Comparison of Immunogenicity of Inactivated Poliovirus Vaccine (IPV) Administered Intramuscularly or Intradermally

• ClinicalTrials.gov Identifier: NCT04027036
• Recruitment Status: Enrolling by invitation
• First Posted: July 19, 2019
• Last Update Posted: September 5, 2021
• Sponsor: Instituto Nacional de Saúde, Mozambique
• Collaborator: World Health Organization
• Information provided by (Responsible Party): Instituto Nacional de Saúde, Mozambique

Study Description

Brief Summary:

Polio is an acute transmissible disease caused by any of the three polio virus serotypes (types 1, 2 or 3). In Mozambique, polio vaccination is part of the immunization schedule of the expanded vaccination program. The oral vaccine (OPV) is administered at months 0,2,3, and 4 and a single dose of the inactivated poliovirus vaccine (IPV) is given intramuscularly at month 4. In 2016 shortage of IPV supply caused stock-outs and put strain on IPV use for routine immunizations as well as for poliovirus outbreak response. Therefore, assessment of new vaccine regimens using smaller doses of IPV are needed. Administration of fractionated IPV (fIPV), i.e., 1/5 (0.1mL) of the standard dose, intradermally has shown to be safe and to provide an immune response similar to the standard dose of IPV that is currently given intramuscularly. However, intradermal administration of fIPV is technically difficult and many countries are hesitant to adopt fIPV in their routine immunization schedules. Therefore, the investigators need data confirming that the use of the fIPV vaccine intramuscularly is safe and the immune response is not inferior to the use of fIPV intradermally. Study Objective: to compare the immunogenicity of fIPV administered intramuscularly or intradermally in infants at 2 and 4 months of age. Study Hypotheses: the seroconversion rate after administration of one or two doses of fIPV intramuscularly is not inferior to the fIPV intradermally. The priming effect after fIPV administered intramuscularly is not inferior to the fIPV intradermally. Study Methods: This will be a phase II non-inferiority clinical trial. 360 children will be enrolled in two study groups, with prior consent of the parents / guardians. In group I, 180 children will receive 0.1 ml of IPV intramuscularly and in group II 180 children will receive the same dose intradermally. There will not be a group control. The children will be selected at birth at pre-defined health units in Maputo city. The fractional IPV vaccine will be given to children at 2 and 4 months of age during routine vaccinations. In total there will be four study visits, of which the first two are vaccination visits. All visits will be performed at the health units. 1 ml of blood will be collected at each study visit to assess the immune response before and after vaccination. Data will be collected by trained and qualified personnel and in accordance with Good Clinical Practice standards. Adverse events following administration of the vaccine will be monitored and all serious adverse events will be reported to ethics and regulatory committees, and to World Health Organization (WHO). Evaluation of the immune response: Seroconversion rates and priming effect will be evaluated. Serum will be tested for the presence of neutralizing antibodies against poliovirus using standard neutralization assays and immunogenicity will be assessed by titration of anti-polio 2 immunoglobulin G.

Condition or disease	Intervention/treatment	Phase
Polio	Biological: Inactivated poliovirus vaccine in reduced doses	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 360 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Clinical Trial to Compare the Immunogenicity of the Inactivated Poliovirus Vaccine (IPV) Administered in Reduced Doses Intramuscularly or Intradermally in Infants at 2 and 4 Months of Age in the Maputo City
• Actual Study Start Date: August 6, 2020
• Estimated Primary Completion Date: December 20, 2021
• Estimated Study Completion Date: December 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: fIPV Intramuscular; 180 children will receive 0,1 ml of inactivated poliovirus vaccine intramuscularly	Biological: Inactivated poliovirus vaccine in reduced doses; contains the following excipients: 2-phenoxyethanol (2.5 mg), water for injection and diluent solution and phosphate buffer having the following composition: sodium phosphate, sodium chloride, potassium chloride, magnesium sulfate, phenol red and calcium chloride. dosage:0,1ml duration: first dose: month 2 of age; second dose: month 4 of age
Active Comparator: fIPV Intradermal; 180 children will receive 0,1ml of inactivated poliovirus vaccine intradermally	Biological: Inactivated poliovirus vaccine in reduced doses; contains the following excipients: 2-phenoxyethanol (2.5 mg), water for injection and diluent solution and phosphate buffer having the following composition: sodium phosphate, sodium chloride, potassium chloride, magnesium sulfate, phenol red and calcium chloride. dosage:0,1ml duration: first dose: month 2 of age; second dose: month 4 of age

Outcome Measures

Primary Outcome Measures :

1. Seroconversion [ Time Frame: month 5 ]
   Difference in seroconversion between arms as expressed by proportion of seropositive children on final blood collection.

