COVID-19 Booster + Flu Vaccine for Immunocompromised People

(CO2I2 Trial)

Overseen By Ruth Sapir-Pichhadze, B.Med.Sc, MD, MSc, PhD, FRCPC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre

Must be taking: Immunosuppressive agents

Must not be taking: Intravenous immunoglobulins, Chemotherapy

Disqualifiers: Recent vaccines, Guillain-Barre, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 12 months

660 Participants Needed

Trial Summary

Do I have to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it seems that participants with certain immunocompromising conditions who are on maintenance immunosuppressive treatments are eligible, suggesting you may not need to stop your current meds. It's best to discuss with the trial coordinators for specific guidance.

What data supports the idea that COVID-19 Booster + Flu Vaccine for Immunocompromised People is an effective treatment?

The available research does not provide any data on the effectiveness of the COVID-19 Booster + Flu Vaccine for Immunocompromised People. Instead, the studies focus on treatments for rheumatoid arthritis, comparing different drugs like tocilizumab, abatacept, and others. Therefore, there is no information here to support the effectiveness of the COVID-19 Booster + Flu Vaccine for Immunocompromised People. ^{1 2 3 4 5}

What safety data exists for COVID-19 and flu vaccines for immunocompromised people?

The safety data for COVID-19 vaccines, including Pfizer-BioNTech, Moderna, and Johnson & Johnson's Janssen, has been extensively studied and reported in various research articles. These studies have analyzed adverse events reported in systems like the Vaccine Adverse Event Reporting System (VAERS) in the United States and similar systems in other countries like Korea. The studies generally show that these vaccines have a well-documented safety profile, with adverse events being monitored and reported since their emergency use authorization. However, specific safety data for the combination of COVID-19 booster and flu vaccines, particularly for immunocompromised individuals, may not be directly addressed in the provided research. It is important for participants to consult with healthcare providers for personalized advice and to consider ongoing clinical trials that may provide more specific safety data for this combination in immunocompromised populations. ^{6 7 8 9 10}

Is the COVID-19 vaccine a promising treatment for immunocompromised people?

Yes, the COVID-19 vaccine is promising for immunocompromised people. Although their initial response might be weaker, a booster dose can significantly improve their immune response, making the vaccine effective for them. ^{11 12 13 14 15}

What is the purpose of this trial?

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.

Eligibility Criteria

This trial is for people with conditions like HIV, lupus, or rheumatoid arthritis that weaken their immune system. It's also for those who've had an organ transplant. Participants should be due for a COVID-19 booster and flu shot but can't join if they have certain health issues that aren't listed here.

Inclusion Criteria

Have at least one of the following immunocompromising conditions: a) Received a solid organ transplant (SOT) ≥3-months ago, and treated with a conventional maintenance immunosuppression regimen; b) People living with HIV (PLWH) receiving ART for ≥6 months who meet at least one of the specified conditions; c) Inflammatory bowel disease (IBD) treated with a conventional or biologic immunosuppressive agent for ≥3 months; d) Rheumatoid arthritis or systemic lupus erythematosus (herein referred to as rheumatological disease (RD)) treated with a conventional or biologic immunosuppressive agent for ≥3 months.

I have received at least 3 doses of the mRNA COVID-19 vaccine.

Exclusion Criteria

I cannot receive vaccines by injection due to a bleeding disorder or very low platelet count.

I have not received chemotherapy like cyclophosphamide in the last 6 months.

Received annual vaccination against influenza < 6 months ago

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive COVID-19 and Influenza vaccines with varying schedules to assess immunogenicity and safety

12 months

Visits at baseline, 1, 2, 3, 4, 6, 7, 9, 10, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• COVID-19 Vaccines
• Inactivated influenza vaccine (IIV)

Trial Overview The study tests how well the body responds to different schedules of COVID-19 boosters and flu shots in immunocompromised individuals. It checks if giving both vaccines together works as well as spacing them out, and whether getting COVID-19 boosters every 3 months is better than every 6 months.

