Phase I/II Clinical Trial of 26-valent Pneumococcal Conjugate Vaccine

Phase 1

• Conditions: Pneumococcal Vaccines
• Interventions: Biological: 26-Valent pneumococcal conjugate vaccine; Biological: 13-Valent pneumococcal conjugate vaccine; Biological: 23-Valent pneumococcal polysaccharide vaccine

• Registration Number: NCT06703203
• Lead Sponsor: Beijing Zhifei Lvzhu Biopharmaceutical Co., Ltd

Brief Summary

The purpose of this experiment is to evaluate the safety and immunogenicity of the 26 valent pneumococcal conjugate vaccine in the population aged 2 months and above.

Detailed Description

A single-center, randomized, double-blind, active-controlled trial design (Phase I/II) was used. In addition, according to the requirements in the approval letter of this product (2024LP01053), serum standards need to be established for the newly added types (24F, 35B). Therefore, a calibration group is set and an open study design is adopted.

Study Timeline

• Study Start: 2024-08-27
• Study First Submitted: 2024-11-21
• Study First Submitted QC: 2024-11-21
• Study First Posted: 2024-11-25
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-23
• Last Update Posted: 2025-01-27
• Primary Completion: 2025-12-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 450

Inclusion Criteria

• The subject is 2-3 months old (minimum 6 weeks old), 7 months old and above at the time of enrollment, and the legal guardian and/or the subject can provide legal identification certificate;
• The subjects themselves and/or their legal guardians understand the vaccination and trial procedures, voluntarily participate in the trial and sign the informed consent form;
• The subject and/or legal guardian can comply with the clinical trial protocol, have the ability to use thermometer, scale and fill in diary card and contact card as required;
• Female subjects of childbearing potential agree to take effective contraceptive measures from enrollment to 6 months after vaccination.
• For calibration group subjects: 18 to 55 years of age, ≥ 50 kg for males or ≥ 45 kg for females.

Exclusion Criteria

• Axillary body temperature ≥ 37.3 ℃ on the day of enrollment;

• History of infectious diseases caused by Streptococcus pneumoniae confirmed by bacterial culture within 3 years;

• Have received or plan to receive a Streptococcus pneumoniae vaccine outside the trial protocol, including marketed or other investigational Streptococcus pneumoniae vaccines;

• Pregnant or lactating women; Previous history of severe allergy to any vaccine or drug, such as urticaria, dyspnea, angioneurotic edema, anaphylactic shock, Henoch-Schonlein purpura, thrombocytopenic purpura;

• Allergic to any component of the investigational vaccine;

• Suffering from severe respiratory diseases (such as severe asthma), heart diseases, liver diseases, kidney diseases, congenital malformations, developmental disorders and genetic defects (including but not limited to: down syndrome, thalassemia major, etc.) that may interfere with the conduct or completion of the trial;

• Diagnosed with congenital or acquired immunodeficiency, or suspected to have serious chronic disease or systemic disease that may interfere with the conduct or completion of the trial, such as: active tuberculosis, human immunodeficiency virus (HIV) infection, etc.;

• Encephalopathy, uncontrolled epilepsy, convulsion and other progressive neurological diseases, or a history or family history of mental illness;

• Contraindications for intramuscular injection such as thrombocytopenia, any coagulation disorder or receiving anticoagulant therapy;

• Asplenia or splenectomy, functional asplenia due to any condition;

• Immunosuppressant therapy, cytotoxic therapy or corticosteroid therapy within 3 months prior to vaccination, such as systemic glucocorticoid therapy for more than 2 consecutive weeks, such as prednisone or similar drugs > 5 mg/day (excluding corticosteroid spray therapy for allergic rhinitis, surface corticosteroid therapy for acute non-complicated dermatitis);

• Received blood products or immunoglobulins within 3 months prior to enrollment (hepatitis B immunoglobulin is acceptable), or planned to be used during the trial (before the last immunogenicity blood sample collection);

• Within 3 days before the first dose of vaccine, the patient has acute illness or is in acute attack of chronic disease, or has used antipyretic, analgesic or anti-allergic drugs (such as: acetaminophen, ibuprofen, aspirin, etc.);

• Received non-live vaccine within 7 days (≤ 7 days) or live attenuated vaccine within 14 days (≤ 14 days) prior to enrollment;

• Hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg, applicable to adults);

• Abnormal and clinically significant laboratory test results, which are not suitable for enrollment as determined by the investigator (applicable to subjects aged 2 years and older in Phase I);

• Birth weight < 2.5 kg, premature delivery (gestational age < 37 weeks), history of abnormal labor process, history of asphyxia rescue, history of nerve organ damage, history of pathological jaundice confirmed by diagnosis;

• For Standardised Subjects:

  ① Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 50 U/L; Or hemoglobin ≤ 115 g/L (female)/120g/L (male); Any positive serology for hepatitis B, hepatitis C, HIV, or syphilis.

