Immunogenicity and Safety PCV-20 of the Vaccine Administered During an Acute Febrile Illness in Adults

NCT ID: NCT06822907

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 1052 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-01-31
• Study Completion Date: 2028-10-01

Brief Summary

Streptococcus pneumoniae is responsible for serious infections associated to numerous hospitalizations and high rate of mortality. The incidence and therefore the burden of pneumococcal infections have been significantly reduced thanks to the use of pneumococcal conjugate vaccines (PCVs). PCVs were shown to be effective against vaccine-type serotypes causing both non-invasive and invasive pneumococcal diseases (IPD) in children and adults. PCVs use in children was shown to have an impact on IPD incidence among adults due to herd immunity and on antimicrobial resistance. To increase the protection of at-risk patients against IPD, the 20-valent PCV (PCV-20) is recently recommended in adults, after a period where PCV-13 followed by pneumococcal polysaccharide vaccine 23 valent (PPV-23) was recommended. PCV-20 effectiveness against IPD and against pneumonia was inferred from immunobridging with PCV-13. Indeed PCV-13 was shown effective to reduce the incidence of low respiratory tract infections and IPD (bacteraemia and meningitis) in 65-years-old-adults and older. Currently immunization against S. pneumoniae is recommended with PCV-20 for adult patients at-risk for IPD such as immunocompromised (=high-risk patients) and in immunocompetent people with underlying chronic conditions (cardiovascular, liver, pulmonary, kidney diseases and diabetes mellitus) (=medium risk patients). However, vaccine coverage against IPD in adults remains low globally, and does not exceed 5 % in France. Reducing missed opportunities of vaccination for S. pneumoniae is crucial.

Detailed Description

Patients at-risk of IPD are very frequently hospitalized for acute febrile illnesses. More than 50 % of the IPD at-risk patients hospitalized for an IPD or a pneumonia have been admitted to the hospital during the past 5 years without receiving a pneumococcal vaccination. Hospitalization appears to be therefore an opportunity to provide vaccines. However, physicians usually consider that vaccines should be postponed during an acute febrile illness including if non-severe. This consideration of not vaccinating during an acute febrile illness is however not evidence-based. This is associated to concerns about a potential risk of an impaired response to the vaccine and safety. In children, data about vaccination during a febrile illness have shown no safety nor efficacy concerns. In most countries, recommendations regarding this particular point are unclear.

In fine, vaccination is then rarely provided during the hospital stay as well as after discharge including in the USA, a country where it is recommended to vaccinate whatever the body temperature is and during hospitalization. Reluctance to immunize adults in this situation is probably due to the absence of evidence showing that it is as effective and safe as vaccinating patients without an acute or febrile illness.

To reduce the number of missed opportunities to immunize adults against S. pneumoniae, investigators aim to demonstrate that the administration of PCV-20 during an acute non-severe febrile illness is non-inferior than the administration one month after fever resolution in terms of immunogenicity (assessed by vaccine types (VT) Immunoglobulin G (IgG) concentrations and at least 2-fold change increase), and that it is as safe.

Conditions

Acute Febrile Illness; Pneumococcal Infections

Keywords

vaccin; pneumococcal; Prevenar 20; Acute febrile illness; infections; PCV-20; PCV-21

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

Early vaccination

The patient will receive unique dose of the PCV-20 vaccine as soon as possible and until 72h after apyrexia.

The "Prevenar 20" will be used

Group Type: EXPERIMENTAL

Early intervention

Intervention Type: BIOLOGICAL

In this arm, patient will receive unique dose of the PCV-20 vaccine (Prevnar 20) as soon as possible and until 72h after apyrexia.

The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.

Delayed vaccination

From 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature \< 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive PCV-20 vaccination The "Prevenar 20" will be used

Group Type: ACTIVE_COMPARATOR

Delayed intervention

Intervention Type: BIOLOGICAL

In this arm, from 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature < 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive unique dose of the PCV-20 vaccine (Prevnar 20).

The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.

Interventions

Early intervention

In this arm, patient will receive unique dose of the PCV-20 vaccine (Prevnar 20) as soon as possible and until 72h after apyrexia.

The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.

Intervention Type: BIOLOGICAL

Delayed intervention

In this arm, from 15 days and until 58 days after fever resolution (i.e after the first day with a body temperature < 37.5°C without paracetamol use in the 6 previous hours) (whether or not the patient has been discharged) in the absence of fever, the patient will receive unique dose of the PCV-20 vaccine (Prevnar 20).

