Safety and Immunogenicity of 1 or 2 Doses of IPV in Latin American Infants Primed With Bivalent OPV Vaccine
- Conditions
- Poliomyelitis
- Interventions
- Biological: Bivalent Oral Polio Vaccine (bOPV)Biological: Trivalent Oral Polio Vaccine (tOPV)Biological: Monovalent Oral Polio Vaccine Type 2 (mOPV2)Biological: Glaxo SmithKline IPV (GSK IPV)Biological: Sanofi-Pasteur IPV (Sanofi IPV)Biological: Serum Institute of India IPV (SII IPV)
- Registration Number
- NCT01831050
- Lead Sponsor
- Fidec Corporation
- Brief Summary
This study is a Phase IV, open, randomized, multi-center, controlled vaccine trial conducted in healthy Latin American infants, utilizing one or two supplemental doses of IPV in children previously vaccinated with 3 doses of bOPV. We will examine the impact of supplemental IPV on stool shedding and humoral immunity, as well as intra-IPV manufacturer comparability, and safety.
- Detailed Description
The world polio eradication effort is near its goal of reducing the number of new cases of polio to zero. However, final and definitive eradication of the disease will require stopping the use of oral polio vaccines (OPV's) which contain live virus and can rarely revert back to disease producing strains. This period will result in a risk of polio re-emergence as immunity will wane while some vaccine poliovirus will still be circulating. Inactivated polio vaccine (IPV) could potentially play a central role during this process but at present barriers of cost and logistics prevent its routine use in resource limited countries, and concerns exist as to whether IPV provides enough immunity in the intestine to reduce the spread of polioviruses in communities once OPV's are stopped. We plan a multi-center trial in Latin America in which we will administer 1 or 2 doses of IPV to children previously vaccinated with an OPV containing type 1 and 3 poliovirus (bOPV), and then assess the shedding in the stool of a type 2 OPV virus administered later. A decrease in the amount of virus shed compared to children not given IPV would indicate that the IPV boosted intestinal immunity, and would suggest that spread of virus in communities could be reduced using this strategy. We will also measure the impact of supplemental IPV's on antibody formation in the blood, which is a marker of protection of the individual from polio disease. A secondary aim will be to compare the immunogenicity and safety of three IPV's produced by different manufacturers. The overall goal will be to inform policy makers in polio eradication regarding the potential role that one or two doses of IPV might play in the final steps toward polio eradication.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1420
- Age: 6 weeks (-7 to +14 days).
- Healthy without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination.
- Written informed consent obtained from 1 or 2 parents or legal guardian as per country regulations
- Previous vaccination against poliovirus.
- Low birth weight (BW <2,500 gm).
- Multiple pregnancy (twins, triplets, etc.),
- Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus (HIV) infection.
- Family history of congenital or hereditary immunodeficiency.
- Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
- Known allergy to any component of the study vaccines.
- Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections.
- Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- Acute severe febrile illness at day of vaccination deemed by the Investigator to be a contraindication for vaccination.
- Member of the subject's household (living in the same house or apartment unit) who has received OPV vaccine in the last 3 months.
- Subject who, in the opinion of the Investigator or sub-Investigator, is unlikely to comply with the protocol or is inappropriate to be included in the study for the safety or the benefit-risk ratio of the subject.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description G5: Sanofi bOPV, Sanofi 2 IPV Bivalent Oral Polio Vaccine (bOPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G1: Sanofi bOPV Control Monovalent Oral Polio Vaccine Type 2 (mOPV2) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G3: Trivalent OPV Control Trivalent Oral Polio Vaccine (tOPV) 100 infants receiving Trivalent Oral Polio Vaccine (tOPV)' at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G3: Trivalent OPV Control Monovalent Oral Polio Vaccine Type 2 (mOPV2) 100 infants receiving Trivalent Oral Polio Vaccine (tOPV)' at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G2: Sanofi bOPV Control Bivalent Oral Polio Vaccine (bOPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G4: Sanofi bOPV, Sanofi IPV Bivalent Oral Polio Vaccine (bOPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G4: Sanofi bOPV, Sanofi IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G6: Sanofi bOPV, GSK IPV Glaxo SmithKline IPV (GSK IPV) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Glaxo SmithKline IPV (GSK IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G7: Sanofi bOPV, GSK 2 IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Glaxo SmithKline IPV (GSK IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G2: Sanofi bOPV Control