NCT05409612

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

Multicenter, Randomized, Open, Phase III, Trial Assessing the Immunogenicity and Safety of Two Influenza Vaccine Strategies Among Severe Obese Adult Patients

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 206 (actual)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Obese adults are at higher risk of complications and mortality due to influenza infections than healthy adults. The few studies available showed lower vaccine response in obese patients compared to healthy adults and moderate efficacy of standard influenza vaccines among these subjects. Data from the population \> 50 years show that a recombinant high dose quadrivalent vaccination strategy improve immunological and clinical efficacy against influenza with comparable rates of local and general solicited reactions. Investigators hypothesize that 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. The primary objective is to assess if the immune response of the new quadrivalent recombinant high-dose influenza vaccine (RIV4) is superior to the current quadrivalent standard dose influenza vaccine (SD) in adult patients with severe obesity in terms of geometric mean titers (GMTs) for each strain at 1 month. The primary endpoint: Ratio (RIV4/SD) of GMTs of each of the 4 strains at 1-month post-vaccination. The ratio of GMTs will be computed by taking the antilog of the difference between means of log-transformed titers. It is a Randomized, open, multicenter, trial in France, evaluating the immunological response and safety of two influenza vaccine strategies using a standard quadrivalent vaccine (Vaxigriptetra®) and the new high-dose recombinant quadrivalent vaccine (Supemtek®). The single administration of influenza vaccine will be performed at D0: Vaxigriptetra® or Supemtek® according to randomization allocation. Three follow-up visits will be performed at M1 and M6 during consultations in the clinical units where participants are usually followed. This multicenter research will involve the participation of the 10 centers in France (metropolitan France and French overseas departments and territories). Each hospital involves a single participating department. All investigational sites belong to the FORCE (national network of clinical research specializing in the study of obesity and associated metabolic diseases) or to the I-REIVAC (Innovative Clinical Research Network In Vaccinology). The duration of recruitment will be 5 months. The duration of participation for each participant will be 6 months, the total duration of the study will be 11 months. For this study, 206 patients will be recruited.

Conditions

• Morbid Obesity
• Severe Obesity

Interventions

Type	Name	Description
BIOLOGICAL	Supemtek®	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	Vaxigriptetra®	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.

Timeline

• Start date: 2022-11-07
• Primary completion: 2023-04-20
• Completion: 2023-10-03
• First posted: 2022-06-08
• Last updated: 2024-02-26

Locations

1 site across 1 country: France