Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine

PATH750 enrolled

Overview

The purpose of this study will be to evaluate whether a bivalent oral polio vaccine (bOPV) manufactured by Beijing Bio-Institute Biological Products Co., Ltd (BBIBP) has a similar immunogenicity profile to a WHO prequalified bOPV.

BBIBP has been one of the two suppliers of trivalent oral polio vaccine (tOPV) in China since 1985, with control of polio in China evidence of the effectiveness of its vaccine. The company plans to introduce a liquid formulation of bOPV (types 1 and 3) to meet increasing global demand with the phasing-out of tOPV. The proposed study is intended to provide data sufficient to obtain World Heath Organization (WHO) prequalification for the BBIBP bOPV, thus making the vaccine available to help meet global demand. Infants were enrolled and randomized prior to the birth dose of bOPV. The first dose of study vaccine was administered during the first two weeks of life and then co-administered with the primary Expanded Programme on Immunization (EPI) series vaccines in Kenya at 6, 10 and 14 weeks of age. The Kenya EPI schedule includes the following additional vaccines: * Bacille Calmette-Guérin Vaccine (BCG) at birth * Diphtheria and Tetanus Toxoid with Whole Cell Pertussis, Haemophilus influenzae Type V vaccine (Hib), and Hepatitis B Vaccine (DTwPHibHep) at 6, 10, 14 weeks; * Pneumococcal Conjugate vaccine (PCV) at 6, 10, 14 weeks * Rotavirus vaccine (Rotarix) at 6, 10 weeks

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

SINGLE

Enrollment

750

Conditions

Poliomyelitis

Interventions

BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1BIOLOGICAL

Each dose of bOPV (2 drops, 0.1 ml) contains attenuated Sabin strains of poliovirus serotypes 1 and 3, with at least 10\^6 cell culture infectious dose 50% (CCID50)/dose and 10\^5.8 CCID50/dose, respectively.

BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2BIOLOGICAL

Each dose of bOPV (2 drops, 0.1 ml) contains types 1 and 3 attenuated polioviruses (Sabin), with at least 10\^6 CCID50/dose and 10\^5.8 CCID50/dose, respectively.

BioFarma Bivalent Oral Poliomyelitis VaccineBIOLOGICAL

Each dose of the WHO prequalified Bio Farma bOPV (2 drops, 0.1 ml) contains attenuated Sabin strains of poliovirus serotypes 1 and 3, with at least 10\^6 and 10\^5.8 infective units per dose, respectively.

Eligibility

Sex: ALLMin age: 1 DayMax age: 14 DaysHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy, full-term infants, as established by medical history and clinical examination before entering into the study. * Parents willing to provide written informed consent. * Age: infants less than 2 weeks of age at the time of enrollment (from the 1st through the 14th day of life, inclusive) Exclusion Criteria: * Birth weight (as documented at first medical contact) less than 2.5 kg * Presence of diarrhea or vomiting in the previous 24 hours or on the day of enrollment (temporary exclusion) * Presence of fever (\> 37.5°C) on the day of enrollment (temporary exclusion) * Acute disease at the time of enrollment (temporary exclusion) * Significant malnutrition as per Investigator's judgment * Concurrent participation in another clinical study at any time during the study period in which the infant will be exposed to an investigational or a non-investigational product * Presence of any significant systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer or autoimmune disease) as determined by medical history and/or physical examination which would compromise the child's health or is likely to result in non-conformance to the protocol * Known or suspected impairment of immunological function (including human immunodeficiency virus \[HIV\] exposure) based on medical history and physical examination * Previous receipt of polio virus vaccine * Household contact with a known immunosuppressed individual * Unwillingness or inability of parents for active follow-up by the study staff * History of any neurological disorders or seizures * Any medical condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence or a participant's ability to give informed consent * Maternal HIV infection

Locations (2)

Kenya Medical Research Institute/Walter Reed Project

Kisumu, Nyanza, Kenya

Kenya Medical Research Institute (KEMRI)/Walter Reed Project

Kericho, Kenya

Outcomes

Primary Outcomes

Number of Participants Experiencing Any Systemic Reactogenicity, by Maximum Severity

Solicited systemic reactogenicity events evaluated during the week after each vaccination included fever, vomiting, diarrhea, decreased appetite/ poor feeding, irritability, and decreased activity. Reactions were recorded by participant's parents via memory aid. Each event was graded as: Mild (Grade 1): No or minimal interference with usual activities; no medical intervention/therapy required, Moderate (Grade 2): Greater than minimal interference with usual activities; no or minimal medical intervention/therapy required, Severe (Grade 3): Marked limitation in ability to perform usual activities; medical intervention/therapy required, or Potentially life-threatening (Grade 4): Inability to perform basic functions OR Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death. The overall number of participants who experienced any systemic reaction is reported. Grades are based on maximum severity per participant.

Time frame: 7 days after each vaccination (Weeks 0, 6, 10, and 14)

Number of Participants Experiencing Adverse Events

Adverse events were graded as mild (Grade 1 = No or minimal interference with usual activities; no medical intervention/therapy required), moderate (Grade 2 = Greater than minimal interference with usual activities; no or minimal medical intervention/therapy required), severe (Grade 3 = Marked limitation in ability to perform usual activities; medical intervention/therapy required), or potentially life-threatening (Grade 4 = Inability to perform basic functions OR Medical or operative intervention indicated to prevent permanent impairment, persistent disability, or death). The overall number of participants who experienced any adverse event is reported. Grades are based on maximum severity per participant.

Time frame: From the time of the first vaccination through 28 days after each vaccination (up to Day 126).

Anti-polio Neutralizing Antibody Geometric Mean Titers (GMT): Serotype 1

The assays for determination of anti-poliovirus neutralizing antibodies at the National Institutes for Food and Drug Control (NIFDC) were validated. Anti-polio antibody titer four weeks after the fourth vaccination was adjusted for the decrease in maternal antibodies based on a half-life of 28 days.

Data from ClinicalTrials.gov

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Secondary Outcomes

Anti-hepatitis B Surface Antigen (HBsAg) Geometric Mean Titers

Anti-HBsAg titers were measured to assess the impact of concomitant administration of BBIBP liquid bOPV on immune responses to other Expanded Programme on Immunization (EPI) vaccines in comparison to that of the WHO pre-qualified bOPV, 4 weeks after the fourth vaccination. The enzyme-linked immunosorbent assay (ELISA) assays for serum antibodies to HBsAg were performed at the Children's Hospital Medical Center (CCHMC). The HBsAb assay was a qualified assay using a kit from BioRad.

Time frame: 4 weeks post vaccination 4 (Week 18)

Number of Infants With Anti-hepatitis B Surface Antigen (HBsAg) Seroprotection

Seroprotection was defined as a HBsAg titer ≥ 1:10 The ELISA assays for serum antibodies to HBsAg were performed at the Children's Hospital Medical Center (CCHMC). The HBsAb assay was a qualified assay using a kit from BioRad.

Time frame: 28 days after vaccination 4

Anti-Rotavirus Immunoglobulin A (IgA) Geometric Mean Titers

Anti-rotavirus immunoglobulin A titers were measured to assess the impact of concomitant administration of BBIBP liquid bOPV on immune responses to other Expanded Programme on Immunization (EPI) vaccines in comparison to that of the WHO pre-qualified bOPV, 4 weeks after the fourth vaccination. The ELISA assay for antibodies to rotavirus was performed at the Children's Hospital Medical Center (CCHMC) using a validated in-house assay.

Time frame: 4 weeks post vaccination 4 (Week 18)