Monovalent Oral Polio Vaccine Type 2 (mOPV2) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G1: Sanofi bOPV Control Bivalent Oral Polio Vaccine (bOPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G4: Sanofi bOPV, Sanofi IPV Sanofi-Pasteur IPV (Sanofi IPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G8: Sanofi bOPV, SII IPV Serum Institute of India IPV (SII IPV) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Serum Institute of India IPV (SII IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G5: Sanofi bOPV, Sanofi 2 IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G5: Sanofi bOPV, Sanofi 2 IPV Sanofi-Pasteur IPV (Sanofi IPV) 210 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 dose of Sanofi-Pasteur IPV (Sanofi IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G7: Sanofi bOPV, GSK 2 IPV Bivalent Oral Polio Vaccine (bOPV) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Glaxo SmithKline IPV (GSK IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G9: Sanofi bOPV, SII 2 IPV Bivalent Oral Polio Vaccine (bOPV) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Serum Institute of India IPV (SII IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G6: Sanofi bOPV, GSK IPV Bivalent Oral Polio Vaccine (bOPV) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Glaxo SmithKline IPV (GSK IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G6: Sanofi bOPV, GSK IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Glaxo SmithKline IPV (GSK IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G8: Sanofi bOPV, SII IPV Bivalent Oral Polio Vaccine (bOPV) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Serum Institute of India IPV (SII IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G8: Sanofi bOPV, SII IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 50 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 1 dose of Serum Institute of India IPV (SII IPV) at 14 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 18 weeks G7: Sanofi bOPV, GSK 2 IPV Glaxo SmithKline IPV (GSK IPV) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Glaxo SmithKline IPV (GSK IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G9: Sanofi bOPV, SII 2 IPV Monovalent Oral Polio Vaccine Type 2 (mOPV2) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Serum Institute of India IPV (SII IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks G9: Sanofi bOPV, SII 2 IPV Serum Institute of India IPV (SII IPV) 190 infants receiving Bivalent Oral Polio Vaccine (bOPV) at 6, 10 and 14 weeks and 2 doses of Serum Institute of India IPV (SII IPV) at 14 and 36 weeks with Monovalent Oral Polio Vaccine Type 2 (mOPV2) challenge at 40 weeks
- Primary Outcome Measures
Name Time Method Change in the stool poliovirus excretion after mOPV2 challenge (shedding index) Within 28 days of mOPV2 challenge The basis for calculation of the quantitative shedding index endpoint is to measure the change of viral concentrations shed in stool post-mOPV2 challenge from the baseline timepoint at day 0 to 7, 14, 21 and 28 days as measured from time of mOPV challenge. Quantitative shedding index endpoint will be computed as an area under the viral shedding curve based on these three log10-transformed measurements.
Seroconversion and seroprotection to type 1, 2 and 3 poliovirus At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge The first serologic response endpoint is neutralizing antibody titer defined as the estimated dilution at which 50% neutralizing activity is achieved. The second serologic response endpoint is the binary seroconversion indicator. Seroconversion is considered to be achieved by the time of the subsequent time point if type-specific titers measured at that time are ≥1:8 and \> 4-fold over expected levels of maternally-derived antibody computed from the observed titer at baseline assuming an exponential decay with ½ life of 24 days. The third serologic response endpoint of seroprotection is a binary outcome computed from a single antibody titer measurement with seroprotection being achieved if the measured titer is \> 1:8.
- Secondary Outcome Measures
Name Time Method Comparability of seroconversion and seroprotection from different IPV vaccines At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge To determine whether IPVs from different manufacturers (Sanofi, GSK, SII) are comparable in their ability to induce/boost an antibody response to the 3 poliovirus serotypes in infants vaccinated with 1 or 2 IPV doses after receiving 3 doses of bOPV at 6, 10, and 14 weeks of age
Safety of each vaccine (tOPV, bOPV, mOPV, Sanofi IPV, GSK IPV and SII IPV) and each vaccine schedule 10 months for each subject 1. Number of severe adverse events (SAE)throughout the study period
2. Number of important medical events (IME) as protocol defined: up to 28 days post-vaccination
3. Number of Local \& systemic solicited AEs: 3 days post-vaccination
Trial Locations
- Locations (4)
Hospital del Niño de Panama
🇵🇦Panama, Panama
Hospital Maternidad Nuestra Señora de la Altagracia
🇩🇴Santo Domingo, Dominican Republic
Centro de Estudios en Infectologia Pediatrica - CEIP
🇨🇴Cali, Colombia
Clinica Niño Sano Hospital Roosevelt
🇬🇹Guatemala, Guatemala