Phase 3 Study on Safety and Immunogenicity of 21-Valent Pneumococcal Conjugate Vaccine in Pediatric and Adolescent Populations
- Trial ID
- 2024-512271-13-00
- Protocol
- PSK00010
- Sponsor
- Sanofi Pasteur Inc.
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to characterize the **safety profile** of the 21-valent pneumococcal conjugate vaccine (PCV21) following each and any dose in healthy infants, toddlers, children, and adolescents. This is clinically relevant as it ensures the vaccine's safety across different age groups, which is crucial for its widespread use in pneumococcal immunisation.
Secondary objectives include:
- For children and adolescents (≥2 years of age): To demonstrate the non-inferiority of serotype-specific opsonophagocytic activity (OPA) titer and immunoglobulin type G (IgG) antibody levels induced by PCV21 compared to the 20-valent pneumococcal conjugate vaccine (20vPCV) for all serotypes included in PCV21 at 30 days post-dose, as assessed by geometric mean titer (GMT) and geometric mean concentration (GMC). Additionally, to describe the serotype-specific OPA titer and IgG antibody levels relative to pre-dose values, and to assess the antibody response (IgG) by seroresponse rate.
- For infants (7-11 months of age) and toddlers (12-23 months of age): To describe the antibody response (IgG) induced by PCV21 versus 20vPCV for all serotypes included in PCV21 at 30 days after the last dose, as assessed by the seroresponse rate. In a separate subset, to describe the serotype-specific OPA titer for all serotypes included in PCV21 at 30 days after the last dose.
Participants
The clinical trial involves a total of **692 participants** who are being evaluated for the safety profile of the 21-valent pneumococcal conjugate vaccine (**PCV21**). The study population includes infants aged 7 to 11 months, toddlers aged 12 to 23 months, children aged 2 to 5 years, and children/adolescents aged 6 to 17 years. Both **male and female** participants are included in the trial. Participants are required to be healthy, as determined by a medical evaluation, including medical history and physical examination. Infants and toddlers must have been born at full term or after a gestation period above 28 weeks, with specific birth weight criteria, and must be medically stable. Female adolescents must not be pregnant or breastfeeding and must adhere to effective contraceptive methods if of childbearing potential. The trial population was selected based on their ability to attend all scheduled visits and comply with study procedures. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring that all ethical guidelines are strictly followed.
Plans and Procedures
The clinical trial is designed as a **randomized**, modified **double-blind**, active-controlled, parallel-group study to evaluate the safety and immunogenicity of catch-up vaccination regimens using a 21-valent pneumococcal conjugate vaccine (PCV21) in healthy infants, toddlers, children, and adolescents. The trial aims to compare the **immunogenicity** and safety profile of PCV21 with a 20-valent pneumococcal conjugate vaccine (20vPCV) across different age groups. The study is expected to commence recruitment on May 13, 2025, and conclude by June 11, 2027, with an estimated duration of approximately two years.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (7 months to 17 years), health status, and ability to comply with study procedures. The trial will include follow-up visits to monitor adverse events, **serotype-specific** immunoglobulin type G (IgG) antibody levels, and opsonophagocytic activity (OPA) titers. The end-of-study visit will evaluate the overall safety and immunogenicity outcomes. The expected length of participant involvement is up to 11 months, depending on the vaccination schedule and follow-up requirements.
Participants may be withdrawn from the study if they experience serious adverse events, fail to comply with study procedures, or if the investigator deems it necessary for safety reasons. The primary endpoints include the number of participants reporting immediate adverse events, solicited and unsolicited injection site reactions, and serious adverse events. Secondary endpoints focus on the serotype-specific IgG concentrations and OPA titers across all age groups. The trial will adhere to rigorous scientific and ethical standards to ensure the validity and reliability of the results.
Treatment
The clinical trial involves the administration of **PREVNAR 20®**, a pneumococcal conjugate vaccine formulated as a **suspension for injection**. This vaccine contains pneumococcal polysaccharide serotypes including 6A, 4, 6B, 9V, 14, 18C, 19F, 23F, 33F, 8, 22F, 19A, 15B, 12F, 11A, 7F, 5, 3, 1, and 10A. The vaccine is administered via **intramuscular injection**. The maximum daily dose is 0.5 ml, with a total maximum dose of 1.5 ml over a treatment period of 11 months. The vaccine is not a pediatric formulation and is used as a comparator in the trial.
The study also includes the **Pneumococcal Conjugate Vaccine (PCV)**, which is another pneumococcal conjugate vaccine formulated as a suspension for injection. This vaccine includes the same pneumococcal polysaccharide serotypes as PREVNAR 20®, with the addition of serotype 9N. It is also administered via intramuscular injection, with a maximum daily dose of 0.5 ml and a total maximum dose of 1.5 ml over 11 months. This formulation is specifically designed for pediatric use and serves as the test product in the trial.
Both vaccines are produced by Sanofi Pasteur Inc. and are classified as structurally diverse substances, specifically vaccines. Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the administration protocol. No additional non-experimental treatments, such as placebo or standard-of-care therapy, are specified in the study design.
