A trial looking at giving a third COVID-19 vaccine for people who didn’t have a good response (OCTAVE-DUO)

Cancer type:

All cancer types

Status:

Results

Phase:

Phase 3

This trial looked at giving a 3rd COVID-19 vaccine injection to people whose immune system Open a glossary item wasn’t working well.

The trial was for people with some types of cancer and other ongoing (chronic) health conditions. And their immune response Open a glossary item to the first two vaccines was low.

It was open for people to join between 2021 and 2022. The team published the results in 2024.

More about this trial

Having a chronic health condition such as cancer and treatment for it can affect how well your immune system works. The immune system helps the body fight infections such as COVID-19.

The COVID-19 vaccines work by introducing into the body a harmless piece of the COVID-19 virus called the spike protein. People usually need to have 2 injections to get their immune system to respond well enough to protect them.

For people whose immune system isn’t working very well, the immune response from 2 injections of the vaccine might not be good enough. Researchers hoped that having a 3rd injection might cause a better response from the immune system. This is called a re-boost.

The main aim of this trial was to find out if a re-boost of a COVID-19 vaccine can improve the immune response in people with a chronic health condition.

Summary of results

This trial showed that some people’s immune system responded well to a third COVID-19 vaccine.

Trial design
This trial was for people who had an ongoing (chronic) health condition. This included cancer. A total of 804 people joined this trial, and 785 of those went on to have the vaccine.

Most people were put into 1 of 2 treatment groups at random. Those who’d had a stem cell transplant or CAR T-cell therapy were put into 1 of 3 treatment groups at random. Each group had a different vaccine:

371 people had the Pfizer vaccine (BNT162b2)
363 people had the Moderna vaccine (mRNA-1273)
51 people had the Novavax vaccine (NVX-CoV2373)

People had the vaccine once as an injection into the muscle. They then had a blood test between 21 and 35 days after having the vaccine to see how their immune system had responded.

Results
The research team looked at the number of immune cells in people’s blood samples. They compared the results from samples taken before and after people had the vaccine.

First, they looked at the number of antibodies Open a glossary item .

They found that the number of antibodies increased after the re-boost in:

9 out of 10 people (90%) whose immune system had responded a bit to previous COVID-19 vaccinations
nearly 5 out of 10 people (46%) whose immune system hadn’t responded to previous COVID-19 vaccinations

They also looked at the number of a type of white blood cell called T cells Open a glossary item .

They found that the number of T cells increased after the re-boost in:

just over 8 out of 10 people (80%) whose immune system had responded a bit to previous COVID-19 vaccinations
more than 5 out of 10 people (56%) whose immune system hadn’t responded to previous COVID-19 vaccinations

The Novavax vaccine was only used for people who had a stem cell transplant or CAR T-cell therapy. Researchers found that this vaccine didn’t work as well as the other 2 vaccines.

The trial team looked at why the vaccine didn’t work as well in some people. They think it could have been because they had ongoing health conditions. This includes long term kidney problems, lymphoma, and having treatments that target B cells such as rituximab. They suggest people in this situation need to take extra care to protect themselves from COVID-19.

Side effects
People in all groups had side effects from the vaccine. The most common were:

irregular heartbeat
chest pain
chills
fever
difficulty breathing
fast heart rate
a weakened heart

Most of these were mild or didn’t last long.

Two people had a more serious side effect. These were chest pain and diarrhoea.

No one taking part died because of the vaccine.

Conclusion
The trial team concluded that some people’s immune system that wasn’t working well, responded well to a third COVID-19 vaccine.

The UK Government’s Vaccine Task Force used the results of this trial to help decide how best to give COVID-19 vaccinations. Since September 2021, people with a weaker immune system have been offered a COVID-19 booster vaccine twice a year. This may change in the future depending on further research.

More detailed information
There is more information about this research in the reference below.

Please note, the information we link to here is not in plain English. It has been written for healthcare professionals and researchers.

Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial
C S Goodyear and others
The Lancet Rheumatology, 2024. Volume 6, Issue 6, pages e339 – e351.

Where this information comes from
We have based this summary on the information in the article above. This has been reviewed by independent specialists (peer reviewed Open a glossary item ) and published in a medical journal. We have not analysed the data ourselves. As far as we are aware, the link we list above is active and the article is free and available to view.