Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine

Phase 3

Completed

Conditions: Poliomyelitis

Interventions: Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1
Biological: BioFarma Bivalent Oral Poliomyelitis Vaccine
Biological: BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2

Registration Number: NCT02434770

Lead Sponsor: PATH

Brief Summary: 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: 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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 750

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BBIBP bOPV Lot 1	BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1	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.
BioFarma bOPV	BioFarma Bivalent Oral Poliomyelitis Vaccine	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.
BBIBP bOPV Lot 2	BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2	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.

Primary Outcome Measures

Name	Time	Method
Anti-polio Neutralizing Antibody Geometric Mean Titers (GMT): Serotype 1	Screening and 4 weeks post vaccination 4 (Week 18)	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.
Number of Participants Experiencing Adverse Events	From the time of the first vaccination through 28 days after each vaccination (up to Day 126).	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.
Anti-polio Neutralizing Antibody Geometric Mean Titers: Serotype 3	Screening and 4 weeks post vaccination 4 (Week 18)	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.
Number of Infants With Serotype-specific Anti-polio Neutralizing Antibody Seroconversion 4 Weeks After Last Dose	4 weeks post vaccination 4 (Week 18)	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).
Number of Participants Experiencing Any Systemic Reactogenicity, by Maximum Severity	7 days after each vaccination (Weeks 0, 6, 10, and 14)	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.

Secondary Outcome Measures

Name	Time	Method
Number of Infants With Anti-hepatitis B Surface Antigen (HBsAg) Seroprotection	28 days after vaccination 4	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.
Anti-Rotavirus Immunoglobulin A (IgA) Geometric Mean Titers	4 weeks post vaccination 4 (Week 18)	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.
Anti-hepatitis B Surface Antigen (HBsAg) Geometric Mean Titers	4 weeks post vaccination 4 (Week 18)	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.

Trial Locations

Locations (2): Kenya Medical Research Institute/Walter Reed Project
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Kisumu, Nyanza, Kenya
Kenya Medical Research Institute (KEMRI)/Walter Reed Project
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Kericho, Kenya