Clinical trial NCT05556720: Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
Official title: Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: HIV
Organ Transplantation
Lymphoma, Non-Hodgkin
Chronic Lymphocytic Leukemia
Multiple Myeloma
COVID-19 Vaccines
Lead sponsor: Bayside Health
Sponsor class: OTHER_GOV
Collaborators: name: Monash University
First posted: 2022-09-27
Enrollment: 960
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study participants who have received three to six doses of Australian TGA approved COVID-19 vaccine will be randomised into one of up to three groups, who will be administered either one or two homologous doses of bivalent COVID-19 vaccines, e.g. bivalent Moderna mRNA vaccine OR bivalent Pfizer mRNA vaccine, using a central computer-generated random allocation algorithm, with random block sizes of 3 or 6.

Randomisation will be stratified by:

- Study subgroup (HIV, solid organ transplant, haematological malignancy)
Primary purpose: TREATMENT

Brief summary: 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.

BOOST-IC is an adaptive randomised clinical trial (RCT) to assess the immunogenicity and safety of additional 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.

Detailed description: 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 6-doses of Australian TGA approved COVID-19 vaccines (BA.4/5 Moderna and Pfizer vaccines) will be randomised 1:1 to receive either one or two doses of a bivalent COVID-19 vaccine, as these become available in Australia. And 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 bivalent Moderna or Pfizer COVID-19 vaccine. As additional bivalent 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

Eligibility criteria: Inclusion Criteria:

* Able to give informed consent and undertake study procedures
* Age ≥16 years old
* Have completed at least 3 months prior, 3- to 6-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 led less than 3 or more than 6 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

Primary outcomes:
measure: The geometric mean concentration (GMC) of anti-spike SARS-CoV-2 IgG antibody against SARS-CoV-2
timeFrame: 28 days after completion of trial vaccine/s
Secondary outcomes:
measure: anti-Spike IgG antibody geometric mean concentration
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Seroconversion
timeFrame: 1-, 6- and 12-months after completion of trial vaccine/s
measure: Neutralisation responses
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: T cell polyfunctionality
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: T lymphocyte responses
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Early local and systemic reactions
timeFrame: Up to 7 days post completion of trial vaccine/s
measure: Adverse Events Following Immunisation
timeFrame: Up to 28 days post completion of trial vaccine/s
measure: Hospitalisation due to Immunisation
timeFrame: Up to 28 days post completion of trial vaccine/s
measure: Clinical outcomes - COVID-19 infection
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - Healthcare Attendance Due to COVID-19 infection
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - All Cause and SARS-CoV-2 Related Mortality
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - Severity
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - Severe COVID-19
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - Quality of Life
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - Healthcare utilisation
timeFrame: Up to 12 months post completion of trial vaccine/s
measure: Clinical outcomes - All cause healthcare utilisation
timeFrame: Up to 12 months post completion of trial vaccine/s
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
Study officials:
affiliation: Alfred Hospital, Melbourne, Australia
name: James H McMahon, MBBS PhD
role: PRINCIPAL_INVESTIGATOR
References: