Clinical trial NCT03239496: A Study to Evaluate Immunogenicity of Intramuscular Full-Dose and Intradermal Fractional Dose of IPV
Official title: A Phase 3, Open-label, Multicenter Randomized Trial to Evaluate Humoral Immunogenicity of Various Schedules of Intramuscular Full-Dose and Intradermal Fractional Dose of Inactivated Polio Vaccine in Latin American Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Poliomyelitis
Lead sponsor: Fidec Corporation
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2017-08-04
Enrollment: 773
Sex: ALL
Minimum age (years): 5
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study will assess and compare the immune response to full-dose inactivated polio vaccines (IPV) via intramuscular (IM) administration and of the fractional dose of inactivated poliovirus vaccine (f-IPV) via intradermal (ID) administration, in different schedule combinations in the Expanded Program on Immunization (EPI) primary series.

Detailed description: This study prioritizes comparisons involving two-dose regimens recently recommended by the World Health Organization (WHO) Strategic Advisory Group of Experts on immunization (SAGE) and Pan American Health Organization (PAHO) in response to global IPV supply shortages 21. Furthermore, the study will provide data on the comparative humoral immunogenicity of various schedules to inform polio immunization policy for the post-eradication era.

The study population will include infants in Dominican Republic and Panama. Absence of wild and circulating vaccine derived polioviruses along with the lack of regular Supplementary Immunization Activities (SIAs) in the Latin America region provide an ideal epidemiologic setting to study polio vaccine immunogenicity.

Infants will receive two or three doses of full-dose IPV IM or f-IPV ID, in two schedules (10, 14 and 36 weeks and 14 and 36 weeks). Immunological and safety assessments will be made after one dose, two doses and three doses.

A total of 773 infants will be enrolled and distributed into 4 groups, according to a randomization scheme. During the study period, infants will be administered other concomitant vaccines according to the national schedules of the participating countries, but the effect, if any, of the concomitant administration on IPV immunogenicity will not be assessed.

Optimum immunogenicity expected from the dose(s) of IPV in the post-eradication era will have to be balanced with the cost and supply constraints of IPV. This study will be critical to determine how many doses of IPV and which schedule are optimal for the post-eradication era after the global cessation of Oral Polio Vaccine (OPV) use.

Eligibility criteria: Inclusion Criteria:

1. Infants of 6 weeks of age (-7 to + 7 days) on date of enrollment.
2. Healthy, as assessed from medical history and physical examination by a study physician,
3. Written informed consent obtained from parents or legal representatives who have been properly informed about the study and are able to comply with planned study procedures.

Exclusion Criteria:

1. Vaccinated with any poliovirus vaccine prior to inclusion,
2. A household contact with OPV vaccination history in the past 4 weeks,
3. HIV infection or pharmacologic immunosuppression,
4. Known allergy to any component of the study vaccines (phenoxyethanol, formaldehyde),
5. Uncontrolled coagulopathy or blood disorder contraindicating intramuscular and intradermal injections,
6. Acute severe febrile illness on day of vaccination deemed by the Investigator(s) to be a contraindication for vaccination,
7. Not suitable for inclusion or is unlikely to comply with the protocol in the opinion of the investigator(s).

Primary outcomes:
measure: Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 2 Doses IPV IM
timeFrame: To be assessed 4 weeks after the last dose
measure: Seroconversion Non-inferiority of 2 Doses IPV IM vs 3 Doses IPV IM
timeFrame: To be assessed 4 weeks after the last dose
measure: Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 3 Doses f-IPV ID
timeFrame: To be assessed 4 weeks after the last dose
Secondary outcomes:
measure: Seroconversion Superiority of 2 Doses IPV IM at Different Schedules
timeFrame: To be assessed 4 weeks after the second dose
measure: Seroconversion Superiority of 2 Dose f-IPV ID at Different Schedules
timeFrame: To be assessed 4 weeks after the second dose
measure: Seroconversion Non-inferiority of 2 Dose f-IPV ID vs 3 Dose IPV IM
timeFrame: To be assessed 4 weeks after the last dose
measure: Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 3 Doses IPV IM
timeFrame: To be assessed 4 weeks after the last dose
measure: Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 2 Doses IPV IM
timeFrame: To be assessed 4 weeks after the last dose
measure: Number of Participants Experiencing SAEs, IMEs and/or Severe Local Reactions
timeFrame: 9 months
Other outcomes:
Locations:
city: Santo Domingo
country: Dominican Republic
facility: Hospital Universitario Nuestra Señora de la Alta Gracia
city: David
country: Panama
facility: Cevaxin Vaccination Center
city: La Chorrera
country: Panama
facility: Cevaxin Vaccination Center
city: Panama city
country: Panama
facility: Cevaxin Vaccination Center
Study officials:
References:
citation: Bandyopadhyay AS, Gast C, Rivera L, Saez-Llorens X, Oberste MS, Weldon WC, Modlin J, Clemens R, Costa Clemens SA, Jimeno J, Ruttimann R. Safety and immunogenicity of inactivated poliovirus vaccine schedules for the post-eradication era: a randomised open-label, multicentre, phase 3, non-inferiority trial. Lancet Infect Dis. 2021 Apr;21(4):559-568. doi: 10.1016/S1473-3099(20)30555-7. Epub 2020 Oct 23.