Trial Assessing the Immunogenicity and Safety of Two Influenza Vaccine Strategies Among Severe Obese Adult Patients

NCT05409612 | Completed Phase 3

• 2 other identifiers: APHP2000392021-002691-39
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity has been considered as a risk factor for mortality and development of complications during infection with the influenza virus. Several case studies of severe and fatal infections have identified possible effects of obesity on disease progression; these effects include extensive viral replication in the deep lung, progression to viral pneumonia, and prolonged and increased viral shedding. These points may be linked to obesity which causes a chronic state of meta-inflammation with systemic implications for immunity: obese patients exhibit delayed and blunted innate and adaptive immune responses to influenza virus infection, and they experience poor recovery from the disease leading to an increased susceptibility to secondary bacterial infections and poor healing of the lung epithelium. Furthermore, in obese people, influenza virus may exploit the lack of antiviral pressure, generate a more virulent population and increase disease severity Due to the growing prevalence of obesity worldwide (500 million subjects in 2017), it is important to be able to offer vaccines that provide the highest protection for this at-risk population. The quadrivalent recombinant high-dose influenza vaccine has been shown to have greater immunogenicity and efficacy than standard influenza vaccine in non-obese adults older than 50 years. However, this vaccine has never been evaluated in obese subjects. Investigators thus planned this trial to assess whether the use of the new quadrivalent recombinant high-dose influenza vaccine (RIV4) will induce a better immunological answer than current quadrivalent standard vaccine (SD) in patients with severe obesity, with an acceptable safety profile, thus leading to a better protection against influenza in this population at high risk of influenza complications.

Conditions

Morbid Obesity; Severe Obesity

Keywords

Obesity; influenza vaccine; immunological response; RIV4

Outcome Measures

Primary Outcomes (1)

• Ratio (RIV4/SD) of geometric mean titers (GMTs) of each of the 4 strains at 1-month post-vaccination.obesity in terms of geometric mean titers (GMTs) for each strain at 1 month.

  The ratio of GMTs will be computed by taking the antilog of the difference between means of log-transformed titers.

  1 month

Secondary Outcomes (18)

• seroconversion rate for each of the 4 strains at 1 month after vaccination

  1 month

• seroconversion rate for each of the 4 strains at 6 month after vaccination

  6 month

• seroconversion factor (or geometric mean fold increase) for each of the 4 strains at 1 month after vaccination.

  1 month

• seroconversion factor (or geometric mean fold increase) for each of the 4 strains at 6 month after vaccination.

  6 month

• seroprotection rate defined as the post-vaccination HI titer ≥1:40 for each of the 4 strains at 1 month after vaccination.

  1 month

Study Arms (2)

Supemtek® arm

ACTIVE COMPARATOR

Patients recieving a quadrivalent recombinant high-dose influenza vaccine containing 45 µg of hemagglutinin (HA) for each of the 4 strains included (2 strains A and 2 strains B). Solution for injection is sterile liquid supplied in 0.5mL single dose pre-filled syringe. Vaccine is injected intra-muscularly in the non-dominant arm at Day 0.

Biological: Supemtek®

Vaxigriptetra® arm

ACTIVE COMPARATOR

Patients receiving a quadrivalent inactivated influenza vaccine containing 15 µg of hemagglutinin (HA) for each of the 4 strains included. Suspension for injection is sterile liquid supplied in 0.5mL single dose pre-filled syringe. Vaccine is injected intra-muscularly in the non-dominant arm at Day 0.

Biological: Vaxigriptetra®

Interventions

Supemtek® BIOLOGICAL

Quadrivalent recombinant high-dose influenza vaccine containing 45 µg of hemagglutinin (HA) for each of the 4 strains included (2 strains A and 2 strains B). Solution for injection is sterile liquid supplied in 0.5mL single dose pre-filled syringe. Vaccine is injected intra-muscularly in the non-dominant arm at Day 0.

Supemtek® arm

Vaxigriptetra® BIOLOGICAL

Quadrivalent inactivated influenza vaccine containing 15 µg of hemagglutinin (HA) for each of the 4 strains included. Suspension for injection is sterile liquid supplied in 0.5mL single dose pre-filled syringe. Vaccine is injected intra-muscularly in the non-dominant arm at Day 0.

Vaxigriptetra® arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 and ≤75 years old
• Body Mass Index (BMI) ≥35 kg/m2
• No previous vaccination against influenza (in the preceding 6 months) with either the trial vaccine or another vaccine
• Absence of health event satisfying the definition of a serious adverse event, or a change in an ongoing drug therapy due to therapeutic failure or symptoms of drug toxicity, within 15 days prior to enrolment.
• Signed informed consent
• Participants covered by social security regimen .

You may not qualify if:

• Known active infection with HIV and / or HBV (HBs antigen) and / or HCV (RNA positive viral load)
• Immunodepression or diagnosis of having congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus, rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory, bowel disease, or other autoimmune condition
• Known acute evolving neurological disorder or history of Guillain-Barré syndrome.
• Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (tympanic temperature ≥38°C on the day of vaccination). A subject should not be included in the trial until the condition has resolved or the febrile event has subsided.
• Proven Influenza infection in the 6 months preceding the study
• Known systemic hypersensitivity to any of the vaccine components, including a documented allergy to egg proteins, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
• Receipt of any vaccine in the 2 weeks (14 days) preceding the trial vaccination
• History of bariatric surgery in the 2 years preceding the study.
• Bariatric surgery planned during the study period.
• Receipt of immune globulins, blood or blood-derived products in the 3 months preceding the study or planned during the study period.
• Taking immunosuppressive treatment (including chemotherapy, oral corticosteroids with doses ≥10 mg/day of prednisone or equivalent during ≥15 days) or radiotherapy in the 6 months preceding the study or planned during the study.
• Contraindication to intramuscular injection
• Female subjects of childbearing potential :
• without an adequate contraception (see chapter 5.8) for 30 days prior to vaccination within the context of the study,
• breastfeeding

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Sanofi Pasteur, a Sanofi Company: collaborator
• Hospices Civils de Lyon: collaborator

Study Sites (1)

Pitie-Salpêtrière hospital APHP

Paris, 75013, France

Location

MeSH Terms

Conditions

Obesity, Morbid; Obesity; Influenza, Human

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Odile LAUNAY, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2022
• First Posted: June 8, 2022
• Study Start: November 7, 2022
• Primary Completion: April 20, 2023
• Study Completion: October 3, 2023
• Last Updated: February 26, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodological sound proposal.

Locations

FR (1)