Observational Cohort Trial -T-cells Antibodies and Vaccine Efficacy in SARS-CoV-2

"COVID-19 vaccines have been shown to work well in protecting against COVID-19 infection, although studies have mainly been in people without significant health problems. The OCTAVE trial is investigating whether people with health problems or treatments that affect their immune system are also protected by COVID-19 vaccines. The vaccines work by stimulating the body’s immune system to produce antibodies that can protect against COVID-19 infection.

The OCTAVE trial has recruited patients with diseases or treatments that supress the immune system, including some types of cancers, rheumatoid arthritis, psoriatic arthritis, ANCA-Associated Vasculitis (AVV), inflammatory bowel disease, chronic liver disease, kidney disease, stem cell transplant and chimeric antigen receptor (CAR) T recipients. Participants received the Pfizer/BioNTech or Astra Zeneca vaccine as part of the National UK COVID-19 vaccination programme. Blood samples were taken around 4 weeks after the second vaccine dose to measure the antibodies that should be increased by the vaccine. These antibodies work against the coronavirus spike protein (a protein on the surface of the virus that helps it invade human cells) and are called “Anti-S antibodies”.

The OCTAVE trial is not yet completed but has recruited 2,592 patients so far. We are still collecting data and testing the blood samples, so not all the information has been analysed yet. However, we do have some early and preliminary results on 600 patients that we want to share. We also compared our results with the results from another study (called PITCH) of people without health problems.

• More than 83% of participants in all groups had detectable anti-S antibodies 4 weeks after their second vaccine, with the exception of the AAV group receiving rituximab treatment where only a quarter showed an antibody response.
• Overall, almost 90% of the participants tested had detectable anti-S antibodies after their two vaccines. In comparison, 100% of the healthy people in the PITCH study had antibodies after their two vaccines.
• We also found that, depending on the type of disease or treatment, the levels of anti-S antibodies were lower in OCTAVE participants than the levels seen in the healthy PITCH participants.
• Interestingly, most participants had a similar response to healthy individuals in another part of their immune system (T cells) to the coronavirus spike protein.

No one knows yet what level of antibody is needed to protect against severe COVID-19 infection.

We are continuing to collect and analyse our data in more detail to confirm these findings and see if we can identify factors, including specific treatments that are linked with lower response to vaccines. Our results support the need to investigate further vaccination strategies to improve the immune responses against COVID-19 in patients whose immune systems are affected by illness or the treatments they receive.

We have already started a new trial called OCTAVE-DUO, which will test whether giving a top-up vaccination will stimulate a better antibody response in those people with a low antibody response after two doses."

OCTAVE Trial_Lay summary preliminary results v1.0, 10-Sep-2021

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Randomised Trial Optimising COVID-19 Vaccination in Patients with Chronic Health Conditions and a Poor Response to Standard Vaccination

Background

To date, more than 43 million people have been fully vaccinated with 2 doses in the UK. Research studies have shown that two doses of vaccine prevent COVID-19 infection in up to 90% of people. However, these vaccines were tested in predominantly healthy people. Recent research in individuals with chronic health problems or cancer, suggest that approximately 40% of patients who are immune compromised, either because of a chronic health condition or the treatment they are receiving, generate low or no detectable antibody or T-cells (a type of white blood cell) after two doses of the Pfizer or AstraZeneca COVID-19 vaccines. This raises the question of the potential benefit of a third primary dose of vaccine (called a top-up) in vulnerable patients with inadequate immune responses. This strategy has been successfully used for other vaccines but the limited research performed to date for COVID-19 has given variable results, so additional research is needed.

Aim

The OCTAVE-DUO trial aims to find out whether a third primary dose of the vaccine for COVID-19 can help generate a better immune response in immune compromised patients with chronic health conditions or cancer.

Trial Eligibility Criteria (suitablity)

The OCTAVE-DUO trial is for patients aged 18 years or over with one or more of the following health conditions: breast or lung cancer; certain types of blood cancer; immune-mediated rheumatic diseases (e.g. rheumatoid arthritis); chronic kidney disease; chronic liver disease; inflammatory bowel disease on immune suppressive therapy; stem cell transplant; and primary immunodeficiency (a group of disorders characterised by poor or absent immune function).

Patients must have no or an inadequate immune response to 2 doses of COVID-19 vaccine and there should be no other reason why the patient cannot receive the vaccine.

For the blood-cancer sub-study, pregnant women are excluded and women of childbearing age must agree to use contraceptive measures.

Randomisation and Trial Treatment

Main Study Randomisation

Participants in the main study are randomised to receive the Pfizer or Moderna COVID-19 vaccines intramuscularly at the approved dose for that vaccine.

Sub-study Randomisation

Participants with blood cancer are randomised to receive Pfizer or Moderna or Novavax (a new vaccine which is not yet authorised for use) COVID-19 vaccines intramuscularly at the approved dose for that vaccine.

Sample and Data Collection

Blood samples are collected prior to and at 21 days after the top-up vaccine.

Relevant clinical data will be collected including: type of disease, treatments received, and whether the participant goes onto catch COVID-19.

Follow-up

Participants will be followed up for 3-months after re-vaccination. Long term follow-up is planned by data linkage with national datasets.

Analysis

Samples will be analysed in laboratories around the UK. The results of these laboratory tests and the clinical data will then be analysed and the results published. The analysis will look at the population as a whole

A lay summary of the results will be posted on the trial website.

Number of Patients

Total: Up to 1200 (recruitment targets vary per disease cohort).

Duration

Patients are expected to be recruited over a 3-month period and followed up for 3 months.

Contacts

Sponsor: University of Birmingham
Chief Investigator: Professor Iain McInnes, University of Glasgow
OCTAVE Trial Office: Cancer Research UK Clinical Trials Unit (CRCTU), University of Birmingham, Edgbaston, Birmingham, B15 2TT

 

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