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

• Status: Not yet recruiting
• Trial end date: 2022-08-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: MRC/UVRI and LSHTM Uganda Research Unit

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