NCT01841671

Brief Summary

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
570

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Apr 2013

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2013

Completed
18 days until next milestone

First Submitted

Initial submission to the registry

April 19, 2013

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 26, 2013

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

May 20, 2014

Status Verified

April 1, 2014

Enrollment Period

1.1 years

First QC Date

April 19, 2013

Last Update Submit

May 19, 2014

Conditions

Keywords

PolioIPVbOPVmOPVvaccination

Outcome Measures

Primary Outcomes (1)

  • Types 1 and 3 poliovirus humoral immune response

    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.

    12 months

Secondary Outcomes (1)

  • Poliovirus Type 2 humoral and intestinal immune response and safety

    12 months (18 months for intestinal immunity)

Other Outcomes (1)

  • antirotavirus IgA seroconversion rates

    18 months

Study Arms (3)

IPV/IPV/IPV/Rotarix/mOPV type 2

EXPERIMENTAL

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: IPVBiological: mOPV type 2Biological: Rotarix

IPV/IPV/bOPV/Rotarix/mOPV type 2

ACTIVE COMPARATOR

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: IPVBiological: bOPVBiological: mOPV type 2Biological: Rotarix

IPV/bOPV/bOPV/Rotarix/mOPV type 2

ACTIVE COMPARATOR

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: IPVBiological: bOPVBiological: mOPV type 2Biological: Rotarix

Interventions

IPVBIOLOGICAL

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.

Also known as: Sanofi IPV
IPV/IPV/IPV/Rotarix/mOPV type 2IPV/IPV/bOPV/Rotarix/mOPV type 2IPV/bOPV/bOPV/Rotarix/mOPV type 2
bOPVBIOLOGICAL

As indicated

Also known as: Sanofi bOPV
IPV/IPV/bOPV/Rotarix/mOPV type 2IPV/bOPV/bOPV/Rotarix/mOPV type 2
mOPV type 2BIOLOGICAL

Administered at 28 weeks of age to all study participants

Also known as: GSK mOPV type 2
IPV/IPV/IPV/Rotarix/mOPV type 2IPV/IPV/bOPV/Rotarix/mOPV type 2IPV/bOPV/bOPV/Rotarix/mOPV type 2
RotarixBIOLOGICAL

Administered at 8 and 16 weeks to all study participants accepting to recive this vaccine

Also known as: GSK Rotarix
IPV/IPV/IPV/Rotarix/mOPV type 2IPV/IPV/bOPV/Rotarix/mOPV type 2IPV/bOPV/bOPV/Rotarix/mOPV type 2

Eligibility Criteria

Age7 Weeks - 9 Weeks
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)

You may qualify if:

  • Age: 8 weeks (-7 to +7 days).
  • 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.
  • 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.

You may not qualify if:

  • Previous vaccination against poliovirus.
  • Low birth weight (BW \<2,500 grams).
  • Twins or multiple pregnancy infants.
  • 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.
  • Any confirmed or suspected immunosuppressive or immunedeficient condition including human immunodeficiency virus (HIV) infection.
  • Family history of congenital or hereditary immunodeficiency.
  • Major congenital defects or serious 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.
  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Facultad de Medicina de la Universidad de Chile

Santiago, Santiago Metropolitan, 8380453, Chile

Location

Related Publications (6)

  • 1. Global Polio Eradication Initiative. Data and Monitoring: Polio this week. Available at http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx.http://www.polioeradication.org/Dataandmonitoring/Poliothisweek.aspx. Copyright 2010. Accessed 8/23/2012 2. Sixty-fifth World Health Assembly. Poliomyelitis: Intensification of the global eradication initiative. WHA 65.5, Agenda item 13.10; 26 May 2012. 3. Sabin, A B.

    BACKGROUND
  • 2. Sixty-fifth World Health Assembly. Poliomyelitis: Intensification of the global eradication initiative. WHA 65.5, Agenda item 13.10; 26 May 2012.

    BACKGROUND
  • Asturias EJ, Dueger EL, Omer SB, Melville A, Nates SV, Laassri M, Chumakov K, Halsey NA. Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants. J Infect Dis. 2007 Sep 1;196(5):692-8. doi: 10.1086/520546. Epub 2007 Jul 23.

    PMID: 17674310BACKGROUND
  • Minor PD. Polio eradication, cessation of vaccination and re-emergence of disease. Nat Rev Microbiol. 2004 Jun;2(6):473-82. doi: 10.1038/nrmicro906. No abstract available.

    PMID: 15152203BACKGROUND
  • Brickley EB, Wieland-Alter W, Connor RI, Ackerman ME, Boesch AW, Arita M, Weldon WC, O'Ryan MG, Bandyopadhyay AS, Wright PF. Intestinal Immunity to Poliovirus Following Sequential Trivalent Inactivated Polio Vaccine/Bivalent Oral Polio Vaccine and Trivalent Inactivated Polio Vaccine-only Immunization Schedules: Analysis of an Open-label, Randomized, Controlled Trial in Chilean Infants. Clin Infect Dis. 2018 Oct 30;67(suppl_1):S42-S50. doi: 10.1093/cid/ciy603.

  • O'Ryan M, Bandyopadhyay AS, Villena R, Espinoza M, Novoa J, Weldon WC, Oberste MS, Self S, Borate BR, Asturias EJ, Clemens R, Orenstein W, Jimeno J, Ruttimann R, Costa Clemens SA; Chilean IPV/bOPV study group. Inactivated poliovirus vaccine given alone or in a sequential schedule with bivalent oral poliovirus vaccine in Chilean infants: a randomised, controlled, open-label, phase 4, non-inferiority study. Lancet Infect Dis. 2015 Nov;15(11):1273-82. doi: 10.1016/S1473-3099(15)00219-4. Epub 2015 Aug 26.

MeSH Terms

Conditions

Poliomyelitis

Interventions

RIX4414 vaccine

Condition Hierarchy (Ancestors)

MyelitisCentral Nervous System InfectionsInfectionsEnterovirus InfectionsPicornaviridae InfectionsRNA Virus InfectionsVirus DiseasesCentral Nervous System DiseasesNervous System DiseasesSpinal Cord DiseasesNeuroinflammatory DiseasesNeuromuscular Diseases

Study Officials

  • Miguel L O'Ryan, MD

    University of Chile

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Full Professor and Associate Director for Innovation, Faculty of Medicine, University of Chile

Study Record Dates

First Submitted

April 19, 2013

First Posted

April 26, 2013

Study Start

April 1, 2013

Primary Completion

May 1, 2014

Study Completion

June 1, 2014

Last Updated

May 20, 2014

Record last verified: 2014-04

Locations