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

Phase 3Active Not RecruitingNCT05556720

Monash University960 enrolled

Overview

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

Eligibility

Sex: ALLMin age: 16 Years

Medical Language ↔ Plain English

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)

Locations (13)

St Vincents Hospital

Darlinghurst, New South Wales, Australia

Prince Of Wales Hospital

Randwick, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Royal Brisbane and Womens Hospital

Herston, Queensland, Australia

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Monash Medical Centre

Clayton, Victoria, Australia

St Vincents Hospital

Fitzroy, Victoria, Australia

University Geelong Hospital

Geelong, Victoria, Australia

Austin Hospital

Heidelberg, Victoria, Australia

...and 3 more locations

Outcomes

Primary Outcomes

The geometric mean concentration (GMC) of anti-spike SARS-CoV-2 IgG antibody against SARS-CoV-2

geometric mean concentration (GMC) of anti-spike SARS-CoV-2 IgG (AU/ml)

Time frame: 28 days after completion of trial vaccine/s

Secondary Outcomes

anti-Spike IgG antibody geometric mean concentration

The geometric mean concentration (GMC) (AU/ml) of anti-spike SARS-CoV-2 IgG antibody against SARS-CoV-2 6- and 12-months after completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Seroconversion

The proportion of participants seronegative to SARS-CoV-2 IgG becoming seropositive 1-, 6- and 12-months after completion of trial vaccine/s

Time frame: 1-, 6- and 12-months after completion of trial vaccine/s

Neutralisation responses

Proportion of participants with SARS-CoV-2 neutralising antibody response in each group after 1-, 6- and 12-months post completion of trial vaccine/s, with response defined as either 4-fold rise in the neutralising antibody titre for those with detectable neutralising antibodies at baseline, OR Detectable neutralisation in those with no detectable neutralising antibodies at baseline

Time frame: Up to 12 months post completion of trial vaccine/s

T cell polyfunctionality

Subset analysis and polyfunctionality (number, and concentration of effector cytokines) of SARS-CoV-2 specific T-cell responses at 1-, 6- and 12-months post completion of trial vaccine/s in a subset of participants.

Time frame: Up to 12 months post completion of trial vaccine/s

T lymphocyte responses

Magnitude of SARS-CoV-2 specific T-cell responses at 1-, 6- and 12-months post completion of trial vaccine/s in a subset of participants

Time frame: Up to 12 months post completion of trial vaccine/s

Early local and systemic reactions

Local and systemic reactions assessed by questionnaire on Day 1,2,3,4,5,6 and 7 after randomisation. Solicited and unsolicited adverse events following immunisation (AEFI) up to Day 28. Hospitalisation resulting from adverse events following immunisation (AEFI) up to Day 28.

Time frame: Up to 7 days post completion of trial vaccine/s

Adverse Events Following Immunisation

Proportion with solicited and unsolicited adverse events following immunisation (AEFI) up to Day 28.

Time frame: Up to 28 days post completion of trial vaccine/s

Hospitalisation due to Immunisation

Proportion of participants with hospitalisation resulting from adverse events following immunisation (AEFI) up to Day 28.

Time frame: Up to 28 days post completion of trial vaccine/s

Clinical outcomes - COVID-19 infection

Proportion of patients with PCR-confirmed OR rapid antigen test (RAT) positive SARS-CoV-2 infection in participants up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - Healthcare Attendance Due to COVID-19 infection

Proportion of participants with PCR-confirmed OR rapid antigen test (RAT) positive SARS-CoV-2 infection requiring attendance at a medical facility for assessment and/or hospital admission up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - All Cause and SARS-CoV-2 Related Mortality

Proportion of participants experiencing mortality due to i) any cause and ii) SARS-CoV-2 infection up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - Severity

Proportion of participants needing oxygen therapy and/or ventilatory support due to SARS-CoV-2 infection up to 12-months post completion of trial vaccine/s Need for ICU care due to SARS-CoV-2 infection up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - Severe COVID-19

Proportion of Participants with need for ICU care due to SARS-CoV-2 infection up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - Quality of Life

Quality of life estimates (using EQ-5D-5L survey) at 1-, 6- and 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - Healthcare utilisation

Proportion of participants with healthcare utilisation including outpatient pharmaceutical and medical service use and inpatient hospital admissions related to COVID-19 or study vaccines up to 12-months post completion of trial vaccine/s

Time frame: Up to 12 months post completion of trial vaccine/s

Clinical outcomes - All cause healthcare utilisation

Proportion of participants with healthcare utilisation including outpatient pharmaceutical and medical service use and inpatient hospital admissions

Time frame: Up to 12 months post completion of trial vaccine/s

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

Overview

Conditions

Interventions

Eligibility

Locations (13)

Outcomes

Primary Outcomes

Secondary Outcomes