Ignite Creation Date:
2024-10-25 @ 7:55 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06599658
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-11
Brief Title:
COVID-19 Booster and IIV Schedule in Immunocompromised Hosts
Sponsor:
None
Organization:
None
Study Overview
Official Title:
The Immunogenicity and Safety of COVID-19 and Influenza Vaccine Co-administration and Interval in Immunocompromised Hosts
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CO2I2
Brief Summary:
The goal of this pragmatic embedded open-label 2 x 2 factorial phase II randomized controlled trial is to evaluate strategies to improve COVID-19 booster and influenza vaccine immunogenicity in people living with immunocompromising conditions PLIC
The main questions it aims to answer are
1 Is co-administration of seasonal inactivated influenza vaccine IIV with the most up-to-date recommended COVID-19 booster dose non-inferior in inducing a 1-month peak protective humoral response against COVID-19 compared to a strategy of sequential administration of COVID-19 booster dose followed by seasonal IIV given one month later
2 Is the administration of the most up-to-date recommended COVID-19 booster doses at 3-month intervals superior at maintaining a longer term protective humoral immune response compared to booster doses administered at 6-month intervals
Researchers will compare 1 COVID-19 and Influenza vaccines administered at Day 0 COVID-19 Booster at a 3-month interval 2 COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 COVID-19 Booster at a 3-month interval 3 COVID-19 and Influenza vaccines administered at Day 0 COVID-19 Booster at a 6-month interval and 4 COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 COVID-19 Booster at a 6-month interval to see if median neutralization capacity of patient sera is non-inferior in the co- vs sequential administration arms at 1-month after the initial COVID-19 booster and superior in the 3-month interval arms vs the 6-month interval arms at 12 months after the initial COVID-19 booster These outcomes will also be compared at 2-months for question 1 and 6-months for question 2
People living with immunocompromising conditions who take part in the trial will have blood samples drawn to verify immune response be monitored for changes in clinical events and therapies and complete questionnaires to verify adverse effects quality of life and economic impact
The main questions it aims to answer are
1 Is co-administration of seasonal inactivated influenza vaccine IIV with the most up-to-date recommended COVID-19 booster dose non-inferior in inducing a 1-month peak protective humoral response against COVID-19 compared to a strategy of sequential administration of COVID-19 booster dose followed by seasonal IIV given one month later
2 Is the administration of the most up-to-date recommended COVID-19 booster doses at 3-month intervals superior at maintaining a longer term protective humoral immune response compared to booster doses administered at 6-month intervals
Researchers will compare 1 COVID-19 and Influenza vaccines administered at Day 0 COVID-19 Booster at a 3-month interval 2 COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 COVID-19 Booster at a 3-month interval 3 COVID-19 and Influenza vaccines administered at Day 0 COVID-19 Booster at a 6-month interval and 4 COVID-19 vaccine administered at Day 0 and Influenza vaccine administered at Day 28 COVID-19 Booster at a 6-month interval to see if median neutralization capacity of patient sera is non-inferior in the co- vs sequential administration arms at 1-month after the initial COVID-19 booster and superior in the 3-month interval arms vs the 6-month interval arms at 12 months after the initial COVID-19 booster These outcomes will also be compared at 2-months for question 1 and 6-months for question 2
People living with immunocompromising conditions who take part in the trial will have blood samples drawn to verify immune response be monitored for changes in clinical events and therapies and complete questionnaires to verify adverse effects quality of life and economic impact
Detailed Description:
Background
People living with immunocompromising conditions PLIC are more susceptible to complications related to respiratory infections According to Statistics Canada data in 2020 approximately 14 of Canadians aged 15 years or older suffered from a compromised immune system PLIC eg solid organ transplant SOT recipients people living with human immunodeficiency viruses PLWH inflammatory bowel disease IBD or systemic autoimmune rheumatic diseases RD are at risk for experiencing a wide range of respiratory infections A recent North American study assessed the socioeconomic burden associated with immunocompromising conditions MarketScan datasets from 2017-2021 showed that PLIC accounted for 32 of hospitalizations for acute respiratory infections representing a 5-8-fold higher risk than in non-immunocompromised hosts
PLIC are at elevated risk of severe infection and death from COVID-19 increasing burden to patients and healthcare systems Often including members of diverse ethnocultural origin PLIC have also been among the most significantly affected by the COVID-19 pandemic Vaccination is the most effective way to reduce the severity respiratory disease and infection-associated complications in the general population Yet suboptimal immune status results in a higher risk for COVID-19-related hospitalization up to 13-fold and death up to 19-fold compared with the general population in many PLIC with substantial implications for healthcare burden and costs despite PLIC comprising but a minority of the overall population
