The Immunogenicity and Safety of COVID-19 and Influenza Vaccine Co-administration and Interval in Immunocompromised Hosts

Plain English Summary

COVID-19 Booster and IIV Schedule in Immunocompromised Hosts is a Phase 2 clinical trial sponsored by McGill University Health Centre/Research Institute of the McGill University Health Centre studying COVID 19, Influenza, Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus, Inflammatory Bowel Disease, Solid Organ Transplant Recipients, Immunocompromised Host, People Living With HIV. This study tests different schedules for giving the COVID-19 booster and flu shots to people with weakened immune systems. It is for adults who have a condition that makes them immunocompromised, such as those who have had an organ transplant, have HIV, inflammatory bowel disease, or autoimmune conditions like rheumatoid arthritis or lupus. Participants will receive either the COVID-19 booster and flu shot at the same time or one month apart, and will get booster shots either 3 or 6 months later. The main alternative is to follow standard vaccination guidelines without participating in this specific trial. The trial aims to enroll 660 participants.

Official 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

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older who have had at least three doses of a COVID-19 vaccine. Individuals with specific immunocompromising conditions like organ transplant recipients (at least 3 months post-transplant), people with HIV meeting certain criteria, or those with inflammatory bowel disease, rheumatoid arthritis, or lupus treated with immune-suppressing medications. People who have not received an influenza vaccine in the last 6 months or a COVID-19 booster in the last 3 months. Individuals with a history of severe reactions to these vaccines, certain neurological conditions after vaccination, bleeding disorders, primary immune deficiencies, or those who have recently received chemotherapy or intravenous immunoglobulin. This trial is studying COVID 19, Influenza, Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus, Inflammatory Bowel Disease, Solid Organ Transplant Recipients, Immunocompromised Host, People Living With HIV, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how well the body's immune system responds to the vaccines, indicating the level of protection against COVID-19 and influenza, which helps determine the best vaccination s The specific primary outcome measures are: Median neutralization capacity against prevalent SARS-CoV-2 variant (At 1-month and 2-months following the initial COVID-19 booster dose for primary objective 1 and at 12-months and 6-months following initial COVID-19 booster dose for primary objective 2). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it aims to find the most effective way to protect vulnerable individuals with weakened immune systems from both COVID-19 and influenza, addressing a gap in understandin Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets COVID 19, Influenza, Rheumatoid Arthritis (RA), Systemic Lupus Erthematosus, Inflammatory Bowel Disease, Solid Organ Transplant Recipients, Immunocompromised Host, People Living With HIV, where improved treatment options are needed.

Investor Insight

This trial signals a focus on improving vaccine efficacy in a significant patient population, potentially leading to better public health strategies and a stronger market for specialized vaccine formu Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval. The large enrollment target of 660 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for your specific health condition and current medications. Understand that you will receive different combinations and timings of COVID-19 booster and flu shots. You will need to provide blood samples to check your immune response and will be monitored for any side effects or changes in your health. This trial is currently recruiting participants. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: FACTORIAL
• Masking: NONE
• Enrollment: 660 participants

Interventions

• BIOLOGICAL: Inactivated influenza vaccine (IIV) at baseline — National Advisory Committee on Immunization (NACI) recommended seasonal inactivated influenza vaccine for moderate to severely immunocompromised patients by age at baseline
• BIOLOGICAL: COVID-19 Vaccines at a 3-month interval — Updated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 3-month interval
• BIOLOGICAL: Inactivated influenza vaccine at Month 1 — National Advisory Committee on Immunization (NACI) recommended seasonal inactivated influenza vaccine for moderate to severely immunocompromised patients by age 1-month following initial COVID-19 booster
• BIOLOGICAL: COVID-19 Vaccines at a 6-month interval — Updated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 6-month interval

Primary Outcomes

• Median neutralization capacity against prevalent SARS-CoV-2 variant (At 1-month and 2-months following the initial COVID-19 booster dose for primary objective 1 and at 12-months and 6-months following initial COVID-19 booster dose for primary objective 2)

Secondary Outcomes

• Median neutralization capacity against ancestral and SARS-CoV-2 variant in vaccine (For primary objective 1, at 1-month and 2-months after the COVID-19 booster. For primary objective 2, at 6 and 12 months)
• Anti-Spike and anti-Nucleocapsid concentrations (Baseline, 1, 2, 4, 6, 7, 10, and 12 months after the first study COVID-19 booster)
• IgA, and IgM antibody concentration (Baseline, 1, 2, 4, 6, 7, 10, and 12 months after the first study COVID-19 booster)
• Hemagglutination inhibition (HI) response (1 month after IIV)
• T-cell responses to SARS-CoV-2 and cytokines assays (Baseline, 1, 2, 4, 6, 7, 10, and 12 months after the first study COVID-19 booster)

Full Eligibility Criteria

Inclusion Criteria:

\- All participants must meet ALL the following inclusion criteria: i. Adults (≥18 years) ii. Received the primary mRNA COVID-19 vaccine series (i.e., ≥3 doses) iii. 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 following conditions: i) AIDS-defining illness in the last 6 months, ii) TB diagnosis in the last 6-months, iii) CD4\<200 cells/µL in the last 6 months, iv) CD4%\<15% in the last 6 months, or v) absence of HIV viral suppression in the last 6 months; 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.

Exclusion Criteria:

* Potential participants who meet ANY of the following criteria will be excluded:

  i. Received any of the following:
  1. Annual vaccination against influenza \< 6 months ago
  2. COVID-19 booster \< 3 months ago ii. History of any of the following:

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  1. life-threatening reaction any component of the IIV or COVID-19 vaccines
  2. Guillain-Barre syndrome or myocarditis within 6 weeks of a previous influenza or COVID-19 vaccination
  3. Contraindication to intramuscular vaccines such as bleeding disorder, severe thrombocytopenia, etc; iii. Receiving intravenous immunoglobulins; iv. Have underlying primary inborn errors of immunity; v. Receiving chemotherapy such as cyclophosphamide \&lt; 6-months ago; vi. Unable to provide informed consent

Trial Locations

• Maisonneuve -Rosemont Installation, Montreal, Quebec, Canada
• Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Quebec, Canada
• Research Institute of McGill University Health Centre, Montreal, Quebec, Canada

Frequently Asked Questions

Related Conditions

• COVID-19
• Influenza
• Rheumatoid Arthritis
• Systemic Lupus Erythematosus
• Inflammatory Bowel Disease
• Crohn's Disease
• Ulcerative Colitis
• Solid Organ Transplantation
• HIV/AIDS
• Immunocompromised Host

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