Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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A Phase III Single-blind, Randomized, Controlled Study in Healthy Kenyan Infants to Assess the Immunogenicity and Safety of Beijing TiantanBio Liquid Bivalent Oral Poliomyelitis Vaccine (bOPV) in Comparison to a WHO Prequalified Comparator bOPV

Conditions
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Poliomyelitis

Intervention / Treatment
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* Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1
* Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2
* Biological: BioFarma Bivalent Oral Poliomyelitis Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BBIBP bOPV Lot 1<br>Infants received 2 drops of liquid bivalent oral polio vaccine (bOPV) manufactured by BBIBP, Lot 1, administered directly into the mouth in the first two weeks of life, and at 6, 10, and 14 weeks of age. | Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1<br>* 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.<br>* Other names: Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral;|
| Experimental: BBIBP bOPV Lot 2<br>Infants received 2 drops of liquid bivalent oral polio vaccine (bOPV) manufactured by BBIBP, Lot 2, administered directly into the mouth in the first two weeks of life, and at 6, 10, and 14 weeks of age. | Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2<br>* 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.<br>* Other names: Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral;|
| Active Comparator: BioFarma bOPV<br>Infants received 2 drops of WHO prequalified liquid bivalent oral polio vaccine manufactured by BioFarma, administered directly into the mouth in the first two weeks of life, and at 6, 10, and 14 weeks of age. | Biological: BioFarma Bivalent Oral Poliomyelitis Vaccine<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | Screening and 4 weeks post vaccination 4 (Week 18) | 
| Anti-polio Neutralizing Antibody Geometric Mean Titers: Serotype 3 | 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. | Screening and 4 weeks post vaccination 4 (Week 18) | 
| Number of Infants With Serotype-specific Anti-polio Neutralizing Antibody Seroconversion 4 Weeks After Last Dose | The assays for determination of anti-poliovirus neutralizing antibodies at the National Institutes for Food and Drug Control (NIFDC) were validated. Seroconversion was defined as a titer ≥ 1:8 if seronegative at screening, otherwise a ≥ 4-fold increase in adjusted titers (i.e., adjusted for the decay in maternal antibodies, based on a half life of 28 days). | 4 weeks post vaccination 4 (Week 18) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 4 weeks post vaccination 4 (Week 18) |