COVID-19 Booster and IIV Schedule in Immunocompromised Hosts

NCT06599658 | Recruiting Phase 2 DMC

• 1 other identifier: 2025-10781
• Study Type: interventional
• Target: 660
• Locations: 1 country
• Sites: 3

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. 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. 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?

Conditions

Rheumatoid Arthritis (RA); Systemic Lupus Erthematosus; Inflammatory Bowel Disease; Solid Organ Transplant Recipients; Immunocompromised Host; People Living With HIV; COVID 19; Influenza

Keywords

Vaccine; Immunogenicity; Safety

Outcome Measures

Primary Outcomes (1)

• Median neutralization capacity against prevalent SARS-CoV-2 variant

  Median neutralization capacity of patient sera/plasma from each group, as measured by half maximal inhibitory dilution (ID50) against the prevalent SARS-CoV-2 variant circulating at time of measurement. For objective 1, this outcome will be compared between the co- vs. sequential administration arms at 1-month (T1) after the COVID-19 booster (peak humoral response). This outcome will also be compared at 2-months (T2). For objective 2, this outcome will be compared 12-months (T12) after the first COVID-19 booster between participants who have received COVID-19 boosters at 0, 3, 6 and 9 months (3-month interval arm) vs. those who received COVID-19 booster doses at 0 and 6-months (6-month interval arm). This outcome will also be compared at 6-months (T6).

  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 (6)

• 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

Other Outcomes (7)

• Adverse reactions to the vaccines

  Following COVID-19 booster and/or IIV at baseline, 1, 3, 6 and 9-months

• Evidence of immune activation

  Quarterly (at baseline, 3, 6, 9, and 12-months)

• SARS-CoV-2 infections

  Every visit (at baseline, 1, 2, 3, 4, 6, 7, 9, 10, and 12-months)

Study Arms (4)

Group 1

EXPERIMENTAL

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

Biological: Inactivated influenza vaccine (IIV) at baseline; Biological: COVID-19 Vaccines at a 3-month interval

Group 2

EXPERIMENTAL

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

Biological: COVID-19 Vaccines at a 3-month interval; Biological: Inactivated influenza vaccine at Month 1

Group 3

EXPERIMENTAL

Covid-19 booster every 6 months and IIV at baseline

Biological: Inactivated influenza vaccine (IIV) at baseline; Biological: COVID-19 Vaccines at a 6-month interval

Group 4

EXPERIMENTAL

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

Biological: Inactivated influenza vaccine at Month 1; Biological: COVID-19 Vaccines at a 6-month interval

Interventions

Inactivated influenza vaccine (IIV) at baseline BIOLOGICAL

National Advisory Committee on Immunization (NACI) recommended seasonal inactivated influenza vaccine for moderate to severely immunocompromised patients by age at baseline

Group 1; Group 3

COVID-19 Vaccines at a 3-month interval BIOLOGICAL

Updated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 3-month interval

Group 1; Group 2

Inactivated influenza vaccine at Month 1 BIOLOGICAL

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

Group 2; Group 4

COVID-19 Vaccines at a 6-month interval BIOLOGICAL

Updated NACI recommended COVID-19 booster for moderate to severely immunocompromised patients at a 6-month interval

Group 3; Group 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Potential participants who meet ANY of the following criteria will be excluded:
• i. Received any of the following:
• Annual vaccination against influenza \< 6 months ago
• COVID-19 booster \< 3 months ago ii. History of any of the following:
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• life-threatening reaction any component of the IIV or COVID-19 vaccines
• Guillain-Barre syndrome or myocarditis within 6 weeks of a previous influenza or COVID-19 vaccination
• 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

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Centre hospitalier de l'Université de Montréal (CHUM): collaborator

Study Sites (3)

Maisonneuve -Rosemont Installation

Montreal, Quebec, H1T2M4, Canada

RECRUITING

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C1, Canada

RECRUITING

Research Institute of McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

MeSH Terms

Conditions

COVID-19; Influenza, Human; Arthritis, Rheumatoid; Inflammatory Bowel Diseases

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Orthomyxoviridae Infections; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Central Study Contacts

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

CONTACT

5149341934; ruth.sapir-pichhadze.med@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 11, 2024
• First Posted: September 19, 2024
• Study Start: November 20, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 10, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (3)