Immunogenicity of 1 or 2 Doses of bOPV in Chilean Infants Primed With IPV Vaccine (IPV002ABMG)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Miguel O'Ryan Gallardo, University of Chile
ClinicalTrials.gov Identifier:
NCT01841671
First received: April 19, 2013
Last updated: May 19, 2014
Last verified: April 2014
  Purpose

The rationale for this study (IPV 002ABMG) is to evaluate and compare three doses of IPV, two doses of IPV plus one bOPV, and one dose of IPV plus two doses of bOPV in order to provide evidence for better immunization policy making in regions of the world that must switch to use of IPV/bOPV schedules in the 2014-2015 time frame. The goal is to identify the best option optimizing humoral immune responses, intestinal immunity and thereby prevent community transmission as well as preventing VAPP. Specifically, the study seeks to show that both of the sequential regimens are equivalent (not-inferior) to the 3-dose IPV regimen in the seroconversion rates to both type 1 and type 3 poliovirus such that not more than 10% of subjects fall below the 95% confidence interval observed for the 3-dose IPV alone regimen and the geometric mean titers (GMTs) are no more than 2/3 logs less than those for the 3-dose IPV regimen. In addition, the study will evaluate by a novel method (poliovirus shedding index), the adequacy of IPV vaccines in inducing intestinal immunity, specifically by reducing the shedding of poliovirus type 2 after an OPV challenge. The hypotheses of the study are:

  • A 3-dose IPV/bOPV sequential schedule including 1 or 2 doses of bOPV is non-inferior in terms of types 1 and 3 seroconversion rates and GMTs to a 3-dose IPV schedule.
  • Two and possibly 1 IPV dose(s) provides significant seroconversion rates and GMTs to type 2 poliovirus and sufficient priming to induce a rapid immune response in the context of an oral challenge at 7 months of age.
  • Three, 2, and possibly 1 dose of IPV will induce intestinal immunity to poliovirus type 2 as measured by a combination of quantity of virus in stools and duration of shedding (shedding index).

In addition to these 3 hypotheses, the study will explore the following hypothesis:

• Co-administration of bOPV and rotavirus at 16 weeks of age (the second rotavirus dose) provides similar antirotavirus IgA seroconversion rates and GMCs compared to subjects receiving rotavirus vaccine together with IPV.


Condition Intervention Phase
Polio
Biological: IPV
Biological: bOPV
Biological: mOPV type 2
Biological: Rotarix
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 4, Randomized, Open-Label Study to Assess Humoral and Intestinal Polio Immunity Following a Three-Dose Trivalent Inactivated Polio Vaccine Schedule Relative to Two Sequential Schedules of IPV/Bivalent Oral Polio Vaccines

Resource links provided by NLM:


Further study details as provided by University of Chile:

Primary Outcome Measures:
  • Types 1 and 3 poliovirus humoral immune response [ Time Frame: 12 months ] [ Designated as safety issue: No ]

    Two primary endpoints will be used as the basis for evaluation of the IPV/OPVb sequential regimens compared to three doses of IPV:

    • Seroconversion to type 1 (type-specific titers ≥1:8 and > 4-fold over expected levels of maternally-derived antibody) and GMTs achieved at 28 weeks.
    • Seroconversion to type 3 (type-specific titers ≥1:8 and > 4-fold over expected levels of maternally-derived antibody) and GMTs achieved at 28 weeks.


Secondary Outcome Measures:
  • Poliovirus Type 2 humoral and intestinal immune response and safety [ Time Frame: 12 months (18 months for intestinal immunity) ] [ Designated as safety issue: Yes ]
    • Seroconversion to type 2 (type-specific titers ≥1:8 and > 4-fold over expected levels of maternally-derived antibody) and GMTs achieved after 1 dose of IPV at 16 weeks, after 2 doses at 24 weeks, after 3 doses at 28 weeks, and after the mOPV type 2 challenge dose at 29 weeks.
    • Viral shedding index for type 2 virus following mOPV2 challenge (28-day area under the curve [AUC] of quantitative virus shedding at Days 7, 14, and 21 post-mOPV2 challenge).
    • Safety Endpoints: SAEs as defined in the protocol throughout the study period and IMEs as defined in the protocol up to 28 days post-vaccination.


Other Outcome Measures:
  • antirotavirus IgA seroconversion rates [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    • Antirotavirus IgA seroconversion (> 20 units/mL) and GMCs after the second dose of RotarixTM at 16 weeks of age.


