Clinical trial NCT01831050: Safety and Immunogenicity of 1 or 2 Doses of IPV in Latin American Infants Primed With Bivalent OPV Vaccine
Official title: A Phase 4, Randomized Study to Evaluate the Safety and the Humoral and Intestinal Immunogenicity of One or Two Additional Doses of Licensed Inactivated Polio Vaccines (IPVs) in Latin American Infants Previously Vaccinated With Bivalent Oral Polio Vaccines (bOPVs)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Poliomyelitis
Keywords: Poliovirus
Inactivated poliovirus vaccine
Trivalent oral polio vaccine
Bivalent oral polio vaccine
Stool shedding index
Polio eradication
Lead sponsor: Fidec Corporation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Centers for Disease Control and Prevention
First posted: 2013-04-15
Enrollment: 1420
Sex: ALL
Minimum age (years): 5
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

1. Age: 6 weeks (-7 to +14 days).
2. Healthy without obvious medical conditions that preclude the subject to be in the study as established by the medical history and physical examination.
3. Written informed consent obtained from 1 or 2 parents or legal guardian as per country regulations

Exclusion Criteria:

1. Previous vaccination against poliovirus.
2. Low birth weight (BW \<2,500 gm).
3. Multiple pregnancy (twins, triplets, etc.),
4. Any confirmed or suspected immunosuppressive or immunodeficient condition including human immunodeficiency virus (HIV) infection.
5. Family history of congenital or hereditary immunodeficiency.
6. Major congenital defects or serious uncontrolled chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
7. Known allergy to any component of the study vaccines.
8. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections.
9. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
10. Acute severe febrile illness at day of vaccination deemed by the Investigator to be a contraindication for vaccination.
11. Member of the subject's household (living in the same house or apartment unit) who has received OPV vaccine in the last 3 months.
12. 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.

Primary outcomes:
measure: Change in the stool poliovirus excretion after mOPV2 challenge (shedding index)
timeFrame: Within 28 days of mOPV2 challenge
measure: Seroconversion and seroprotection to type 1, 2 and 3 poliovirus
timeFrame: At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge
Secondary outcomes:
measure: Comparability of seroconversion and seroprotection from different IPV vaccines
timeFrame: At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge
measure: Safety of each vaccine (tOPV, bOPV, mOPV, Sanofi IPV, GSK IPV and SII IPV) and each vaccine schedule
timeFrame: 10 months for each subject
Other outcomes:
Locations:
city: Cali
country: Colombia
facility: Centro de Estudios en Infectologia Pediatrica - CEIP
city: Santo Domingo
country: Dominican Republic
facility: Hospital Maternidad Nuestra Señora de la Altagracia
city: Guatemala
country: Guatemala
facility: Clinica Niño Sano Hospital Roosevelt
city: Panama
country: Panama
facility: Hospital del Niño de Panama
Study officials:
affiliation: University of Colorado, Denver
name: Edwin J Asturias, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fidec Corporation
name: Ricardo Ruttimann, MD
role: STUDY_DIRECTOR
References:
citation: Lopez-Medina E, Melgar M, Gaensbauer JT, Bandyopadhyay AS, Borate BR, Weldon WC, Ruttimann R, Ward J, Clemens R, Asturias EJ. Inactivated polio vaccines from three different manufacturers have equivalent safety and immunogenicity when given as 1 or 2 additional doses after bivalent OPV: Results from a randomized controlled trial in Latin America. Vaccine. 2017 Jun 16;35(28):3591-3597. doi: 10.1016/j.vaccine.2017.04.041. Epub 2017 Apr 25.
citation: Asturias EJ, Bandyopadhyay AS, Self S, Rivera L, Saez-Llorens X, Lopez E, Melgar M, Gaensbauer JT, Weldon WC, Oberste MS, Borate BR, Gast C, Clemens R, Orenstein W, O'Ryan G M, Jimeno J, Clemens SA, Ward J, Ruttimann R; Latin American IPV001BMG Study Group. Humoral and intestinal immunity induced by new schedules of bivalent oral poliovirus vaccine and one or two doses of inactivated poliovirus vaccine in Latin American infants: an open-label randomised controlled trial. Lancet. 2016 Jul 9;388(10040):158-69. doi: 10.1016/S0140-6736(16)00703-0. Epub 2016 May 19.