Immunogenicity and safety of the 20-Valent pneumococcal conjugate vaccine (PCV-20) administered during an acute febrile illness in adults

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Saint Etienne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2025-02-24

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Ministère de la Santé

External identifiers

EU CT number

2024-517411-73-00

ClinicalTrials.gov

NCT06822907

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate that the immune response at one month after 20-valent pneumococcal conjugate vaccine (PCV-20) administered during an acute febrile illness is non-inferior to the immune response obtained at one month after PCV-20 administered 15-58 days after resolution of the acute febrile illness in unvaccinated patients at high and medium risk for pneumococcal infections.

Secondary objectives 11

1. To compare at one month after vaccination the safety of the administration of PCV-20 during an acute febrile illness or 15-58 days after the acute febrile illness resolution.
2. To evaluate the impact of PCV-20 injection during an acute febrile illness on seroconversion in PCV-20 serotypes (serotype/serotype)
3. To compare functional immune response by opsonophagocytic activity (OPA) one month after the administration of PCV-20 either during an acute febrile illness or 15-58 days after the acute febrile illness resolution.
4. To compare the immune response one year after the administration of PCV-20 either during an acute febrile illness or 15-58 days after the acute febrile illness resolution.
5. To evaluate the incidence of low respiratory tract infections one year after vaccination in both arms (PCV-20 vaccination during an acute febrile illness versus 15-58 days after the acute febrile illness resolution).
6. To evaluate the incidence of laboratory confirmed Streptococcus pneumoniae infections until one year after inclusion (PCV-20 vaccination during an acute febrile illness versus 15-58 days after the acute febrile illness resolution).
7. To evaluate the impact of the gut microbiota on the immune response in both arms (during an acute febrile illness or 15-58 days after resolution of the acute febrile illness)
8. To evaluate the reactogenic inflammatory response after vaccination in both arms (during an acute febrile illness or 15-58 days after resolution of the acute febrile illness) (Only for CHU of St Etienne)
9. To compare cellular immune response at one month after PCV-20 administration either during an acute febrile illness or 15-58 days after resolution of the acute febrile illness ) (Only for CHU of St Etienne)
10. To compare cellular immune response at one year after PCV-20 administration either during an acute febrile illness or 15-58 days after resolution of the acute febrile illness. ) (Only for CHU of St Etienne)
11. To compare salivary IgA level at one month after PCV-20 administration either during a febrile illness or 15-58 days after resolution of the acute febrile illness.

Conditions and MedDRA coding

Patient with medium or high risk for pneumococcal invasive infection

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age ≥18 and <85 years-old
2. 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)
3. 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 cardiopathy; 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 ;65 years old and more 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
4. Scheduled hospitalization for > 24 hours long
5. Social security affiliation
6. Signed informed consent

Exclusion criteria 19

1. Patient unable to give informed consent
2. Patient with qSOFA score ≥ 2 at randomization (acute severe febrile illness)
3. Patient hospitalized in an Intensive Care Unit
4. Pregnancy
5. Breastfeeding woman
6. Recipients of polyclonal gammaglobulins in the past three months
7. Inability to follow the protocol
8. Bleeding disorder contra-indicating intramuscular injection according to the investigator
9. History of allergy to PCV-20 or vaccine-related components.
10. S. pneumoniae infection with laboratory confirmation (blood culture, culture from a sterile site, urinary or Cerebrospinal fluid antigens, sputum culture with > 10^7 CFU/mL), if available and if the result is known before randomization.
11. Curatorship, wardship
12. History of previous vaccination with PCV-7 or PCV-13 or PCV-20
13. History of PPV-23 in the previous year
14. Patient having received another vaccination within one month prior to inclusion or planning another vaccination in the month after inclusion except for Influenza and and mRNA COVID-19 vaccines.
15. Patient with history of bone marrow transplantation
16. Patient with haemotological malignancies
17. Patient under chemotherapy for solid tumor or with a history of chemotherapy in the past three months
18. Patient treated with Rituximab currently or in the past 6 months
19. Impossibility of providing comprehensible information to the patient

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Proportion of immune “good responders” to PCV-20 at 1 month after vaccination in both arms. Immune“Good responders” are defined by both of the following criteria : a seroconversion (a 2-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA,AND an immune protective response defined as ELISA IgG > 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.
2. OR a seroconversion (a 4-fold increase in VT IgG after vaccination), for ≥10 vaccine serotypes (VT) among the 13 tested on 20 in ELISA, AND an immune protective response defined as ELISA IgG < 1,3 μg/mL in ≥ 10 out 13 VT tested in both arms in the month following vaccination.

Secondary endpoints 11

1. Safety endpoints in both arms in the month following vaccination: Number, type and severity of adverse events Frequency of local reactions Frequency of systemic events related to the vaccination
2. Proportion of immune good responders serotype by serotype at one month post vaccination (ELISA 2-fold increase and ELISA IgG > 1,3μg/mL).
3. OPA IgG titers for serotype by serotype at one month post vaccination in both groups measured a posteriori among immune good responders
4. Proportion of the participants immune “good responders” to PCV-20 in both arms, at 1 year after vaccination. “Good responders” being defined above (primary end-point)
5. Number of low respiratory tract infections events in both arms until one year after vaccination.
6. Number of confirmed S.pneumoniae infections in both arms until one year after inclusion
7. Description of richness and diversity of gut microbioma before vaccination associated with people qualified as immune good responders in both arms
8. Fold change kinetics (transcriptomics) (before and at 24 hours after vaccination) of vaccine-induced gene signatures in peripheral blood mononuclear cells and serum cytokine levels at baseline and 24 hours after vaccination in both arms.
9. Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells in both arms at one month post vaccination (Only for CHU of St Etienne)
10. Frequency of specific PCV-20 IFNg secreting CD4 or CD8 T cells in both arms at one year post vaccination (Only for CHU of St Etienne)
11. Proportion of volunteers with salivary IgA (specific of pneumococcus) in both arms at one month post vaccination

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Saint Etienne

Sponsor organisation

Centre Hospitalier Universitaire De Saint Etienne

Address

Avenue Albert Raimond

City

Saint Priest En Jarez

Postcode

42270

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Pr. Elisabeth BOTELHO-NEVERS

Public contact point

Organisation

Centre Hospitalier Universitaire De Saint Etienne

Contact name

Pr. Elisabeth BOTELHO-NEVERS

Locations

1 EU/EEA country · 24 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications