FIH Study to Evaluate the Safety and Efficacy of COVI-VAC vaccine [COVID-19]
Research type
Research Study
Full title
First-in-human, Randomised, Double-blind, Placebo-controlled, Dose-escalation Study in Health Young Adults Evaluating the Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Candidate for Prevention of COVID-19.
IRAS ID
288852
Contact name
Daryl Bendel
Contact email
Sponsor organisation
Codagenix, Inc.
Eudract number
2020-004164-25
Duration of Study in the UK
1 years, 5 months, 2 days
Research summary
Research Results
This is a First-in-human, Randomised, Double-Blind Placebo-controlled, Dose-escalation Study Evaluating the Safety and Immunogenicity of COVI-VAC in Healthy Young Adults aged 18-30 years inclusive.Vaccines are the most cost-effective way of controlling pandemic outbreaks and the international community have stepped-up their efforts towards developing one against COVID-19. A safe and effective vaccine to prevent COVID-19 is an urgent worldwide medical need. Although many vaccines are in development, none are currently licensed for COVID-19.
COVI-VAC is an intranasal, live, attenuated (weakend) vaccine COVID-19 vaccine that is being developed by Codagenix who are funding this study. The vaccine contains the SARS-CoV-2 virus that has been weakened. Attenuated vaccines tend to give good immune responses and some of the best vaccines we have (such as MMR, nasal flu vaccines, and shingles vaccines) are attenuated viruses.
COVI-VAC is the first attenuated vaccine to be studied for COVID-19 and will be given by nose drops. We do not yet know if one dose or two doses will be needed, so we plan to study both options in this study. We are also don’t yet know the best dose to give, so we plan to study three doses in a dose escalating way. We will carefully check the safety of lower doses before going to higher doses.
We plan to have about 48 healthy young participants in this study. Study participants will need to spend at least 14 days after treatment in our quarantine facility on one or possibly two occasions. Participants will have to follow strict restrictions and will be tested to make sure they can’t pass the vaccine on to other people in their home or community.
Summary of results
Study design:
Double-blind, randomised, and placebo-controlled dose escalation study. For dose escalation studies a lower dose of the vaccine will be given first, then if there are no safety concerns, a higher dose will be given to later participants. A plaque forming unit (PFU) is a way to measure the amount of live virus within a sample the higher the PFU the higher the concentration of virus within the sample.
48 healthy volunteers aged between 18 and 48 were randomised to receive either 1 or 2 doses of COVI-VAC vaccine of different dose levels or a placebo. For this study there were three dose levels. ‘Approximately’ as it is not possible to measure exactly;
- Dose Level 1: approximately 5x10^4 (50 000) PFU;
- Dose Level 2: approximately 5x10^5 (500 000) PFU;
- Dose Level 3: approximately 5x10^6 (5 000 000) PFU;Safety:
COVI-VAC appeared safe and well tolerated at all dose groups tested. No statistically significant difference between groups was seen in proportion of participants with any AEs. No dose effect or clinically meaningful differences between the vaccine groups and the placebo group were seen for the percentages of participants with TEAEs. There were no deaths, SAE, or AEs leading to study discontinuation.
Adverse Events (AEs): There was a total of 61 treatment emergent adverse events (TEAEs) which occurred after vaccine/placebo had been administered. Most TEAEs reported were mild. Four participants in the COVI-VAC dosing groups experienced 5 moderate AEs which were all deemed unrelated to the vaccine by the investigator:
- COVID-19 (Dose Level 1 – 2 doses);
- Back Pain (Dose Level 2 – 1 dose);
- Headache (Dose Level 1 – 2 doses);
- Abdominal distension (Swelling of the abdomen) and COVID-19 infection (Dose Level 3 – 2 doses);
5 AEs were deemed to be related to the treatment in 4 participants, all these AEs were mild in severity:
- Lacrimation (secretion of tears) increased in two participants; Placebo and Dose Level 2 – 1 dose group;
- Rhinalgia (pain in the nose); Dose Level 2 – 2 doses group;
- Ocular hyperaemia (increased blood flow to the eyes); Placebo Group;
- Alanine aminotransferase (Liver enzyme) increase; Placebo group; One participant from the placebo group reported a serious AE (SAE) of moderate testis cancer.Immunogenicity:
Serum antibody response increased with increasing dose and after the second COVI-VAC dose within each dose group. In the high-dose group, responder rates of 80 to 100% (depending on assay) were seen after 2 doses of COVI-VAC. Cellular immune response to parts of the virus shared across different variants also increased with increasing dose and after the second COVI-VAC dose within each dose group. Mucosal immune response (IgA against Spike RBD) was seen after 2 doses in 40 to 50% of participants but was not dose dependent. No impact of baseline immunity against seasonal human coronaviruses (a cause of common colds) was seen on immunogenicity of COVI-VAC, as measured by spike IgG titer.Viral Shedding:
Vaccine virus shedding in the respiratory tract was self-limited and generally below levels likely to result in transmission. Shedding was less after the second dose in the high dose group, suggesting protection against re-challenge. No virus was found in fecal samples from study participants.Genetic Stability:
Analysis of the vaccine virus remaining in the airway over time showed that the virus was stable and did not mutate.Preliminary Efficacy:
No participants reported events consistent with respiratory illness through to Day 57.Conclusion:
In conclusion, the benefit-risk profile shown in this study in young, healthy adults with very low risk from SARS-CoV-2 infection supports further evaluation of COVI-VAC in higher-risk populations, in children, and as a booster vaccine.CSR Addendum (data after Day 57 through the end of the study):
Most (87.5%) participants were vaccinated with a licensed COVID-19 vaccine after Day 57, so routine antibody testing was not interpretable. An antibody response to nucleocapsid protein (which does not happen after licensed COVID-19 vaccines) showed that many participants showed evidence of seroconverted of natural SARS-CoV-2 infection in the follow-up period. Rates were similar in the active vaccine and placebo groups.
Reporting of respiratory illnesses in the follow-up period was consistent with the antibody results, with 27 asymptomatic or symptomatic COVID-19 infections reported in 25 (52%) of participants. Incidence rates and reported symptoms were similar in all the groups. Five of the 27 COVID-19 infections were asymptomatic, and 20 were of mild severity. The 2 moderate cases were in a participant in the Dose Level 1 – 2 doses group and a participant in the Dose Level 3 – 2 doses group.
There was no change to overall conclusions of the study. Further assessment in other populations is ongoing.REC name
London - London Bridge Research Ethics Committee
REC reference
20/HRA/4580
Date of REC Opinion
30 Oct 2020
REC opinion
Favourable Opinion