Immunogenicity of Inactivated and Live Polio Vaccines

This study has been completed.
Sponsor:
Collaborators:
International Centre for Diarrhoeal Disease Research, Bangladesh
Ministry of Health and Family Welfare, Bangladesh
NanoPass Technologies Ltd
Information provided by (Responsible Party):
Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01813604
First received: March 12, 2013
Last updated: January 7, 2014
Last verified: March 2013
  Purpose

This study is an open-label phase III randomized clinical trial that would compare immunogenicity after receiving one of five different combinations of polio vaccines. Infants will be enrolled and randomized at 6 weeks of age to one of five different arms:

A) Three doses of trivalent oral poliovirus vaccine (tOPV) at 6, 10 and 14 weeks of age B) Three doses of bivalent OPV (bOPV) at 6, 10 and 14 weeks of age C) Two doses of intramuscular (IM) inactivated poliovirus vaccine (IPV) at 6 and 14 weeks of age D) Two doses of intra-dermal (ID) fractional IPV (f-IPV) at 6 and 14 weeks of age E) Sequential administration of ID f-IPV at 6 and 14 weeks of age with bOPV at 10 weeks of age To assess the immunogenicity of each study vaccine and vaccination schedule, antibody titers against poliovirus types 1, 2 and 3 will be determined in sera extracted from blood collected before (at 6 weeks of age) and after receiving 3 doses of study vaccine (18 weeks of age). Seroconversion will be defined as a titer 4-fold higher than the expected fall in maternally derived antibodies, assuming a half-life of 28 days. The initial antibody titer at 6 weeks of age will be used as the starting point for the expected decline in maternal antibody.

This study will compare the immunogenicity of:

  1. Sequential dose of intra-dermal f-IPV and bOPV to bOPV alone administered at 6, 10 and 14 weeks of age
  2. tOPV to bOPV administered at 6,10 and 14 weeks of age
  3. IM IPV to ID f-IPV administered at 6 and 14 weeks of age The answer to these questions will guide the global polio eradication program in designing new routine immunization schedule for children that eliminates the risks of paralysis due to vaccine derived poliovirus (VDPV) from type 2 vaccine poliovirus.

Condition Intervention Phase
Poliomyelitis
Biological: Group A: Trivalent Oral Polio Vaccine
Biological: Group B: Bivalent Oral Polio Vaccine
Biological: Group C: Inactivated Polio Vaccine
Biological: Group D: fractional IPV (f-IPV)
Biological: Arm E: f-IPV and bOPV
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase III Clinical Trial to Assess the Immunogenicity of a Sequential Dose of Fractional Inactivated Polio Vaccine (f-IPV) and Oral Polio Vaccine (OPV)

Resource links provided by NLM:


Further study details as provided by Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Seroconversion [ Time Frame: Change in antibody titers at 18 weeks of age compared to 6 weeks of age ] [ Designated as safety issue: No ]

    The primary analytical approach will be intention-to-treat analysis on enrolled participants who have serological results available on blood specimens collected at 18 weeks of age.

    Reciprocal antibody titers of at least 1:8, the lowest detectable titer, is considered to indicate seropositivity with regards to the presence of poliovirus neutralizing antibodies. Seroconversion is defined as either seronegative participants (<1:8 titers) who become seropositive (≥1:8) or participants who demonstrate a 4-fold change in titers between two specimens, e.g. a change from 1:8 to 1:32. To compare the immunogenicity across study arms, the investigators will compare the proportion of participants who seroconvert by 18 weeks of age. Chi-square tests will be used to test the statistical significance among seroconversion rates across study arms.



Secondary Outcome Measures:
  • Poliovirus shedding in stool [ Time Frame: At 19 weeks of age ] [ Designated as safety issue: No ]
    Stool specimens collected a week after a challenge dose of tOPV will be analyzed to determine poliovirus shedding. By study arm the investigators will compare proportion of participants shedding poliovirus overall and by type of poliovirus. The investigators will also evaluate quantitative viral shedding (viral titers) and compare these results by study arm.


