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

NCT04934111 | Unknown Phase 1

• 1 other identifier: COVAC Uganda
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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.

Conditions

COVID-19

Keywords

SARS-CoV-2, LNP-nCOV saRNA-02, COVID-19

Outcome Measures

Primary Outcomes (7)

• Number of participants with solicited local injection site reactions

  Number of participants with solicited local injection site reactions starting within 7 days of administration of the vaccine: pain, tenderness, erythema, swelling

  7 days after each injection

• Number of participants with solicited systemic reactions starting within 7 days of administration of the vaccine

  Number of participants with solicited systemic reactions starting within 7 days of administration of the vaccine: pyrexia, fatigue, myalgia, headache, chills, arthralgia

  7 days after each injection

• Number of participants with unsolicited adverse reactions (ARs) throughout the study

  Number of participants with unsolicited adverse reactions (ARs) throughout the study period (including serious ARs)

  6 months

• Number of participants with serious Adverse Events

  Number of participants with serious Adverse Events

  6 months

• Number of participants with unsolicited adverse events

  Number of participants with unsolicited adverse events throughout the study period

  6 months

• The titer of serum neutralizing antibodies 2 weeks after the second vaccination in the SARS-CoV-2 pseudovirus-based neutralization assay

  The titer of serum neutralizing antibodies 2 weeks after the second vaccination in the SARS-CoV-2 pseudovirus-based neutralization assay

  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

  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

  from day 1, through six months

Secondary Outcomes (5)

• Cell-mediated vaccine-induced immune responses measured by T- and B- cell ELISpot in study participants

  from day 1, through six months

• Cell-mediated vaccine-induced immune responses measured by flow cytometry and intracellular cytokine staining in study participants

  from day 1, through six months

• The profile of class and sub-class of antibody response

  from day 1, through six months

• Laboratory markers of infection and infection-induced immunity

  through the 6 months of the trial

• Incidence of thrombocytopenia of any grade confirmed on repeat testing if possible

  Through 6 months of the trial

Study Arms (1)

LNP-nCOV saRNA-02 Vaccine arm

EXPERIMENTAL

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

Interventions

LNP-nCOV saRNA-02 Vaccine DRUG

a self-amplifying ribonucleic acid (saRNA) vaccine encoding the S glycoprotein of SARS-CoV-2, the causative agent of COVID-19

LNP-nCOV saRNA-02 Vaccine arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Pregnant or lactating
• 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.
• History of anaphylaxis or angioedema
• Active SARS-CoV-2 infection at enrolment, based on DNA-PCR testing
• Discordant RDT result
• History of severe or multiple allergies to drugs or pharmaceutical agents
• History of severe local or general reaction to vaccination defined as:
• local: extensive, indurated redness and swelling involving most of the arm, not resolving within 72 hours
• general: fever ≥39.5 °C within 48 hours; bronchospasm; laryngeal edema; collapse; convulsions or encephalopathy within 72 hours
• Ever received an experimental vaccine against COVID-19
• Receipt of any immunosuppressive agents within 18 weeks of screening by any route other than topical
• Detection of antibodies to hepatitis C
• Detection of antibodies to HIV
• 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
• Participating in another clinical trial with an investigational drug or device, or treated with an investigational drug within 28 days of screening.

Sponsors & Collaborators

• MRC/UVRI and LSHTM Uganda Research Unit: lead

Study Sites (1)

MRC/UVRI & LSHTM Uganda Research Unit

Entebbe, P.O.Box 49 Entebbe, Uganda

RECRUITING

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MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

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

Study Officials

• Pontiano Kaleebu, PhD

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jonathan Kitonsa, MBchB, MPH

CONTACT

+256774305403; Jonathan.Kitonsa@mrcuganda.org

Benjamin Pierce, PhD

CONTACT

020 7594 6663; b.pierce@imperial.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 10, 2021
• First Posted: June 22, 2021
• Study Start: December 2, 2021
• Primary Completion: November 1, 2022
• Study Completion: December 31, 2022
• Last Updated: April 22, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, 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

Locations

UG (1)