Estimated Enrollment: 570
Study Start Date: April 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPV/IPV/IPV/Rotarix/mOPV type 2
190 healthy infants due for their first dose of polio vaccines will be receive IPV, IPV, IPV at 8, 16 and 24 weeks of age respectively, Rotarix at 8 and 16 weeks if parents accept (optional), and mOPV type 2 at 28 weeks of age
Biological: IPV
Blood samples for poliovirus neutralizing antibodies to be obtained as follows: Group 1 at weeks 8, 16, 28 and 29; Group 2 and 3 at 8, 24, 28 and 29. Stool samples for poliovirus cuantification, for all groups, to be obtained at weeks 28, 29, 30, 31, 32.
Other Name: Sanofi IPV
Biological: mOPV type 2
Administered at 28 weeks of age to all study participants
Other Name: GSK mOPV type 2
Biological: Rotarix
Administered at 8 and 16 weeks to all study participants accepting to recive this vaccine
Other Name: GSK Rotarix
Active Comparator: IPV/IPV/bOPV/Rotarix/mOPV type 2
190 healthy infants due for their first dose of polio vaccines will be receive IPV, IPV, bOPV at 8, 16 and 24 weeks of age respectively and Rotarix at 8 and 16 weeks f age (optional) and mOPV type 2 at 28 weeks of age
Biological: IPV
Blood samples for poliovirus neutralizing antibodies to be obtained as follows: Group 1 at weeks 8, 16, 28 and 29; Group 2 and 3 at 8, 24, 28 and 29. Stool samples for poliovirus cuantification, for all groups, to be obtained at weeks 28, 29, 30, 31, 32.
Other Name: Sanofi IPV
Biological: bOPV
As indicated
Other Name: Sanofi bOPV
Biological: mOPV type 2
Administered at 28 weeks of age to all study participants
Other Name: GSK mOPV type 2
Biological: Rotarix
Administered at 8 and 16 weeks to all study participants accepting to recive this vaccine
Other Name: GSK Rotarix
Active Comparator: IPV/bOPV/bOPV/Rotarix/mOPV type 2
190 healthy infants due for their first dose of polio vaccines will be receive IPV, bOPV, bOPV at 8, 16 and 24 weeks of age respectively and Rotarix at 8 and 16 weeks of age (optional)and mOPV type 2 at 28 weeks of age
Biological: IPV
Blood samples for poliovirus neutralizing antibodies to be obtained as follows: Group 1 at weeks 8, 16, 28 and 29; Group 2 and 3 at 8, 24, 28 and 29. Stool samples for poliovirus cuantification, for all groups, to be obtained at weeks 28, 29, 30, 31, 32.
Other Name: Sanofi IPV
Biological: bOPV
As indicated
Other Name: Sanofi bOPV
Biological: mOPV type 2
Administered at 28 weeks of age to all study participants
Other Name: GSK mOPV type 2
Biological: Rotarix
Administered at 8 and 16 weeks to all study participants accepting to recive this vaccine
Other Name: GSK Rotarix

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   7 Weeks to 9 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Age: 8 weeks (-7 to +7 days).
  2. Healthy infants of all ethnicities and both genders 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 parent or legal guardian who, in the opinion of the investigator, is capable of understanding and complying with the protocol requirements.

Exclusion Criteria:

  1. Previous vaccination against poliovirus.
  2. Low birth weight (BW <2,500 grams).
  3. Twins or multiple pregnancy infants.
  4. Another family or household member who has received OPV within the past 6 months or is going to receive OPV within the following 6 months.
  5. Any confirmed or suspected immunosuppressive or immunedeficient condition including human immunodeficiency virus (HIV) infection.
  6. Family history of congenital or hereditary immunodeficiency.
  7. Major congenital defects or serious chronic illness (neurologic, pulmonary, gastrointestinal, hepatic, renal, or endocrine).
  8. Known allergy to any component of the study vaccines.
  9. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections.
  10. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
  11. Subject who, in the opinion of the 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01841671

Locations
Chile
Facultad de Medicina de la Universidad de Chile
Santiago, Region Metropolitana, Chile, 8380453
Sponsors and Collaborators
University of Chile
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Miguel L O'Ryan, MD University of Chile
  More Information

Publications:
Responsible Party: Miguel O'Ryan Gallardo, Full Professor and Associate Director for Innovation, Faculty of Medicine, University of Chile, University of Chile
ClinicalTrials.gov Identifier: NCT01841671     History of Changes
Other Study ID Numbers: IPV002ABMG
Study First Received: April 19, 2013
Last Updated: May 19, 2014
Health Authority: Chile: Instituto de Salud Pública de Chile

Keywords provided by University of Chile:
Polio
IPV
bOPV
mOPV
vaccination

ClinicalTrials.gov processed this record on October 20, 2014