Immunogenicity and protection from severe disease can be improved in PLIC with COVID-19 booster doses A systematic review by the COVID-19 evidence network found that PLIC were more susceptible to severe infections and hospitalizations with emerging variants when compared with the general public This was attributed to immunomodulatory agents eg calcineurin inhibitors antimetabolites steroids cytotoxic therapy biological response modifiers impairing the formation of memory T cells decreasing cellular-mediated immune responses and limiting capacity to seroconvert and sustain protective immune memory responses For example a meta-analysis in SOT found seroconversion and cellular response rates of 392 95 confidence interval CI 333-453 and 416 95 CI 300-536 respectively after the primary series in solid organ transplant SOT
As the pandemic progressed it was observed that three or four doses of COVID-19 vaccines increased immunogenicity and protected against severe disease requiring hospitalization with antibody response being most pronounced in the presence of hybrid immunity arising when SARS-CoV-2 infection was paired with multiple vaccinations Importantly decreased immunogenicity has been observed in PLIC in relation to other vaccines such as the Inactivated Influenza Vaccine IIV warranting high-dose HD IIV administration to accomplish seroconversion
Rationale
The increased risk of COVID-19 and influenza alongside adverse outcomes of respiratory infections in PLIC and the variability in vaccine responses highlight the need for optimizing immunogenicity and elucidating the mechanisms underlying blunted andor less durable vaccine responses in PLIC
Correlates of protective humoral immunity and COVID-19 disease severity Antigen-binding antibodies as well as neutralizing antibodies have been proposed as independent correlates of protection from SARS-CoV-2 infections The WHO expert committee consensus defined anti-SARS-CoV-2-S1-Receptor-Binding Domain IgG of BAUmL as low concentrations 200-300 BAUmL as mid-range concentrations and 700-800 BAUmL as high concentrations PLIC demonstrated a reduced capacity to mount protective antibody responses Yet additional doses resulted in higher antibody concentrations A recent analysis by De Serres and team demonstrated antibody levels in the range of 700-1200 BAUml conferred protection as measured by a surrogate virus neutralization test sVNT threshold of 30 against Omicron Taken together this body of evidence suggests that neutralizing or binding anti-S could serve as correlates for protection Importantly humoral correlates of protection need to also be evaluated for emerging viral variants especially those which have acquired immune-evasion properties Moreover in addition to humoral immunity spike-specific CD4 and CD8 T cells are also critical for vaccine-induced protection and are active contributors to global correlates of protection in many individuals
Correlates of protective cellular immunity The identification of correlates of cellular immunity capable of informing clinical care has been hampered by a paucity of rapid antigen-specific cellular immunity assays alongside increased costs and time demands Activation-induced marker AIM assays wherein antigen-specific T cell subsets are enumerated in peripheral blood mononuclear cells PBMC identified by their upregulation of AIM eg CD40L 4-1BB CD69 are effective at quantifying virus antigen-reactive T cells However the rarity of these cells seldom conveys the quality and functional fate of antigen-specific T cell subsets contributing to the global cellular response Whether AIM phenotypes could be implemented as rapid assays of cellular immunity and exploited towards clinical decision-making warrants further study
The trial will provide evidence to guide health policy in a highly diverse and vulnerable subpopulations of PLIC More specifically the trial will inform the preferred vaccine schedule for COVID-19 and IIV in these patients potentially improving upon vaccine acceptance adherence and protection eventually improving burden to patients caretakers and the health care system
Primary Objectives
1 To assess whether co-administration of seasonal inactivated influenza vaccine IIV with the most up-to-date recommended COVID-19 booster dose is non-inferior in inducing a 1-month peak protective humoral response against COVID-19 compared to a strategy of sequential administration of COVID-19 booster dose followed by seasonal IIV given one month later
It is hypothesized that the co-administration strategy will be non-inferior to the sequential strategy in inducing a peak 1-month SARS-CoV-2-specific neutralizing antibody response in PLIC It will also be less costly with no increase in adverse effects and no detrimental effect on response to seasonal IIV as measured by hemagglutination inhibition
2 To assess whether the administration of the most up-to-date recommended COVID-19 booster doses at 3-month intervals is superior at maintaining a longer term protective humoral immune response compared to booster doses administered at 6-month intervals
It is hypothesized that the 3-month booster strategy will be superior to the 6-month strategy in inducing a SARS-CoV-2--specific neutralizing antibody response that is sustained for 12 months without increasing adverse effects or disease-specific complications
People living with immunocompromising conditions PLIC are more susceptible to complications related to respiratory infections According to Statistics Canada data in 2020 approximately 14 of Canadians aged 15 years or older suffered from a compromised immune system PLIC eg solid organ transplant SOT recipients people living with human immunodeficiency viruses PLWH inflammatory bowel disease IBD or systemic autoimmune rheumatic diseases RD are at risk for experiencing a wide range of respiratory infections A recent North American study assessed the socioeconomic burden associated with immunocompromising conditions MarketScan datasets from 2017-2021 showed that PLIC accounted for 32 of hospitalizations for acute respiratory infections representing a 5-8-fold higher risk than in non-immunocompromised hosts
