Safety and Immunogenicity of 1 or 2 Doses of IPV in Latin American Infants Primed With Bivalent OPV Vaccine

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)

Sponsors

Lead Sponsor: Fidec Corporation

Collaborator: Bill and Melinda Gates Foundation
Centers for Disease Control and Prevention

Source 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.

Overall Status Completed
Start Date May 2013
Completion Date December 2014
Primary Completion Date April 2014
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in the stool poliovirus excretion after mOPV2 challenge (shedding index) Within 28 days of mOPV2 challenge
Seroconversion and seroprotection to type 1, 2 and 3 poliovirus At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge
Secondary Outcome
Measure Time Frame
Comparability of seroconversion and seroprotection from different IPV vaccines At 6 and 14 weeks, and then before and 1 week after mOPV2 challenge
Safety of each vaccine (tOPV, bOPV, mOPV, Sanofi IPV, GSK IPV and SII IPV) and each vaccine schedule 10 months for each subject
Enrollment 1420
Condition
Intervention

Intervention Type: Biological

Intervention Name: Bivalent Oral Polio Vaccine (bOPV)

Description: Produced by Sanofi Pasteur, Lyon, France, bivalent OPV vaccine contains types 1 and 3 polioviruses and it is indicated for supplementary immunization activities in children from 0 to 5 years of age to prevent or contain outbreaks caused by these 2 serotypes.

Intervention Type: Biological

Intervention Name: Trivalent Oral Polio Vaccine (tOPV)

Description: Produced by Sanofi Pasteur, Lyon, France, trivalent OPV vaccine contains types 1, 2, and 3 polioviruses and it is indicated for routine and supplementary prevention of poliomyelitis in children from 0 to 5 years of age.

Arm Group Label: G3: Trivalent OPV Control

Intervention Type: Biological

Intervention Name: Monovalent Oral Polio Vaccine Type 2 (mOPV2)

Description: Licensed monovalent OPV type 2 vaccine (mOPV2) by Glaxo SmithKline, Rixensart, Belgium. Polio Sabin Mono Two (oral) is a monovalent, live attenuated poliomyelitis virus vaccine of the Sabin strain Type 2 (P 712, Ch, 2ab), propagated in MRC5 human diploid cells.

Intervention Type: Biological

Intervention Name: Sanofi-Pasteur IPV (Sanofi IPV)

Description: Inactivated poliovirus vaccine is produced by Sanofi-Pasteur as a sterile suspension of 3 types of poliovirus. Each dose of vaccine (0.5 mL) contains 40 D antigen units of Mahoney strain (Type 1); 8 D antigen units of MEF-1 strain (Type 2); and 32 D antigen units of Saukett strain (Type 3).

Intervention Type: Biological

Intervention Name: Glaxo SmithKline IPV (GSK IPV)

Description: Inactivated poliovirus vaccine is produced by Glaxo SmithKline, Rixensart, Belgium, as a sterile suspension of 3 types of poliovirus. Each dose of vaccine (0.5 mL) contains 40 D antigen units of Mahoney strain (Type 1); 8 D antigen units of MEF-1 strain (Type 2); and 32 D antigen units of Saukett strain (Type 3).

Intervention Type: Biological

Intervention Name: Serum Institute of India IPV (SII IPV)

Description: Inactivated poliovirus vaccine produced by Nederland's Vaccin Instituut in Bilthoven, The Netherlands (acquired recently by Serum Institute of India [SII]) is licensed in the producing country and prequalified by the WHO. It consists of a sterile suspension of 3 types of poliovirus. Each dose of vaccine (0.5 mL) contains 40 D antigen units of Mahoney strain (Type 1); 8 D antigen units of MEF-1 strain (Type 2); and 32 D antigen units of Saukett strain (Type 3).

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.

Gender: All

Minimum Age: 5 Weeks

Maximum Age: N/A

Healthy Volunteers: Accepts Healthy Volunteers

Overall Official
Location
Facility:
Centro de Estudios en Infectologia Pediatrica - CEIP | Cali, Colombia
Hospital Maternidad Nuestra Señora de la Altagracia | Santo Domingo, Dominican Republic
Clinica Niño Sano Hospital Roosevelt | Guatemala, 01011, Guatemala
Hospital del Niño de Panama | Panama, Panama
Location Countries

Colombia

Dominican Republic

Guatemala

Panama

Verification Date

August 2015

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 9
Arm Group

Label: G1: Sanofi bOPV Control

Type: Experimental

Description: 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

Label: G2: Sanofi bOPV Control

Type: Experimental

Description: 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

Label: G3: Trivalent OPV Control

Type: Experimental

Description: 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

Label: G4: Sanofi bOPV, Sanofi IPV

Type: Experimental

Description: 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

Label: G5: Sanofi bOPV, Sanofi 2 IPV

Type: Experimental

Description: 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

Label: G6: Sanofi bOPV, GSK IPV

Type: Experimental

Description: 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

Label: G7: Sanofi bOPV, GSK 2 IPV

Type: Experimental

Description: 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

Label: G8: Sanofi bOPV, SII IPV

Type: Experimental

Description: 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

Label: G9: Sanofi bOPV, SII 2 IPV

Type: Experimental

Description: 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

Study Design Info

Allocation: Randomized

Intervention Model: Factorial Assignment

Primary Purpose: Prevention

Masking: Single (Outcomes Assessor)

Source: ClinicalTrials.gov