female partners from screening until 18 weeks after last injection
  6. Willing to avoid all other vaccines from within 4 weeks before the first injection through to 22 weeks after the second injection
  7. Willing and able to comply with visit schedule, complete vaccine diaries and provide samples
  8. Willing to grant authorised persons access to his/her trial-related medical record and GP records either directly or indirectly

Exclusion Criteria:

  1. Pregnant or lactating
  2. Has a significant clinical history, physical finding on clinical examination during screening, or presence of a disease that is active or requires treatment to control it, including cardiac, respiratory, endocrine, metabolic, autoimmune, liver, neurological, oncological, psychiatric, immunosuppressive/immunodeficient or other disorders which in the opinion of the investigator is not compatible with healthy status, increases the risk of severe COVID-19, may compromise the volunteer's safety, preclude vaccination or compromise interpretation of the immune response to vaccine. Individuals with mild/moderate, well-controlled comorbidities are allowed.
  3. History of anaphylaxis or angioedema
  4. Active SARS-CoV-2 infection at enrolment, based on DNA-PCR testing
  5. Discordant RDT result
  6. History of severe or multiple allergies to drugs or pharmaceutical agents
  7. History of severe local or general reaction to vaccination defined as:

    1. local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
    2. general: fever ≥39.5 °C within 48 hours; bronchospasm; laryngeal edema; collapse; convulsions or encephalopathy within 72 hours
  8. Ever received an experimental vaccine against COVID-19
  9. Receipt of any immunosuppressive agents within 18 weeks of screening by any route other than topical
  10. Detection of antibodies to hepatitis C
  11. Detection of antibodies to HIV
  12. Grade 1 and above abnormalities in routine laboratory parameters using the FDA toxicity table Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. https://www.fda.gov/media/73679/download
  13. Participating in another clinical trial with an investigational drug or device, or treated with an investigational drug within 28 days of screening.
  14. Has received an immunisation within 28 days of screening
  15. Has received an authorised COVID-19 vaccine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04934111


Contacts
Layout table for location contacts
Contact: Jonathan Kitonsa, MBchB, MPH +256774305403 Jonathan.Kitonsa@mrcuganda.org
Contact: Benjamin Pierce 020 7594 6663 b.pierce@imperial.ac.uk

Locations
Layout table for location information
Uganda
MRC/UVRI & LSHTM Uganda Research Unit
Entebbe, Uganda, P.O.Box 49 Entebbe
Contact: Jonathan Kitonsa, MBchB, MPH    +256774305403    Jonathan.Kitonsa@mrcuganda.org   
Sponsors and Collaborators
MRC/UVRI and LSHTM Uganda Research Unit
Investigators
Layout table for investigator information
Principal Investigator: Pontiano Kaleebu, PhD MRC/UVRI & LSHTM Uganda Research Unit
Publications:
NCT04283461. Safety and Immunogenicity Study of 2019-nCoV Vaccine (mRNA-1273) to Prevent SARS-CoV-2 Infection

Layout table for additonal information
Responsible Party: MRC/UVRI and LSHTM Uganda Research Unit
ClinicalTrials.gov Identifier: NCT04934111    
Other Study ID Numbers: COVAC Uganda
First Posted: June 22, 2021    Key Record Dates
Last Update Posted: June 22, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data will be shared according to the Imperial College London data sharing policies, adherent to General Data Protection Regulations (https://www.imperial.ac.uk/research-and-innovation/research-office/research-governance-and-integrity/what-is-research-governance-and-integrity/data-protection---information-for-participants/) and the MRC/UVRI & LSHTM Uganda Research Unit Data Sharing Policy (https://www.mrcuganda.org/publications/data-sharing-policy) and controlled access approach.
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Data will be available for sharing after study completion. Data may be assumed to be indefinitely available after that point until otherwise stated.
Access Criteria: Criteria may be accessed through link below
URL: https://www.imperial.ac.uk/research-and-innovation/research-office/research-governance-and-integrity/what-is-research-governance/data-protection---information-for-participants/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by MRC/UVRI and LSHTM Uganda Research Unit:
SARS-CoV-2, LNP-nCOV saRNA-02, COVID-19
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases