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)

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



Sponsors


Source

Fidec Corporation

Oversight Info

Has Dmc

Yes


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

2013-05-01

Completion Date

2014-12-01

Primary Completion Date

2014-04-01

Phase

Phase 4

Study Type

Interventional

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

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


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.

Arm Group Label

G1: Sanofi bOPV Control

G2: Sanofi bOPV Control

G4: Sanofi bOPV, Sanofi IPV

G5: Sanofi bOPV, Sanofi 2 IPV

G6: Sanofi bOPV, GSK IPV

G7: Sanofi bOPV, GSK 2 IPV

G8: Sanofi bOPV, SII IPV

G9: Sanofi bOPV, SII 2 IPV


Other Name

Bivalent Oral Polio Vaccine

bOPV



Intervention Type

Biological

Intervention Name


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

Other Name

"OPVERO"

Trivalent Oral Polio Vaccine

tOPV



Intervention Type

Biological

Intervention Name


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.

Arm Group Label

G1: Sanofi bOPV Control

G2: Sanofi bOPV Control

G3: Trivalent OPV Control

G4: Sanofi bOPV, Sanofi IPV

G5: Sanofi bOPV, Sanofi 2 IPV

G6: Sanofi bOPV, GSK IPV

G7: Sanofi bOPV, GSK 2 IPV

G8: Sanofi bOPV, SII IPV

G9: Sanofi bOPV, SII 2 IPV


Other Name

Polio Sabin Mono Two

Monovalent Oral Polio Vaccine Type 2

mOPV2



Intervention Type

Biological

Intervention Name


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).

Arm Group Label

G4: Sanofi bOPV, Sanofi IPV

G5: Sanofi bOPV, Sanofi 2 IPV


Other Name

Sanofi-Pasteur IPV

IPOL

IMOVAX

Sanofi IPV



Intervention Type

Biological

Intervention Name


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).

Arm Group Label

G6: Sanofi bOPV, GSK IPV

G7: Sanofi bOPV, GSK 2 IPV


Other Name

Glaxo SmithKline IPV

POLIORIX

(GSK IPV)



Intervention Type

Biological

Intervention Name


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).

Arm Group Label

G8: Sanofi bOPV, SII IPV

G9: Sanofi bOPV, SII 2 IPV


Other Name

Serum Institute of India IPV

SII IPV




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

Last Name

Role

Affiliation

Edwin J Asturias, MD
Principal Investigator
University of Colorado, Denver
Ricardo Ruttimann, MD
Study Director
Fidec Corporation

Overall Contact

Last Name

Edwin J Asturias, MD

Phone

(303)7246282

Email



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

Country

Colombia

Dominican Republic

Guatemala

Panama



Verification Date

2015-08-01

Lastchanged Date

2015-08-04

Firstreceived Date

2013-04-10

Responsible Party

Responsible Party Type

Sponsor


Keywords


Is Fda Regulated

No

Has Expanded Access

No

Condition Browse


Number Of Arms

9

Intervention Browse

Mesh Term

Vaccines


Arm Group

Arm Group Label

G1: Sanofi bOPV Control

Arm Group 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


Arm Group Label

G2: Sanofi bOPV Control

Arm Group 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


Arm Group Label

G3: Trivalent OPV Control

Arm Group 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


Arm Group Label

G4: Sanofi bOPV, Sanofi IPV

Arm Group 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


Arm Group Label

G5: Sanofi bOPV, Sanofi 2 IPV

Arm Group 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


Arm Group Label

G6: Sanofi bOPV, GSK IPV

Arm Group 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


Arm Group Label

G7: Sanofi bOPV, GSK 2 IPV

Arm Group 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


Arm Group Label

G8: Sanofi bOPV, SII IPV

Arm Group 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


Arm Group Label

G9: Sanofi bOPV, SII 2 IPV

Arm Group 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



Firstreceived Results Date

N/A

Overall Contact Backup

Last Name

Ricardo Ruttimann, MD

Email



Firstreceived Results Disposition Date

N/A

Study Design Info

Allocation

Randomized

Intervention Model

Factorial Assignment

Primary Purpose

Prevention

Masking

Single (Outcomes Assessor)


Study First Submitted

April 10, 2013

Study First Submitted Qc

April 11, 2013

Study First Posted

April 15, 2013

Last Update Submitted

August 4, 2015

Last Update Submitted Qc

August 4, 2015

Last Update Posted

October 12, 2017


ClinicalTrials.gov processed this data on October 12, 2017

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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