Back to resultsImmunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine
Primary Purpose
Poliomyelitis
Status
Completed
Phase
Phase 3
Locations
Kenya
Study Type
Interventional
Intervention
BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1
BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2
BioFarma Bivalent Oral Poliomyelitis Vaccine
Sponsored by
About this trial
This is an interventional prevention trial for Poliomyelitis
Eligibility Criteria
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
Sites / Locations
- Kenya Medical Research Institute/Walter Reed Project
- Kenya Medical Research Institute (KEMRI)/Walter Reed Project
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Active Comparator
Arm Label
BBIBP bOPV Lot 1
BBIBP bOPV Lot 2
BioFarma bOPV
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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).
Secondary Outcome Measures
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.
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.
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.
Full Information
NCT ID
NCT02434770
First Posted
April 30, 2015
Last Updated
February 25, 2020
Sponsor
PATH
Collaborators
Beijing Bio-Institute Biological Products Co., Ltd., formerly Beijing TiantanBio
1. Study Identification
Unique Protocol Identification Number
NCT02434770
Brief Title
Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
August 2015 (undefined)
Primary Completion Date
June 17, 2016 (Actual)
Study Completion Date
June 17, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
Beijing Bio-Institute Biological Products Co., Ltd., formerly Beijing TiantanBio
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Poliomyelitis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
750 (Actual)
8. Arms, Groups, and Interventions
Arm Title
BBIBP bOPV Lot 1
Arm Type
Experimental
Arm Description
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.
Arm Title
BBIBP bOPV Lot 2
Arm Type
Experimental
Arm Description
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.
Arm Title
BioFarma bOPV
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 1
Other Intervention Name(s)
Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
BBIBP Bivalent Oral Poliomyelitis Vaccine Lot 2
Other Intervention Name(s)
Poliomyelitis (Live) Vaccine Type I Type III (Human Diploid Cell), Oral
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
BioFarma Bivalent Oral Poliomyelitis Vaccine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Number of Participants Experiencing Any Systemic Reactogenicity, by Maximum Severity
Description
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)
Title
Number of Participants Experiencing Adverse Events
Description
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).
Title
Anti-polio Neutralizing Antibody Geometric Mean Titers (GMT): Serotype 1
Description
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.
Time Frame
Screening and 4 weeks post vaccination 4 (Week 18)
Title
Anti-polio Neutralizing Antibody Geometric Mean Titers: Serotype 3
Description
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.
Time Frame
Screening and 4 weeks post vaccination 4 (Week 18)
Title
Number of Infants With Serotype-specific Anti-polio Neutralizing Antibody Seroconversion 4 Weeks After Last Dose
Description
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).
Time Frame
4 weeks post vaccination 4 (Week 18)
Secondary Outcome Measure Information:
Title
Anti-hepatitis B Surface Antigen (HBsAg) Geometric Mean Titers
Description
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)
Title
Number of Infants With Anti-hepatitis B Surface Antigen (HBsAg) Seroprotection
Description
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
Title
Anti-Rotavirus Immunoglobulin A (IgA) Geometric Mean Titers
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
14 Days
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jessica Cowden, MD, MSPH
Organizational Affiliation
US Army Medical Research Unit-Kenya
Official's Role
Study Chair
Facility Information:
Facility Name
Kenya Medical Research Institute/Walter Reed Project
City
Kisumu
State/Province
Nyanza
ZIP/Postal Code
PO Box 54-40100
Country
Kenya
Facility Name
Kenya Medical Research Institute (KEMRI)/Walter Reed Project
City
Kericho
Country
Kenya
12. IPD Sharing Statement
Learn more about this trial
Immunogenicity and Safety of Liquid Bivalent Oral Poliomyelitis Vaccine
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