The Oxford Vaccine Centre COVID-19 Phase I Clinical Trial Explained
What is the purpose of this research study?
The purpose of this study is to test a new vaccine against COVID-19 in healthy volunteers.
This study aims to assess whether healthy people can be protected from COVID-19 with this new vaccine called ChAdOx1 nCoV-19. It will also provide valuable information on safety aspects of the vaccine and its ability to generate good immune responses against the virus.
What is the vaccine being tested?
ChAdOx1 nCoV-19 is made from a virus (ChAdOx1), which is a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees, that has been genetically changed so that it is impossible for it to grow in humans.
Genetic material has been added to the ChAdOx1 construct, that is used to make proteins from the COVID-19 virus (SARS-CoV-2) called Spike glycoprotein (S). This protein is usually found on the surface of SARS-CoV-2 and plays an essential role in the infection pathway of the SARS-CoV-2 virus. The SARS-CoV-2 coronavirus uses its spike protein to bind to ACE2 receptors on human cells to gain entry to the cells and cause an infection.
By vaccinating with ChAdOx1 nCoV-19, we are hoping to make the body recognise and develop an immune response to the Spike protein that will help stop the SARS-CoV-2 virus from entering human cells and therefore prevent infection.
Vaccines made from the ChAdOx1 virus have been given to more than 320 people to date and have been shown to be safe and well tolerated, although they can cause temporary side effects, such as a temperature, headache or sore arm.
What does the study involve?
Up to 1102 participants will be recruited across multiple study sites in Oxford, Southampton, London and Bristol. These participants will be randomly allocated to receive either the ChAdOx1 nCoV-19 vaccine or a licensed vaccine (MenACWY) that will be used as a ‘control’ for comparison.
At the start of the trial we will also recruit a separate small group of 10 volunteers who will receive 2 doses of ChAdOx1 nCoV-19 four weeks apart.
What is the MenACWY vaccine?
The MenACWY vaccine is a licensed vaccine against group A, C, W and Y meningococcus which has been given routinely to teenagers in the UK since 2015 and protects against one of the most common causes of meningitis and sepsis. This vaccine is also given as a travel vaccine for high risk countries.
The MenACWY vaccine is being used as an ‘active control’ vaccine in this study, to help us understand participants’ response to ChAdOx1 nCoV-19. The reason for using this vaccine, rather than a saline control, is because we expect to see some minor side effects from the ChAdOx1 nCOV-19 vaccine such as a sore arm, headache and fever. Saline does not cause any of these side effects. If participants were to receive only this vaccine or a saline control, and went on to develop side effects, they would be aware that they had received the new vaccine. It is critical for this study that participants remain blinded to whether or not they have received the vaccine, as, if they knew, this could affect their health behaviour in the community following vaccination, and may lead to a bias in the results of the study.
Who can take part in the study?
Participants must NOT:
Be aged 18-55 years old
Have tested positive for COVID-19
Be in good health
Be pregnant, intending to become pregnant, or breastfeeding during the study
Based in one of the recruiting areas
Have previously taken part in a trial with an adenoviral vaccine or received any other coronavirus vaccines
Full inclusion and exclusion criteria is provided in the participant information sheet.
How will the trial work?
The main focus of the study is to find out if this vaccine is going to work against COVID-19, if it won’t cause unacceptable side effects and if it induces good immune responses. The dose used in this trial was chosen based on previous experiences with other ChAdOx1 based vaccines.
Study participants will not know whether they have received the ChAdOx1 nCoV-19 vaccine until the end of the trial.
The first few days of vaccinations will be planned as follows:
The first two participants will be vaccinated, one with the ChAdOx1 nCoV-19 vaccine and one with the control vaccine.
Participants monitored for 48 hours.
A further six participants will be vaccinated, three with the ChAdOx1 nCoV-19 vaccine and three with the control vaccine.
Participants monitored for 48 hours.
Progress to vaccinating larger numbers of participants.
What about after the vaccination?
Participants will be given an E-diary to record any symptoms experienced for 7 days after receiving the vaccine. They will also record if they feel unwell for the following three weeks.
Following vaccination, participants will attend a series of follow-up visits. During these visits, the team will check participants’ observations, take a blood sample and review the competed E-diary. These blood samples will be used to assess the immune response to the vaccine.
If participants develop COVID-19 symptoms during the study, they can contact a member of the clinical team, and we will assess them to check whether they have become infected with the virus. If a participant was very unwell, we would call our colleagues in the hospital and ask them to review the volunteer if appropriate.
When will the results be available?
To assess whether the vaccine works to protect from COVID-19, the statisticians in our team will compare the number of infections in the control group with the number of infections in the vaccinated group. For this purpose, it is necessary for a small number of study participants to develop COVID-19. How quickly we reach the numbers required will depend on the levels of virus transmission in the community. If transmission remains high, we may get enough data in a couple of months to see if the vaccine works, but if transmission levels drop, this could take up to 6 months.
What if it doesn’t work?
A high proportion of vaccines are found not to be promising even before clinical trials. Moreover, a significant proportion of vaccines that are tested in clinical trials don’t work. If we are unable to show that the vaccine is protective against the virus, we would review progress, examine alternative approaches, such as using different numbers of doses, and would potentially stop the programme.
Author: Dr Tonia Thomas, Oxford Vaccine Group