Clinical Trial of the 24-valent Pneumococcal Polysaccharide Conjugate Vaccine (CRM197/Tetanus Toxoid)

A Randomized, Blinded, Dose-Exploratory, Positive-Control Clinical Trial Evaluating the Safety and Immunogenicity of the 24-Valent Pneumococcal Polysaccharide Conjugate Vaccine (CRM197/Tetanus Toxoid) Following Administration in Individuals Aged 2 Months (Minimum 6 Weeks) and Older

This clinical trial consists of Phase I and Phase II. The objective is to evaluate the safety and immunogenicity of the 24-valent pneumococcal polysaccharide conjugate vaccine (CRM197/tetanus toxoid) in individuals aged 2 months (minimum 6 weeks) and older.

Phase I employs a randomized, blinded, dose-escalation, positive-control design with a total sample size of 310 participants. The study population is divided into five age groups: the 18-49 age group is an open-label design with M and H dose groups; The 7-23-month, 2-5-year-old, and ≥50-year-old groups will use a positive-control, blinded design with M and H dose groups; the 2-month-old (minimum 6 weeks) group will use a positive-control, dose-escalation, and blinded design with L, M, and H dose groups. The Phase II study was divided into two age groups. The ≥50-year-old group: a randomized, blinded, active-controlled design with a total sample size of 160 participants, who were randomly assigned to the treatment and control groups in a 1:1 ratio; the 2-month-old (minimum 6 weeks) group: a randomized, blinded, active-controlled design with a total sample size of 384 participants. Participants were randomly assigned in a 3:1 ratio to the treatment groups (doses L, M, and H) and the control group.

Inclusion Criteria:

Phase I:

• Individuals aged 2 months (minimum 6 weeks), 7 months to 5 years, and 18 years and older who are willing to provide identification
• The trial participant and/or guardian (legal representative) has voluntarily signed the informed consent form after providing informed consent
• Children aged 5 and under who have not previously received a pneumococcal vaccine
• People aged 18 and older who have not received a pneumonia vaccine in the past five years

Phase II (age ≥50 group):

• People aged 50 and older who are willing to provide identification documents
• The trial participants voluntarily signed the informed consent form after providing their informed consent
• People aged 50 and older who have not received a pneumonia vaccine in the past five years

Phase II (2-month-old group (minimum 6 weeks)):

• Individuals aged 2 months or older (minimum 6 weeks) who are willing to provide identification documents
• The guardian (authorized representative) of the trial participant has voluntarily signed the informed consent form after providing informed consent.
• Infants aged 2 months (minimum 6 weeks) who have not previously received a pneumococcal vaccine

Exclusion Criteria:

• Exclusion criteria for the first dose:
• Preterm birth (delivery before 37 weeks of gestation), low birth weight (<2500 g at birth), history of labor abnormalities or resuscitation due to asphyxia; (Applicable to individuals in Phase I and Phase II who are 2 months of age or older (minimum 6 weeks))
• Patients with abnormal results in pre-vaccination blood tests (including complete blood count, blood chemistry, and coagulation function) or urinalysis, which the investigator determines to be clinically significant; (Applicable only to Phase I participants aged 2 years (or 7 months) and older)
• Individuals who are allergic to the active ingredient of the vaccine, any of its inactive ingredients, or substances used in the manufacturing process; or those who have previously experienced an allergic reaction after receiving a similar vaccine; Individuals with a history of severe allergic reactions to vaccines (such as acute allergic reactions, angioedema, or difficulty breathing), or a history of severe allergic reactions to any vaccine, food, or medication, including urticaria, anaphylactic shock, eczema, allergic respiratory distress, angioedema, or a history of asthma
• Individuals with uncontrolled hypertension (as measured on-site: systolic blood pressure ≥160 mmHg and diastolic blood pressure ≥100 mmHg); (Applicable to Stage II participants aged 50 and older and Stage I participants aged 18 and older)
• Women of childbearing age with a positive urine pregnancy test; participants who are breastfeeding; or participants or their partners who plan to become pregnant within the next 6 months; (Applicable to the Phase II group aged 50 or older and the Phase I group aged 18 or older)
• History of epilepsy, seizures (excluding febrile seizures), convulsions, or brain disorders [such as congenital brain malformations, traumatic brain injury, brain tumors, cerebral hemorrhage, cerebral infarction (excluding cerebral infarctions without sequelae and lacunar infarctions), brain infections, chemical poisoning, and other conditions causing damage to brain neural tissue], or a history of mental illness or a family history thereof; or those with other progressive neurological diseases
• Have been diagnosed with a congenital or acquired immunodeficiency, HIV infection, lymphoma, leukemia, systemic lupus erythematosus (SLE), juvenile rheumatoid arthritis (JRA), or other autoimmune diseases
• Known or suspected acute illness or severe chronic disease (including severe respiratory disease, severe cardiovascular disease, liver or kidney disease, severe skin disease, malignant tumors, etc.); or currently experiencing an acute exacerbation of a chronic condition
• Clinically diagnosed coagulation disorders (such as coagulation factor deficiencies, coagulation disorders, or platelet abnormalities) or significant bruising or bleeding disorders
• Asplenia, functional asplenia, and asplenia or splenectomy resulting from any cause
• Patients who have received immunosuppressive therapy within 6 months prior to vaccination or who are scheduled to receive such therapy between enrollment and 1 month after completion of the vaccination series (e.g., long-term systemic corticosteroid use for ≥14 days at a dose >2 mg/kg/day or ≥20 mg/day of prednisone or prednisone-equivalent dose) (excluding topical corticosteroids such as inhaled, nasal spray, intra-articular, eye drops, or ointments; topical use must not exceed the dose recommended in the product label or result in any signs of systemic exposure). Individuals who have used long-acting immunomodulatory drugs (e.g., infliximab) within 6 months prior to the first dose or who plan to use such drugs during the trial (applicable to the Phase II group aged ≥50 years and the Phase I group aged 7 months and older)
• Received blood products (excluding hepatitis B immunoglobulin) within 3 months prior to receiving the investigational drug
• Participation in any other clinical trial involving a drug or vaccine within the 6 months prior to enrollment, or currently participating in such a trial, or plans to participate in such a trial during the study period
• Received an injectable live attenuated vaccine within 14 days prior to receiving the investigational drug, or received any other vaccine within 7 days
• Underarm temperature of 37.3°C or higher prior to vaccination
• According to the researchers' assessment, the trial participants had other factors that made them unsuitable for participation in the clinical trial

Exclusion criteria for the 2nd, 3rd, and 4th doses:

• Individuals who experienced a severe allergic reaction following the previous dose of the vaccine
• Individuals who experienced a serious adverse reaction causally related to a previous dose of the vaccine
• Other potential causes ruled out by the researchers