Efficacy
The efficacy of the 21-valent pneumococcal conjugate vaccine (PCV21) in the clinical trial will be assessed through several primary and secondary endpoints. The primary endpoints include the number of infants (7-11 months of age) and toddlers (12-23 months of age) with serotype-specific immunoglobulin G (**IgG**) concentrations for all serotypes included in PCV21. Additionally, the number of children (2-5 years of age) with serotype-specific opsonophagocytic activity (**OPA**) titers and IgG concentrations for all serotypes included in PCV21 will be evaluated. For children and adolescents (6-17 years of age), the primary endpoint will focus on the number of participants with serotype-specific OPA titers for all serotypes included in PCV21.
Secondary endpoints will further assess the immunogenicity of PCV21. These include the number of children and adolescents (≥2 years of age) with serotype-specific OPA titers and IgG concentrations for all serotypes included in PCV21. The trial will also measure the number of participants across all age groups with serotype-specific IgG concentrations ≥0.35 µg/ml for all serotypes included in PCV21. For infants and toddlers, the percentage with serotype-specific OPA titers ≥ lower limit of quantification (LLOQ) for all serotypes included in PCV21 will be determined.
The efficacy parameters will be collected and analyzed at 30 days post-dose for each age group. The geometric mean concentration (GMC) of IgG antibodies and OPA titers will be used to describe the serotype-specific immune response induced by PCV21 compared to the 20-valent pneumococcal conjugate vaccine (20vPCV). These assessments will provide a comprehensive evaluation of the vaccine's immunogenicity across different age groups.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Aged 7 months to 17 years on the day of inclusion
- Participants who are healthy as determined by medical evaluation including medical history and physical examination
- For infants (7 to 11 MoA) and toddlers (12 to 23 MoA) only : Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥ 2.5 kg or born after a gestation period above 28 (> 28 weeks) through 36 weeks with a birth weight 1.5 kg, and in both cases medically stable as assessed by the investigator
- For adolescents (6 to 17 YoA) only : A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following conditions applies: ls of non-childbearing potential. To be considered of non-childbearing potential, a female must be pre-menarche or surgically sterile. OR is of childbearing potential and agrees to use an effective contraceptive method or abstinence from at least 4 weeks prior to the study vaccine administration until at least 4 weeks after the study vaccine administration. A female participant of childbearing potential must have a negative highly sensitive pregnancy test (urine or serum as required by local regulation) within 25 hours of before the first dose of study vaccine.
- Assent form has been signed and dated by the participant (based on local regulations), and if applicable, and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (LAR) and by an independent witness, if required by local regulations
- Participant and parent(s) / LAR(s) are able to attend all scheduled visits and to comply with all study procedures
Exclusion Criteria
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy
- History of microbiologically confirmed S. pneumoniae infection or disease
- History of seizure or significant stable or progressive neurological disorders such as inflammatory nervous system diseases, encephalopathy, and cerebral palsy
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a product containing any of the same substances
- Laboratory-confirmed thrombocytopenia, or known thrombocytopenia, as reported by the parent(s) / LAR(s), contraindicating intramuscular (IM) injection
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM injection
- Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with study conduct or completion
- Moderate or severe acute illness/infection (according to investigator judgment) or febrile illness (temperature 38.0°C [100.4°F]) on the day of vaccine administration.
- For infants (7 to 11 MoA) and toddlers (12 to 23 MoA) only : Previous vaccination against S. pneumonia
- For children (2 to 5 YoA) and adolescents (6 to 17 YoA) only : previous vaccination with pneumococcal polysaccharide vaccine
- For adolescents (6 to 17 YoA) only : Alcohol, prescription drug, or substance abuse that, in the opinion of the lnvestigator, might interfere with the study conduct or completion
- Receipt of any vaccine in the 4 weeks preceding the vaccine administration or planned receipt of any vaccine in the 4 weeks following the vaccine administration, except for US licensed influenza vaccination, which may be received at least 2 weeks before or 2 weeks after any study vaccination. This exception includes monovalent pandemic influenza vaccines and multivalent influenza vaccines, as applicable per local recommendations
- Receipt of immune globulins, blood or blood-derived products in the past 3 months
- For children (2 to 5 YoA) and adolescents (6 to 17 YoA) only : Receipt of oral or injectable antibiotic therapy within 72 hours prior to the first blood draw
- Participation at the time of study enrollment (or in the 6 weeks preceding the first vaccine administration) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- For adolescents (6 to 17 YoA) only • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily • ldentified as an lnvestigator or employee of the lnvestigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted chiId) of the lnvestigator or employee with direct involvement in the proposed study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Estonia | Not Recruiting | 13 May 2025 | 400 |
 Poland | Not Recruiting | 13 May 2025 | 310 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
PREVNAR 20 ® | Comparator | SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 0.5 | 11 | PRD11390575 |
Pneumococcal Conjugate VaccinePCV | Test | SUSPENSION FOR INJECTION | INTRAMUSCULAR INJECTION | 0.5 | 11 | PRD10933654 |