Phase IV Study of Concomitant Administration of the sIPV and HepA

Official title

Phase IV Study of Evaluating Immunogenicity and Safety of Concomitant Administration of Sabin-strain-based Inactivated Poliovirus Vaccine (Vero Cells) and Freeze-dried Live-attenuated Hepatitis A Vaccine or Inactivated Hepatitis A Vaccine

Overview

This study is a randomized, open-labeled phase IV clinical trial to evaluate the immunogenicity and safety of concomitant administration of sIPV and HepA-L or HepA-I in children aged 18 months. The primary immunogenicity endpoints in all groups are the seroconversion rates of type I, II, and III anti-poliovirus neutralizing antibodies and the seroconversion rate of anti-hepatitis A virus antibodies 30 days after the final administration. The secondary immunogenicity endpoints are (1) the GMT/GMC of type I, II, and III anti-poliovirus neutralizing antibodies as well as the anti-hepatitis A virus antibodies 30 days after the final administration; (2) the seropositive rates of the anti-hepatitis A virus antibodies 30 days after the final administration; (3) the GMFI of type I, II, and III anti-poliovirus neutralizing antibodies as well as the anti-hepatitis A virus antibodies 30 days after the final administration. The secondary safety endpoints are the incidence of adverse events (AEs) within 30 minutes after each injection, the incidence of solicited local and systematic AEs in the period of solicitation after each injection, the incidence of unsolicited AEs in 30 days after each injection, the incidence of AEs in 30 days after each injection, and the incidence of serious adverse events in 6 months after administrations.

Detailed description

This is a randomized, open-labeled, parallel phase IV clinical trial to evaluate the immunogenicity and safety of concomitant administration of sIPV and HepA-L or HepA-I. 2000 children subjects aged 4 months will be enrolled to take administration of 1 dose of sIPV. All participants at 18 months of age will be randomly assigned to 5 cohorts in a ratio of 4:4:4:3:3, that is, (1) 400 subjects will be concomitantly injected with sIPV and HepA-L, (2) 400 subjects will be concomitantly injected with sIPV and HepA-I, and another dose of HepA-I at 24 months of age (3) 400 subjects will be only injected one dose of sIPV, (4) 300 subjects will be only injected with one dose of HepA-L, (5) 300 subjects will be only injected with two doses of HepA-I at 18 and 24 months of age, respectively.

For safety assessment, adverse events after the third dose of sIPV at 4 months of age would be collected through phone-call follow-ups on Day 8 and Day 30 after the injection by investigators and active reports from participants' guardians. At 18 months of age, safety data would be recorded through the diary and contact cards by participants' guardians to collect solicited or unsolicited AEs in periods of solicitation and nonsolicitation, respectively. From 31 days after the final dose to 6 months later, serious adverse events will be evaluated by the investigator via phone call or active reports by participants' guardians.

For immunogenicity assessment, blood samples before each dose on Day 0 and Day 30 after each injection would be collected to evaluate the type I, II, and III anti-poliovirus neutralizing antibody levels or/and anti-hepatitis A virus antibody for different groups.

Interventions

• Biological sIPV (booster dose at 18 months of age)
  Sabin-strain-based inactivated vaccine (Vero cells), 0.5mL for each dose at 18 months of age for the booster one
• Biological HepA-L
  Freeze-dried/lyophilized live-attenuated hepatitis A virus vaccine, 1.0mL for each dose at 18 months of age
• Biological HepA-I
  Inactivated hepatitis A virus vaccine, 0.5mL for each dose, two doses at 18 and 24 months of age, respectively

Primary outcome measures

• Immunogenicity index-seroconversion rate of type I anti-poliovirus neutrilizing antibody [Time frame: Between baseline and day 30 after vaccination]
• Immunogenicity index-seroconversion rate of type II anti-poliovirus neutrilizing antibody [Time frame: Between baseline and day 30 after vaccination]
• Immunogenicity index-seroconversion rate of type III anti-poliovirus neutrilizing antibody [Time frame: Between baseline and day 30 after vaccination]
• Immunogenicity index-seropositive rate of type I anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-seropositive rate of type II anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-seropositive rate of type III anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-seroconversion rate of anti-hepatitis A virus antibody [Time frame: Between baseline and day 30 after vaccination]

Secondary outcome measures (12)