Estimated Enrollment: 1206
Study Start Date: November 2012
Study Completion Date: November 2013
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A: Trivalent Oral Polio Vaccine
Group A will receive 3 doses of trivalent oral polio vaccine (tOPV) at 6, 10 and 14 weeks of age. A challenge dose of tOPV will be administered at 18 weeks of age.
Biological: Group A: Trivalent Oral Polio Vaccine
Group A will receive 3 doses of trivalent oral polio vaccine (tOPV) at 6, 10 and 14 weeks of age. A challenge dose of tOPV will be administered at 18 weeks of age.
Active Comparator: Group B: Bivalent Oral Polio Vaccine
Group B will receive 3 doses of bivalent oral polio vaccine (bOPV) at 6, 10 and 14 weeks of age. A challenge dose of tOPV will be administered at 18 weeks of age.
Biological: Group B: Bivalent Oral Polio Vaccine
Group B will receive 3 doses of bivalent oral polio vaccine (bOPV) at 6, 10 and 14 weeks of age. A challenge dose of tOPV will be administered at 18 weeks of age.
Active Comparator: Group C: Inactivated Polio Vaccine
Group C will receive 2 doses of inactivated polio vaccine (IPV) at 6 and 14 weeks of age. IPV will be administered intramuscularly using standard needle and syringe. A challenge dose of tOPV will be administered at 18 weeks of age.
Biological: Group C: Inactivated Polio Vaccine
Group C will receive 2 doses of inactivated polio vaccine (IPV) at 6 and 14 weeks of age. IPV will be administered intramuscularly using standard needle and syringe. A challenge dose of tOPV will be administered at 18 weeks of age.
Active Comparator: Group D: fractional IPV (f-IPV)
Group D will receive 2 doses of fractional inactivated polio vaccine (f-IPV) at 6 and 14 weeks of age. f-IPV (one-fifth dose of IPV) will be administered intradermally using MicroJet 600 microneedle hub by NanoPass Technologies. A challenge dose of tOPV will be administered at 18 weeks of age.
Biological: Group D: fractional IPV (f-IPV)
Group D will receive 2 doses of fractional inactivated polio vaccine (f-IPV) at 6 and 14 weeks of age. f-IPV (one-fifth dose of IPV) will be administered intradermally using MicroJet 600 microneedle hub by NanoPass Technologies. A challenge dose of tOPV will be administered at 18 weeks of age.
Active Comparator: Arm E: f-IPV and bOPV
Group E will receive 2 doses of f-IPV at 6 and 14 weeks of age with bOPV at 10 weeks of age. f-IPV will be administered intradermally using MicroJet 600 microneedle hub by NanoPass Technologies. A challenge dose of tOPV will be administered at 18 weeks of age.
Biological: Arm E: f-IPV and bOPV
Group E will receive 2 doses of f-IPV at 6 and 14 weeks of age with bOPV at 10 weeks of age. f-IPV will be administered intradermally using MicroJet 600 microneedle hub by NanoPass Technologies. A challenge dose of tOPV will be administered at 18 weeks of age.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Weeks to 7 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy infants 6-7 weeks of age
  • Family that consents for participation in the full length of the study
  • Family that is able to understand and comply with planned study procedures

Exclusion Criteria:

  • Family that is unable to participate in the full length of the study
  • A diagnosis or suspicion of immunodeficiency disorder either in the infant or in an immediate family member
  • A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of IPV or collection of blood by venipuncture
  • Acute diarrhea, infection or illness at the time of enrollment (6-7 weeks of age) that would require infant's admission to a hospital or would contraindicate provision of OPV per country guidelines
  • Acute vomiting and intolerance to liquids within 24 hours before the enrollment visit (6 weeks of age)
  • Receipt of any polio vaccine (OPV or IPV) before enrollment based upon documentation or parental recall
  • Known allergy/sensitivity or reaction to polio vaccine or contents of polio vaccine
  • Infants from multiple births. Infants from multiple are excluded to reduce the potential for contact transmission of vaccine poliovirus. The infant from a multiple birth who is not enrolled is likely to receive routine immunization and transmit vaccine poliovirus to the enrolled infant
  • Infants from premature births (<37 weeks of gestation)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01813604

Locations
Bangladesh
Mirpur Health Clinic
Dhaka, Bangladesh
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Ministry of Health and Family Welfare, Bangladesh
NanoPass Technologies Ltd
Investigators
Principal Investigator: Abhijeet Anand, MBBS, MPH Centers for Disease Control and Prevention
Principal Investigator: K. Zaman, MBBS, PhD International Center for Diarrheal Disease Research, Bangladesh
  More Information

No publications provided

Responsible Party: Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01813604     History of Changes
Other Study ID Numbers: ICDDRB-RRC-PR-12028
Study First Received: March 12, 2013
Last Updated: January 7, 2014
Health Authority: United States: Federal Government

Keywords provided by Centers for Disease Control and Prevention:
Polio
Inactivated polio vaccine
oral polio vaccine
vaccine trial

Additional relevant MeSH terms:
Poliomyelitis
Myelitis
Central Nervous System Viral Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Neuromuscular Diseases

ClinicalTrials.gov processed this record on April 14, 2014