Secondary Outcome Measures :

1. Priming [ Time Frame: month 4+1week ]
   Difference in priming between arms as expressed by proportion of seropositive children on third blood collection among seronegative children at 2nd bleed

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 2 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Children whose parents/guardians consent to their participation;
• Children whose parents/guardians live in the study area and do not intend to depart during the study period.

Exclusion Criteria:

• Children whose parents are under the legal age with exception of 16-years-old parents who are already living in marital status;
• Children whose parents have mental illness;
• Children with immunosuppression.

Contacts and Locations

Locations

Mozambique

Instituto Nacional de Saúde-Mozambique CISPOC

Maputo, Mozambique, 21-462867

INSMozambique

Maputo, Mozambique

Sponsors and Collaborators

Instituto Nacional de Saúde, Mozambique

World Health Organization

Investigators

• Principal Investigator: Edna Viegas, MD,PhD; INS-CISPOC

More Information

Publications:

Mohammed AJ, AlAwaidy S, Bawikar S, Kurup PJ, Elamir E, Shaban MM, Sharif SM, van der Avoort HG, Pallansch MA, Malankar P, Burton A, Sreevatsava M, Sutter RW. Fractional doses of inactivated poliovirus vaccine in Oman. N Engl J Med. 2010 Jun 24;362(25):2351-9. doi: 10.1056/NEJMoa0909383.

Resik S, Tejeda A, Mach O, Fonseca M, Diaz M, Alemany N, Garcia G, Hung LH, Martinez Y, Sutter R. Immune responses after fractional doses of inactivated poliovirus vaccine using newly developed intradermal jet injectors: a randomized controlled trial in Cuba. Vaccine. 2015 Jan 3;33(2):307-13. doi: 10.1016/j.vaccine.2014.11.025. Epub 2014 Nov 22.

Nelson KS, Janssen JM, Troy SB, Maldonado Y. Intradermal fractional dose inactivated polio vaccine: a review of the literature. Vaccine. 2012 Jan 5;30(2):121-5. doi: 10.1016/j.vaccine.2011.11.018. Epub 2011 Nov 17. Review.

Resik S, Tejeda A, Lago PM, Diaz M, Carmenates A, Sarmiento L, Alemañi N, Galindo B, Burton A, Friede M, Landaverde M, Sutter RW. Randomized controlled clinical trial of fractional doses of inactivated poliovirus vaccine administered intradermally by needle-free device in Cuba. J Infect Dis. 2010 May 1;201(9):1344-52. doi: 10.1086/651611.

Cadorna-Carlos J, Vidor E, Bonnet MC. Randomized controlled study of fractional doses of inactivated poliovirus vaccine administered intradermally with a needle in the Philippines. Int J Infect Dis. 2012 Feb;16(2):e110-6. doi: 10.1016/j.ijid.2011.10.002. Epub 2011 Dec 5.

Troy SB, Kouiavskaia D, Siik J, Kochba E, Beydoun H, Mirochnitchenko O, Levin Y, Khardori N, Chumakov K, Maldonado Y. Comparison of the Immunogenicity of Various Booster Doses of Inactivated Polio Vaccine Delivered Intradermally Versus Intramuscularly to HIV-Infected Adults. J Infect Dis. 2015 Jun 15;211(12):1969-76. doi: 10.1093/infdis/jiu841. Epub 2015 Jan 7.

Soonawala D, Verdijk P, Wijmenga-Monsuur AJ, Boog CJ, Koedam P, Visser LG, Rots NY. Intradermal fractional booster dose of inactivated poliomyelitis vaccine with a jet injector in healthy adults. Vaccine. 2013 Aug 12;31(36):3688-94. doi: 10.1016/j.vaccine.2013.05.104. Epub 2013 Jun 13.

Resik S, Tejeda A, Sutter RW, Diaz M, Sarmiento L, Alemañi N, Garcia G, Fonseca M, Hung LH, Kahn AL, Burton A, Landaverde JM, Aylward RB. Priming after a fractional dose of inactivated poliovirus vaccine. N Engl J Med. 2013 Jan 31;368(5):416-24. doi: 10.1056/NEJMoa1202541.

Weldon WC, Oberste MS, Pallansch MA. Standardized Methods for Detection of Poliovirus Antibodies. Methods Mol Biol. 2016;1387:145-76. doi: 10.1007/978-1-4939-3292-4_8.

• Responsible Party: Instituto Nacional de Saúde, Mozambique
• ClinicalTrials.gov Identifier: NCT04027036
• Other Study ID Numbers: fIPV-CISPOC
• First Posted: July 19, 2019
• Last Update Posted: September 5, 2021
• Last Verified: August 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR); Analytic Code

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Instituto Nacional de Saúde, Mozambique:

Vaccine; Polio Virus