• Immunogenicity index-geometric mean titer (GMT) of type I anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-geometric mean titer (GMT) of type II anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-geometric mean titer (GMT) of type III anti-poliovirus neutrilizing antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-geometric mean concentration (GMC) of anti-hepatitis A virus antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-seropositive rate of anti-hepatitis A virus antibody [Time frame: Day 30 after vaccination]
• Immunogenicity index-geometric mean fold increase (GMFI) of type I anti-poliovirus neutrilizing antibody [Time frame: Between baseline and Day 30 after vaccination]
• Immunogenicity index-geometric mean fold increase (GMFI) of type II anti-poliovirus neutrilizing antibody [Time frame: Between baseline and Day 30 after vaccination]
• Immunogenicity index-geometric mean fold increase (GMFI) of type III anti-poliovirus neutrilizing antibody [Time frame: Between baseline and Day 30 after vaccination]
• Immunogenicity index-geometric mean fold increase (GMFI) of anti-hepatitis A virus antibody [Time frame: Between baseline and Day 30 after vaccination]
• Safety index-incidence of adverse events [Time frame: 0-30 minutes after vaccination]
• Safety index-incidence of solicited adverse events [Time frame: Day 0-7 or Day 0-14 after vaccination]
• Safety index-incidence of unsolicited adverse events [Time frame: Day 0-30 after vaccination]

Eligibility criteria

Inclusion criteria

• Age Requirement: Children aged 4 months at the time of enrollment
• Vaccination Requirement: volunteers have already taken administration 2 doses of sabin-strain-based inactivated poliovirus vaccine (produced by IMBCAMS), and have not yet been injected with the third dose containing poliovirus antigen.
• Provision of Legal Identification: Volunteers and their legal guardians or appointed representatives must provide valid legal identification documents.
• Informed Consent: Legal guardians or appointed representatives of volunteers must have the capacity to understand the informed consent document and the research process, voluntarily participate, and sign the informed consent form.
• Adherence: Legal guardians or appointed representatives of volunteers must be able to comply with the requirements in the study as well as complete relevant visits on time.
• Birth condition: Full-term birth (37\~42 gestational weeks) and normal birth weight (no less than 2500g).
• Temperature Requirement: Axillary body temperature prior to vaccination is less than 37.3°C.

Exclusion criteria

• Health Requirement: Volunteers cannot meet health requirements through physical examinations.
• History of Related Illness: Volunteers have a history of developing Hepatitis A, poliomyelitis, or immunodeficiency.
• Birth Condition: Volunteers have a history of abnormal labor stage, asphyxia, nervous system damage, or clinically confirmed pathologic jaundice。
• Allergic History: Volunteers have a history of allergies to any component of the investigational vaccine (e.g., aluminum hydroxide), any history of vaccine allergies, suspected allergies, or any other severe adverse reactions.
• Vaccine History: Volunteers received any inactivated vaccines or subunit vaccines within 7 days (including the 7th day) prior to vaccination with the investigational vaccine, or any other live attenuated vaccines within 14 days (including the 14th day) prior to vaccination.
• Acute Illness: Volunteers have experienced acute illnesses (e.g., fever) within 3 days prior to vaccination with the investigational vaccine.
• Neurological and Mental Health: Volunteers have a history of seizures, convulsions, cerebral palsy, epilepsy, mental illness, or a family history of such conditions.
• Health Conditions: Volunteers have known congenital abnormalities, developmental disorders, genetic defects, or severe malnutrition, among other conditions.
• Coagulation Abnormalities: Volunteers have a history of coagulation disorders (e.g., coagulation factor deficiency, coagulation disorders).
• Infectious Diseases: Volunteers have infectious diseases that may affect the study, such as human immunodeficiency virus (HIV) infection, hepatitis, and tuberculosis.
• Special Condition: Volunteers who could not tolerate venipuncture, or had a history of needle and blood sickness.
• Organ Removal History: Volunteers have a history of organ removal (e.g., thyroid, pancreas, liver, spleen).
• History of Blood Products: Volunteers have a history of loss of blood, blood transfusion, the use of adjuvant therapies, or immunoglobulin within 3 months prior to vaccination.
• Immune Therapy: Volunteers have received immune-enhancing or immune-suppressing therapy within the last 3 months (continuous oral or intravenous administration for more than 14 days) prior to vaccination.
• Participation in Other Clinical Studies: Volunteers are currently or have plans to participate in other clinical studies before enrollment.
• Investigator's Discretion: The final exclusion criterion is the investigator's discretion to determine whether a volunteer is suitable for participation in the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

China · 3 centers

• Jiu Longpo District Center for Disease Control and Disease — Chongqing
• Wanzhou District Center for DIsease Control and Prevention — Chongqing
• Jiangjin District Center for Disease Control and Prevention — Chongqing

Identifiers

NCT: NCT06460545 · sIPV-402

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