Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial

Despite the greater risk of adverse COVID-19 outcomes, antibody and cell-mediated immune responses to COVID-19 vaccines vary amongst immunocompromised (IC) people and are poorly defined. IC hosts were largely excluded from the COVID-19 vaccine registration trials, though many countries recommend additional and booster doses of vaccination in this group. However, data are heterogeneous, in part due the variable nature of immunodeficiencies in IC groups and non-standardised outcome measures used in studies.

BOOST-IC is an adaptive randomised clinical trial (RCT) to assess the immunogenicity and safety of additional bivalent COVID-19 vaccine doses in immunocompromised (IC) people, including people with HIV, solid organ transplants (SOT) recipients or those with haematological malignancies. Briefly, the study aims to generate high-quality evidence on the immunogenicity and safety of alternative COVID-19 booster strategies against SARS-CoV-2 for IC people in Australia.

To do this, participants who have previously completed 3- to 8-doses of Australian TGA approved COVID-19 vaccines (Moderna and Pfizer vaccines) will be randomised 1:1 to receive either one or two doses of the current TGA approved COVID-19 vaccine. .An additional arm can be added if an additional suitable vaccine becomes available. Namely, patients will be randomised to receive either one or two doses of Moderna or Pfizer COVID-19 vaccine. As additional COVID-19 vaccines become available in Australia, these will be included in the trial, as additional arms. The trial can incorporate up to three arms at one time.

Patients will be followed up for 455 days post randomisation. Specific study questions pertain to:

• examining how additional doses of COVID-19 vaccine/s affect correlates of protective immunity
• examining the safety of additional doses of COVID-19 vaccine/s
• characterising the humoral and cellular immune responses to COVID-19 vaccination receiving 1 or 2 booster doses of COVID-19 vaccine/s

Inclusion criteria

• Able to give informed consent and undertake study procedures
• Age ≥16 years old
• Have completed at least 3 months prior, 3- to 8-doses of an Australian TGA approved SARS-CoV-2 vaccine (including mRNA [Pfizer or Moderna], ChAdOx1 [Oxford/Astra Zeneca] or protein [Novavax])
• Fit the criteria to be included in one of the following 3 populations: Infected with HIV; Current recipient of a solid organ transplant including: kidney, pancreas, liver, malignancy episodes of severe rejection requiring T- or B-cell depleting agents in the prior 3 months; Undergoing chemotherapy, immunotherapy and/or targeted therapy, or completed in the last 2 years for: chronic lymphocytic leukemia, multiple myeloma or non-Hodgkin lymphoma.

Exclusion criteria

• Are contraindicated to receive a COVID-19 booster vaccination, e.g. history of anaphylaxis to a vaccine component or myocarditis attributed to previous receipt of an mRNA vaccine.
• Has had less than 3 or more than 8 doses of COVID-19 vaccine
• Is on another clinical trial investigating alternate COVID-19 vaccination schedules or investigational drugs to prevent or treat COVID-19
• Life expectancy < 12 months, or enrolment deemed not in the best interest of the patient
• Unable to provide informed consent
• Receipt of SARS-CoV-2 specific monoclonal antibodies in the 3 months prior to receiving the first dose of study vaccine
• Acute respiratory tract infection and/or temperature > 38 degrees centigrade on day of receiving first dose of study vaccine
• History of autologous stem cell transplant in the prior 6 months or history of ever having an allogeneic stem cell transplant or CAR T-cell therapy
• Have not received another licensed vaccine in the 7 days before or 7 days after the day of receiving the COVID-19 study vaccine (NOTE: Participants can receive another licensed vaccine on the same day as the COVID-19 vaccine)