PLIC are at elevated risk of severe infection and death from COVID-19 increasing burden to patients and healthcare systems Often including members of diverse ethnocultural origin PLIC have also been among the most significantly affected by the COVID-19 pandemic Vaccination is the most effective way to reduce the severity respiratory disease and infection-associated complications in the general population Yet suboptimal immune status results in a higher risk for COVID-19-related hospitalization up to 13-fold and death up to 19-fold compared with the general population in many PLIC with substantial implications for healthcare burden and costs despite PLIC comprising but a minority of the overall population
Immunogenicity and protection from severe disease can be improved in PLIC with COVID-19 booster doses A systematic review by the COVID-19 evidence network found that PLIC were more susceptible to severe infections and hospitalizations with emerging variants when compared with the general public This was attributed to immunomodulatory agents eg calcineurin inhibitors antimetabolites steroids cytotoxic therapy biological response modifiers impairing the formation of memory T cells decreasing cellular-mediated immune responses and limiting capacity to seroconvert and sustain protective immune memory responses For example a meta-analysis in SOT found seroconversion and cellular response rates of 392 95 confidence interval CI 333-453 and 416 95 CI 300-536 respectively after the primary series in solid organ transplant SOT
As the pandemic progressed it was observed that three or four doses of COVID-19 vaccines increased immunogenicity and protected against severe disease requiring hospitalization with antibody response being most pronounced in the presence of hybrid immunity arising when SARS-CoV-2 infection was paired with multiple vaccinations Importantly decreased immunogenicity has been observed in PLIC in relation to other vaccines such as the Inactivated Influenza Vaccine IIV warranting high-dose HD IIV administration to accomplish seroconversion
Rationale
The increased risk of COVID-19 and influenza alongside adverse outcomes of respiratory infections in PLIC and the variability in vaccine responses highlight the need for optimizing immunogenicity and elucidating the mechanisms underlying blunted andor less durable vaccine responses in PLIC
Correlates of protective humoral immunity and COVID-19 disease severity Antigen-binding antibodies as well as neutralizing antibodies have been proposed as independent correlates of protection from SARS-CoV-2 infections The WHO expert committee consensus defined anti-SARS-CoV-2-S1-Receptor-Binding Domain IgG of BAUmL as low concentrations 200-300 BAUmL as mid-range concentrations and 700-800 BAUmL as high concentrations PLIC demonstrated a reduced capacity to mount protective antibody responses Yet additional doses resulted in higher antibody concentrations A recent analysis by De Serres and team demonstrated antibody levels in the range of 700-1200 BAUml conferred protection as measured by a surrogate virus neutralization test sVNT threshold of 30 against Omicron Taken together this body of evidence suggests that neutralizing or binding anti-S could serve as correlates for protection Importantly humoral correlates of protection need to also be evaluated for emerging viral variants especially those which have acquired immune-evasion properties Moreover in addition to humoral immunity spike-specific CD4 and CD8 T cells are also critical for vaccine-induced protection and are active contributors to global correlates of protection in many individuals
Correlates of protective cellular immunity The identification of correlates of cellular immunity capable of informing clinical care has been hampered by a paucity of rapid antigen-specific cellular immunity assays alongside increased costs and time demands Activation-induced marker AIM assays wherein antigen-specific T cell subsets are enumerated in peripheral blood mononuclear cells PBMC identified by their upregulation of AIM eg CD40L 4-1BB CD69 are effective at quantifying virus antigen-reactive T cells However the rarity of these cells seldom conveys the quality and functional fate of antigen-specific T cell subsets contributing to the global cellular response Whether AIM phenotypes could be implemented as rapid assays of cellular immunity and exploited towards clinical decision-making warrants further study
The trial will provide evidence to guide health policy in a highly diverse and vulnerable subpopulations of PLIC More specifically the trial will inform the preferred vaccine schedule for COVID-19 and IIV in these patients potentially improving upon vaccine acceptance adherence and protection eventually improving burden to patients caretakers and the health care system
Primary Objectives
1 To assess whether co-administration of seasonal inactivated influenza vaccine IIV with the most up-to-date recommended COVID-19 booster dose is non-inferior in inducing a 1-month peak protective humoral response against COVID-19 compared to a strategy of sequential administration of COVID-19 booster dose followed by seasonal IIV given one month later
It is hypothesized that the co-administration strategy will be non-inferior to the sequential strategy in inducing a peak 1-month SARS-CoV-2-specific neutralizing antibody response in PLIC It will also be less costly with no increase in adverse effects and no detrimental effect on response to seasonal IIV as measured by hemagglutination inhibition
2 To assess whether the administration of the most up-to-date recommended COVID-19 booster doses at 3-month intervals is superior at maintaining a longer term protective humoral immune response compared to booster doses administered at 6-month intervals
It is hypothesized that the 3-month booster strategy will be superior to the 6-month strategy in inducing a SARS-CoV-2--specific neutralizing antibody response that is sustained for 12 months without increasing adverse effects or disease-specific complications
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None