Participant Groups

Group I: Group 4 Experimental Treatment 2 Interventions

Covid-19 booster every 6 months and IIV at 1 month

Group II: Group 3 Experimental Treatment 2 Interventions

Covid-19 booster every 6 months and IIV at baseline

Group III: Group 2 Experimental Treatment 2 Interventions

Covid-19 booster every 3 months and IIV at 1 month

Group IV: Group 1 Experimental Treatment 2 Interventions

Covid-19 booster every 3 months and Inactivated influenza vaccine (IIV) at baseline

COVID-19 Vaccines is already approved in United States, European Union for the following indications:

Approved in United States as Pfizer-BioNTech COVID-19 Vaccine for:

• Prevention of COVID-19 in individuals 6 months of age and older

Approved in United States as Moderna COVID-19 Vaccine for:

• Prevention of COVID-19 in individuals 6 months of age and older

Approved in United States as Novavax COVID-19 Vaccine for:

• Prevention of COVID-19 in individuals 12 years of age and older

Approved in European Union as Comirnaty for:

• Prevention of COVID-19 in individuals 6 months of age and older

Approved in European Union as Spikevax for:

• Prevention of COVID-19 in individuals 6 months of age and older

Approved in European Union as Nuvaxovid for:

• Prevention of COVID-19 in individuals 12 years of age and older

Who Is Running the Clinical Trial?

McGill University Health Centre/Research Institute of the McGill University Health Centre

Lead Sponsor

Trials

476

Recruited

170,000+

Findings from Research

In a study of 132 women with active rheumatoid arthritis who did not respond to anti-TNF therapy, both tocilizumab and abatacept significantly reduced disease activity over 24 weeks, as measured by the DAS28-ESR score.

While both treatments were effective, abatacept demonstrated a better safety profile, with fewer adverse effects and more favorable laboratory results compared to tocilizumab, which was associated with declines in hemoglobin and neutrophil counts, as well as increases in blood pressure and liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of intravenous tocilizumab versus intravenous abatacept in treating female Saudi Arabian patients with active moderate-to-severe rheumatoid arthritis. Elmedany, SH., Mohamed, AE., Galil, SMA.[2020]

In the AVERT-2 study, 22% of patients treated with abatacept plus methotrexate achieved remission at week 24, and a significant proportion (56% for SDAI remission) maintained this response through week 52, indicating the efficacy of this combination therapy in early rheumatoid arthritis.

Patients who continued on weekly abatacept treatment during the de-escalation period had higher rates of sustained remission compared to those who de-escalated or withdrew abatacept, suggesting that ongoing treatment may be beneficial for maintaining remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study. Emery, P., Tanaka, Y., Bykerk, VP., et al.[2023]

Tocilizumab, either alone or in combination with methotrexate, showed superior effectiveness in treating rheumatoid arthritis compared to standard care and methotrexate alone, with significant improvements in ACR response rates at 26 weeks based on a network meta-analysis of 68 randomized controlled trials involving 207 articles.

The study found that tocilizumab's effectiveness was comparable to other biologics, indicating it is a viable treatment option for patients with rheumatoid arthritis who have not responded to conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis. Alfonso-Cristancho, R., Armstrong, N., Arjunji, R., et al.[2021]

Abatacept is a targeted treatment for rheumatoid arthritis (RA) that works by blocking the interaction between antigen-presenting cells and T-cells, leading to reduced T-cell activation and improved immune regulation.

In RA patients, abatacept has been shown to effectively decrease symptoms such as arthritis, pain, and fatigue, while also reducing joint damage, making it a valuable option for achieving lasting remissions or low disease activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting lymphocyte activation to treat rheumatoid arthritis. Falgarone, G., Semerano, L., Rullé, S., et al.[2020]

In a meta-analysis of 19 randomized controlled trials involving 7,835 patients with rheumatoid arthritis, abatacept was found to significantly increase the likelihood of achieving an ACR70 response compared to tocilizumab, with a relative risk of 2.217.

Rituximab did not show a significant difference in achieving ACR70 response compared to abatacept, indicating that while all three treatments are options for refractory RA, abatacept may offer superior efficacy over tocilizumab under similar study conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis. Pugliesi, A., de Oliveira, AB., Oliveira, AB., et al.[2023]

A total of 604,157 adverse events (AEs) were reported for COVID-19 vaccines, with the Pfizer-BioNTech and Moderna vaccines accounting for the majority of reports, indicating a need for ongoing safety monitoring.

While most reported AEs were mild, serious outcomes like hospitalization and life-threatening events were noted, particularly among older adults with pre-existing conditions, highlighting the importance of careful surveillance of vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and Comparison of Adverse Events of Coronavirus Disease 2019 Vaccines Reported to the United States Vaccine Adverse Event Reporting System Between 14 December 2020 and 8 October 2021. Zou, C., Xue, X., Qian, J.[2022]

Out of 239.97 million COVID-19 vaccine doses administered, only 141,208 individuals (0.04% to 0.35% depending on the vaccine) reported adverse events, indicating a generally low incidence of side effects across Pfizer-BioNTech, Moderna, and Johnson & Johnson's vaccines.

Most reported side effects were mild and self-limiting, with serious adverse events like anaphylaxis (0.0003%) and death (0.002%) being extremely rare, suggesting a wide safety profile for these vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety profile of COVID-19 vaccinations in the United States. Singh, A., Khillan, R., Mishra, Y., et al.[2021]

As of April 30, 2021, out of 3,586,814 COVID-19 vaccine doses administered in Korea, 16,196 adverse events were reported, with 96.7% classified as non-serious, indicating a high safety profile for the vaccines.

Among the reported serious adverse events, including 73 deaths, none were found to be related to the vaccines, reinforcing the conclusion that the vaccines are safe for the population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COVID-19 vaccine safety monitoring in the Republic of Korea: February 26, 2021 to April 30, 2021. Oh, HK., Kim, EK., Hwang, I., et al.[2021]

In Kansas, only 0.00068% of COVID-19 vaccine doses were associated with adverse events (AERs), indicating a very low incidence of reported reactions among the 2,120,350 doses administered.

The most common AERs included fatigue, tingling, fever, hives, and muscle/joint pain, with no unexpected events reported, and no causal relationship established between vaccination and death, supporting the vaccines' safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The COVID-19 Vaccines: A Description of Adverse Events of Reactions Reported in Kansas. Mills, K., Tri, A., Nilsen, K.[2022]

The COVID-19 vaccines authorized in the U.S. include mRNA vaccines from Pfizer and Moderna, which are 95% effective, and an adenovirus vector-based vaccine from Johnson & Johnson, which is 66% effective against moderate and symptomatic COVID-19.

Safety data from large clinical trials and the general population indicate that these vaccines are safe, highlighting the importance of ongoing research as new variants emerge and vaccines are tested in different age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. Patel, R., Kaki, M., Potluri, VS., et al.[2023]

COVID-19 vaccines have been found to be safe for immunocompromised patients, with recent studies providing reassuring data, particularly for those with HIV infection, despite their exclusion from initial phase 3 trials.

Health organizations, including the CDC, recommend COVID-19 vaccination for immunocompromised individuals, emphasizing that the benefits of vaccination outweigh potential risks, and highlighting the need for education to reduce vaccine hesitancy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommendations. Duly, K., Farraye, FA., Bhat, S.[2022]

Patients with autoimmune diseases and those on immunosuppressive therapies are prioritized for COVID-19 vaccination, but there is a lack of confirmed data on vaccine efficacy in these populations due to their exclusion from clinical trials.