The "Prevenar 20" will be used Prevenar 20 will be injected by intramuscular route. The preferred site of injection is the deltoid muscle of the upper arm in adults.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• History of body temperature ≥ 38°C measured at least twice prior to randomization (Randomization must be performed as soon as possible on a febrile patient or 72 hours after apyrexia at the latest)
• Having at least one comorbidity that defines patients as medium or high risk for pneumococcal invasive infection:

• Medium risk: Cyanogenic congenital heart disease; chronic heart failure; chronic respiratory failure; chronic obstructive pulmonary disease; emphysema; severe asthma under chronic treatment; chronic renal failure; chronic liver disease; diabetes mellitus treated; Osteo-meningeal leak or cochlear implant; Age > 65 years old.
• High risk : Hypo or asplenic people; hereditary immunodeficiency syndromes; people living with HIV; solid organ transplanted; People under immunosuppressors (corticosteroids, biotherapy) for an auto-immune or an inflammatory chronic disease; patients with nephrotic syndrome
• Hospitalization for > 24 hours long
• Social security affiliation
• Signed informed consent

Exclusion Criteria

• Patient unable to give informed consent
• Curators, wardship
• History of previous vaccination with PCV-7 or PCV-13 or PCV-20
• History of PPV-23 in the previous year
• Patient having received another vaccination within one month prior to inclusion or planning another vaccination in the month after inclusion except for Influenza vaccine.
• Patient with history of bone marrow transplantation
• Patient with haematological malignancies
• Patient under chemotherapy for solid tumor or with a history of chemotherapy in the past three months
• Patient treated with Rituximab currently or in the past 6 months
• Patient with Sequential Organ Failure Assessment (qSOFA ) score ≥ 2 at randomization (acute severe febrile illness)
• Patient hospitalized in an Intensive Care Unit
• Pregnancy
• Breastfeeding woman
• Recipients of polyclonal gammaglobulins in the past three months
• Inability to follow the protocol
• Bleeding disorder contra-indicating intramuscular injection according to the investigator
• History of allergy to PCV-20 or vaccine-related components.
• S. pneumoniae infection with laboratory confirmation (blood culture, culture from a sterile site, urinary or Cerebrospinal fluid antigens, sputum culture with > 10^7 colony forming unit (CFU)/mL) being the cause of the current hospitalization

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health, France

OTHER_GOV

Sponsor Role: collaborator

IREIVAC/COVIREIVAC Network

UNKNOWN

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Elisabeth BOTELHO-NEVERS, MD PhD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

CHU de Saint-Etienne

Saint-Etienne, France, France

Centre Hospitalier

Annecy, , France

Centre Hospitalier Universitaire

Besançon, , France

Centre Hospitalier

Bordeaux, , France

Centre Hospitalier Universitaire

Brest, , France

Centre Hospitalier

Brest, , France

Centre Hospitalier General Metropole Savoie

Chambéry, , France

Centre Hospitalier de Creteil

Créteil, , France

Centre Hospitalier Universitaire

Dijon, , France

Centre Hospitalier Universitaire

Grenoble, , France

Centre Hospitalier

La Roche-sur-Yon, , France

Centre Hospitalier General

Le Mans, , France

Centre Hospitalier

Le Puy-en-Velay, , France

Centre Hospitalier Universitaire

Lille, , France

Hospices Civils de Lyon

Lyon, , France

Centre Hospitalier Regional Universitaire

Montpellier, , France

Centre Hospitalier Universitaire

Nancy, , France

Centre Hospitalier Universitaire

Nantes, , France

Centre Hospitalier Universitaire

Nice, , France

Centre Hospitalier Universitaire

Nîmes, , France

Centre Hospitalier Bichat

Paris, , France

Assistance Publique Hopitaux de Paris

Paris, , France

Centre Hospitalier Universitaire

Rennes, , France

Centre Hospitalier Universitaire

Rouen, , France

Countries

France

Central Contacts

Elisabeth BOTELHO-NEVERS, MD PhD

Role: CONTACT

Phone: (0)477829234

Email: Elisabeth.Botelho-Nevers@chu-st-etienne.fr

Facility Contacts

JANSSEN CECILE, MD

Role: primary

KEVIN BOUILLER, MD

Role: primary

CHARLES CAZANAVE, PHD

Role: primary

ROZENN LE BERRE, PHD

Role: primary

SYLVAIN JAFFUEL, MD

Role: primary

EMMANUEL FORESTIER, MD

Role: primary

ANTOINE FROISSART, MD

Role: primary

LIONEL PIROTH, PHD

Role: primary

OLIVIER EPAULARD, PHD

Role: primary

THOMAS GUIMARD, MD

Role: primary

SOPHIE BLANCHI, MD

Role: primary

CYRILLE CORNILLE, MD

Role: primary

KARINE FAURE, PHD

Role: primary

ANNE CONRAD, MD

Role: primary

CORRINE MERLE DE BOEVER, MD

Role: primary

BENJAMIN LEFEVRE, PHD

Role: primary

ANNE-SOPHIE LECOMPTE, MD

Role: primary

ELISA DEMONCHY, MD

Role: primary

PAUL LOUBET, PHD

Role: primary

XAVIER LESCURE, PHD

Role: primary

ODILE LAUNAY, PHD

Role: primary

LEA PICARD, MD

Role: primary

MANUEL ETIENNE, PHD

Role: primary

Other Identifiers

2024-517411-73-00

Identifier Type: CTIS

Identifier Source: secondary_id

19PH225

Identifier Type: -

Identifier Source: org_study_id