Pneumococcal polysaccharide serotypes conjugated to CRM197 (20-valent pneumococcal conjugate vaccine) for Acute febrile illness | Increased risk for invasive pneumococcal disease

Inclusion criteria

• {"criterion_text":"- Age ≥18 and <85 years-old\n- 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)\n- 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\n- Scheduled hospitalization for > 24 hours long\n- Social security affiliation\n- Signed informed consent"}

Exclusion criteria

• {"criterion_text":"- Patient unable to give informed consent\n- 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.\n- Curatorship, wardship\n- History of previous vaccination with PCV-7 or PCV-13 or PCV-20\n- History of PPV-23 in the previous year\n- 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.\n- Patient with history of bone marrow transplantation\n- Patient with haemotological malignancies\n- Patient under chemotherapy for solid tumor or with a history of chemotherapy in the past three months\n- Patient treated with Rituximab currently or in the past 6 months\n- Impossibility of providing comprehensible information to the patient\n- Patient with qSOFA score ≥ 2 at randomization (acute severe febrile illness)\n- Patient hospitalized in an Intensive Care Unit\n- Pregnancy\n- Breastfeeding woman\n- Recipients of polyclonal gammaglobulins in the past three months\n- Inability to follow the protocol\n- Bleeding disorder contra-indicating intramuscular injection according to the investigator\n- History of allergy to PCV-20 or vaccine-related components."}

Primary endpoints

• {"endpoint_text":"- 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.\n- 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.","definition_or_measurement_approach":"Primary endpoints measured at 1 month post-vaccination. ‘Immune good responder’ defined by seroconversion (2-fold increase in VT IgG for ≥10 of 13 tested serotypes AND ELISA IgG >1.3 μg/mL in ≥10 of 13 VT) OR alternative definition using 4-fold increase. Measurement via ELISA IgG assays on specified serotypes."}

Secondary endpoints

• {"endpoint_text":"- 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\n- Proportion of immune good responders serotype by serotype at one month post vaccination (ELISA 2-fold increase and ELISA IgG > 1,3μg/mL).\n- OPA IgG titers for serotype by serotype at one month post vaccination in both groups measured a posteriori among immune good responders\n- 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)\n- Number of low respiratory tract infections events in both arms until one year after vaccination.\n- Number of confirmed S.pneumoniae infections in both arms until one year after inclusion\n- Description of richness and diversity of gut microbioma before vaccination associated with people qualified as immune good responders in both arms\n- 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.\n- 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)\n- 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)\n- Proportion of volunteers with salivary IgA (specific of pneumococcus) in both arms at one month post vaccination","definition_or_measurement_approach":"Secondary endpoints include safety (AE counts, local/systemic reactions) assessed in month post-vaccination; serotype-specific immunogenicity by ELISA (2-fold increase and IgG threshold >1.3 μg/mL); opsonophagocytic activity (OPA) titers measured a posteriori among responders; 1-year immunogenicity and clinical outcomes (low respiratory tract infection events, confirmed S. pneumoniae infections) tracked up to 1 year; gut microbiome richness/diversity analyses pre-vaccination; transcriptomics (baseline and 24h) and serum cytokines; T cell IFNg ELISpot/flow cytometry for selected site; salivary IgA measurement at 1 month."}

France

Earliest CTIS Part Ii Submission Date

31-12-2024

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

197

Number Of Sites

24

Number Of Participants

1160

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Saint Etienne

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France