Current COVID-19 vaccines do not use live-attenuated viruses, making them safer for patients with compromised immune systems, and vaccination timing should be tailored to individual patient conditions and treatments to optimize efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Administration of COVID-19 vaccines in immunocompromised patients. Negahdaripour, M., Shafiekhani, M., Moezzi, SMI., et al.[2022]

Only about 25% of lung transplant recipients developed a positive antibody response after receiving two doses of either the Pfizer-BioNTech or Moderna COVID-19 vaccines, indicating a significantly reduced immunogenic response compared to non-transplanted individuals.

The Moderna vaccine showed a trend towards better antibody response in lung transplant recipients compared to the Pfizer vaccine, but overall, the immune response was much lower than that seen in healthy individuals, suggesting the need for further research on optimizing vaccine strategies for this vulnerable group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines. Narasimhan, M., Mahimainathan, L., Clark, AE., et al.[2021]

In a study of 328 subjects, including 131 immunocompromised individuals, it was found that these patients generally had a poor immune response to the SARS-CoV-2 mRNA vaccines, but a booster dose significantly improved their immune response, except for those receiving anti-CD20 antibody treatment.

Immunocompromised individuals who had previously been infected with SARS-CoV-2 and then vaccinated showed a stronger immune response compared to those who were vaccinated without prior infection, highlighting the importance of previous exposure in enhancing vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients. Azzolini, E., Pozzi, C., Germagnoli, L., et al.[2022]

In a study involving 412 immunocompromised patients, the mRNA-1273 vaccine showed a similar antibody response to the BNT162b2 vaccine, confirming its noninferiority in effectiveness against SARS-CoV-2.

While 100% of people living with HIV (PLWH) developed an antibody response, only 60.6% of solid organ transplant recipients (SOTR) did, highlighting a significant difference in vaccine response between these two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial. Speich, B., Chammartin, F., Abela, IA., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Efficacy and safety profile of intravenous tocilizumab versus intravenous abatacept in treating female Saudi Arabian patients with active moderate-to-severe rheumatoid arthritis. [2020]

2. England pubmed.ncbi.nlm.nih.gov

The trajectory of clinical responses in patients with early rheumatoid arthritis who achieve sustained remission in response to abatacept: subanalysis of AVERT-2, a randomized phase IIIb study. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of biologics for the management of rheumatoid arthritis: systematic review and network meta-analysis. [2021]

4. France pubmed.ncbi.nlm.nih.gov

Targeting lymphocyte activation to treat rheumatoid arthritis. [2020]

5. England pubmed.ncbi.nlm.nih.gov

Compared efficacy of rituximab, abatacept, and tocilizumab in patients with rheumatoid arthritis refractory to methotrexate or TNF inhibitors agents: a systematic review and network meta-analysis. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Characteristics and Comparison of Adverse Events of Coronavirus Disease 2019 Vaccines Reported to the United States Vaccine Adverse Event Reporting System Between 14 December 2020 and 8 October 2021. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

The safety profile of COVID-19 vaccinations in the United States. [2021]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

COVID-19 vaccine safety monitoring in the Republic of Korea: February 26, 2021 to April 30, 2021. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

The COVID-19 Vaccines: A Description of Adverse Events of Reactions Reported in Kansas. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

A comprehensive review of SARS-CoV-2 vaccines: Pfizer, Moderna & Johnson & Johnson. [2023]

11. England pubmed.ncbi.nlm.nih.gov

COVID-19 vaccine use in immunocompromised patients: A commentary on evidence and recommendations. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Administration of COVID-19 vaccines in immunocompromised patients. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines. [2021]

14. United States pubmed.ncbi.nlm.nih.gov

mRNA COVID-19 vaccine booster fosters B- and T-cell responses in immunocompromised patients. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

Antibody Response in Immunocompromised Patients After the Administration of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine BNT162b2 or mRNA-1273: A Randomized Controlled Trial. [2022]