• Plans to move before the end of the trial or leave the area for an extended period of time during scheduled trial visits;

• Ongoing participation or planning to participate in other clinical trials (vaccines, drugs, medical devices, etc.) in the near future;

• Subject has any condition that, in the opinion of the investigator, may interfere with the evaluation of the objectives of the trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2-5 years old age group (for phase Ⅰ/Ⅱ)	13-Valent pneumococcal conjugate vaccine	There are total 230 people in 2-5 years old age group. Among them, there were 30 subjects included in the phase Ⅰ clinical trial and were randomly assigned to the experimental group and the control group in a 2:1 ratio. And the other 200 people were included for phase Ⅱ and were randomly assigned to the experimental group and the control group in a 1:1 ratio.
6-17 years old age group (for phase Ⅰ)	23-Valent pneumococcal polysaccharide vaccine	There are 30 subjects in 6-17 years old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
3 months old age group (for phase Ⅰ)	13-Valent pneumococcal conjugate vaccine	There are 30 subjects in 3 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
2 months old age group （for phase Ⅰ）	13-Valent pneumococcal conjugate vaccine	There are 30 subjects in 2 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
18-59 years old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are total 40 subjects in 18-59 age group. Among them, 30 subjects were randomly assigned to the experimental group and the control group in a 2:1 ratio. In addition, other 10 subjects aged 18-55 to receive the experimental vaccine as the serum calibration test population.
18-59 years old age group (for phase Ⅰ)	23-Valent pneumococcal polysaccharide vaccine	There are total 40 subjects in 18-59 age group. Among them, 30 subjects were randomly assigned to the experimental group and the control group in a 2:1 ratio. In addition, other 10 subjects aged 18-55 to receive the experimental vaccine as the serum calibration test population.
≥60 years old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in ≥60 years old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
≥60 years old age group (for phase Ⅰ)	23-Valent pneumococcal polysaccharide vaccine	There are 30 subjects in ≥60 years old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
6-17 years old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in 6-17 years old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
2-5 years old age group (for phase Ⅰ/Ⅱ)	26-Valent pneumococcal conjugate vaccine	There are total 230 people in 2-5 years old age group. Among them, there were 30 subjects included in the phase Ⅰ clinical trial and were randomly assigned to the experimental group and the control group in a 2:1 ratio. And the other 200 people were included for phase Ⅱ and were randomly assigned to the experimental group and the control group in a 1:1 ratio.
13-23 months old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in 13-23 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
13-23 months old age group (for phase Ⅰ)	13-Valent pneumococcal conjugate vaccine	There are 30 subjects in 13-23 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
7-11 months old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in 7-11 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
7-11 months old age group (for phase Ⅰ)	13-Valent pneumococcal conjugate vaccine	There are 30 subjects in 7-11 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
3 months old age group (for phase Ⅰ)	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in 3 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.
2 months old age group （for phase Ⅰ）	26-Valent pneumococcal conjugate vaccine	There are 30 subjects in 2 months old age group, randomly assigned to the experimental group and the control group in a 2:1 ratio.

Primary Outcome Measures

Name	Time	Method
AE occurrences within 0-30 days after each dose of vaccination (for phase Ⅰ/Ⅱ）	30 day after each vaccination	All AE occurrences within 0-30 days after each dose of vaccination (number of cases, incidence rate, and relationship with vaccination)
Solicited AE occurrences within 0-30 minutes after each dose of vaccination (for phase Ⅰ/Ⅱ）	30 minutes after each vaccination	The occurrence of Solicited adverse events (AE) within 0-30 minutes after each dose of vaccination (number of cases, incidence rate, and relationship with vaccination)
Solicited AE occurrences within 0-7 days after each dose of vaccination (for phase Ⅰ/Ⅱ）	0-7 days after each vaccination	The occurrence of solicited adverse events (AE) within 0-7 days after each dose of vaccination (number of cases, incidence rate, and relationship with vaccination);
Unsolicited AE occurrences within 0-30 days after each dose of vaccination (for phase Ⅰ/Ⅱ）	0-30 days after each vaccination	The occurrence of unsolicited adverse events (AE) within 0-30 days after each dose of vaccination (number of cases, incidence rate, and relationship with vaccination);
Grade 3 and above AE occurrences within 0-30 days after each dose of vaccination (for phase Ⅰ/Ⅱ）	0-30 days after each vaccination	The occurrence of grade 3 and above adverse events within 0-30 days after each dose of vaccination (number of cases, incidence rate, and relationship with vaccination).
All SAE occurrences within 0-6 months after vaccination (for Phase Ⅱ)	0-6 months after each vaccination	The occurrence of all serious adverse reactions within 6 months after vaccination (number of cases, incidence rate, and relationship with vaccination)
Positive rate of serotype-specific pneumococcal IgG antibody on the 30th day after immunization in subjects aged 2-5 years （for phase Ⅱ）	30 day after vaccination	Proportion of subjects with serotype-specific pneumococcal IgG antibody concentration ≥ 0.35 μg/ml on Day 30 after vaccination in subjects aged 2-5 years

Secondary Outcome Measures

Name	Time	Method
All SAE in the population aged ≥12 months during 0-6 months after vaccination （for phase Ⅰ）	0-6 months after vaccination	All SAE in the population aged 12 months and older from the first dose to 6 months after the full course of vaccination
All SAE in the population aged <12 months from the first dose to 6 months after the primary immunization and from the booster to 6 months after the booster（for phase Ⅰ）	From the first dose to 6 months after the primary immunization and from the booster to 6 months after the booster	All SAE from the first dose to 6 months after the primary immunization and from the booster to 6 months after the booster in the population less than 12 months of age.
Proportion of IgG antibodies ≥ 1.0 µg/mL and GMC results on Day 30 post-immunization（for phase Ⅱ）	30 day after vaccination	Proportion of subjects with serotype-specific pneumococcal IgG antibodies ≥ 1.0 µg/mL and GMC results on Day 30 post-immunization in subjects 2 to 5 years of age.

Trial Locations

Locations (1)

Henan Provincial Center for Disease Control and Prevention; 🇨🇳 Shangqiu, Henan, China