COVID-19 Booster + Flu Vaccine for Immunocompromised People

(CO2I2 Trial)

Recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods for administering COVID-19 boosters and flu shots to individuals with weakened immune systems. Researchers aim to determine if receiving both vaccines simultaneously is as effective as receiving them sequentially. They are also evaluating whether administering COVID-19 boosters every three months maintains protection better than every six months. The trial seeks participants who have received a solid organ transplant, are living with HIV, or have certain immune-related diseases like inflammatory bowel disease or rheumatoid arthritis. Participants will aid researchers in understanding how to enhance vaccine responses in those with immune-compromising conditions. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant findings.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the COVID-19 booster and the inactivated flu vaccine (IIV) have been tested in various groups, including individuals with weakened immune systems. COVID-19 vaccines, such as those from Moderna, have full FDA approval for people over 18, indicating they have passed strict safety checks. These vaccines are generally well-tolerated, with most side effects being mild, such as soreness at the injection site or mild flu-like symptoms that resolve on their own.

For the IIV, studies have demonstrated its effectiveness in preventing the flu in adults and its general safety, even for those with immune system challenges. Common side effects are mild, like arm soreness or a low-grade fever.

The trial under consideration is a Phase 2 study. This indicates that the treatment has shown some safety in earlier studies and is now being tested in more people to better understand its effects. This phase helps gather more detailed safety information, especially for specific groups like those with weakened immune systems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores the timing and frequency of COVID-19 booster shots alongside the flu vaccine for immunocompromised individuals. Unlike standard treatments that typically involve annual flu vaccinations and COVID-19 boosters as needed, this trial investigates whether more frequent COVID-19 boosters (every 3 or 6 months) can provide enhanced protection. By examining different schedules for administering the inactivated influenza vaccine (IIV), either at baseline or one month later, the trial aims to determine the optimal timing to maximize immune response. This could lead to a more personalized and effective vaccination strategy, offering better protection for those with weakened immune systems.

What evidence suggests that this trial's treatments could be effective for immunocompromised people?

Research has shown that COVID-19 vaccines work well for people with weakened immune systems, being 64% to 90% effective at preventing infection and up to 100% effective at preventing severe illness. The vaccines help the body by producing antibodies that fight the virus. In this trial, participants will receive COVID-19 booster shots at different intervals to assess the effectiveness of maintaining strong protection over time. For the flu vaccine, higher-dose versions are recommended to help people with weakened immune systems respond better. Although the immune response might not be as strong as in the general population, these vaccines are generally safe and can still help protect against the flu. Participants in this trial will receive the flu vaccine at either baseline or one month, depending on their assigned group. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Centre hospitalier de l'Université de Montréal (CHUM)

Collaborator

Trials

389

Recruited

143,000+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

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Comparing the COVID-19 Vaccines: How Are They Different? In December 2020, Pfizer-BioNTech's Phase 3 clinical data for its original vaccine (which is no longer in circulation) showed 95% efficacy for ...

2. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm

Interim Estimates of 2024–2025 COVID-19 Vaccine ... Vaccine effectiveness (VE) of 2024–2025 COVID-19 vaccine was 33% against COVID-19–associated emergency department (ED) or urgent care (UC) visits among adults ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510226

Association of 2024–2025 Covid-19 Vaccine with ... In this study, we used the electronic health care databases of the Department of Veterans Affairs (VA) to evaluate the effectiveness of receipt ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8862165/

COVID-19 vaccine effectiveness among immunocompromised ... S (Janssen), and ChAdOx1 nCoV-19 (Oxford/AstraZeneca), ranged from 64% to 90% against SARS-CoV-2 infection, 73% to 84% against symptomatic illness, 70% to 100% ...

5. mayoclinic.org mayoclinic.org/diseases-conditions/coronavirus/in-depth/different-types-of-covid-19-vaccines/art-20506465

Different types of COVID-19 vaccines: How they work Each COVID-19 vaccine causes the immune system to create proteins called antibodies. These proteins fight infection with the COVID-19 virus.

6. cdc.gov cdc.gov/covid/hcp/vaccine-considerations/overview.html

Overview of COVID-19 Vaccines and Vaccination Learn about types of COVID-19 vaccines and find recommendations, dosage, and overview of schedule.

7. idsociety.org idsociety.org/Seasonal-RTI-Vaccinations-in-Immunocompromised-Patients/

IDSA 2025 Guidelines on the Use of Vaccines ... IDSA 2025 Guidelines on the Use of Vaccines for the Prevention of Seasonal COVID-19, Influenza, and RSV Infections in Immunocompromised Patients.

8. nejm.org nejm.org/doi/full/10.1056/NEJMsa2514268

Updated Evidence for Covid-19, RSV, and Influenza ... Influenza vaccination had a pooled vaccine effectiveness of 48% (95% CI, 39 to 55) in adults between the ages of 18 and 64 years and 67% (95% CI ...

9. pfizer.com pfizer.com/news/articles/understanding_six_types_of_vaccine_technologies

Understanding Six Types of Vaccine Technologies We can potentially go in and change the mRNA in the formulation to target a new antigen and can make a lot of high-quality vaccine material relatively quickly.”.