Immunogenicity of Intramuscular and Intradermal IPV (IM and ID IPV)

Immunogenicity of Intramuscular and Intradermal Inactivated Poliovirus Vaccine in Routine Immunization

This is an open-label phase IV randomized clinical trial that will compare immune responses among infants who receive different dose schedules of either fractional dose or full dose inactivated poliovirus vaccine (IPV), delivered either intramuscularly or intradermally.

Note: This study was terminated early due to the COVID-19 pandemic. Due to early study closure, the study objectives could not be evaluated as planned. Both of the primary objectives and several secondary objectives could not be evaluated because none of the study participants reached the corresponding endpoint. Due to limited sample size, the analysis approach for four secondary objectives was changed from a non-inferiority assessment to a comparison of proportions between groups.

Study Overview

• Status: Terminated
• Conditions: Poliomyelitis
• Intervention / Treatment: Biological: IPV; Biological: fIPV (0.1 mL) ID; Biological: fIPV (0.1mL) IM; Biological: fIPV (0.2mL) IM

Detailed Description

Oral poliovirus vaccine (OPV) cessation is essential to achieve eradication of polio as OPV contains live poliovirus, which can mutate and become neurovirulent. After OPV cessation, inactivated poliovirus vaccine (IPV) will be the only polio vaccine used for routine immunization. This clinical trial will provide poliovirus type-specific immunogenicity data on an IPV or fractional-dose IPV (fIPV)-only schedule for routine immunization, which will be important for post OPV cessation era. For fIPV, it will provide immunogenicity data on fIPV administered either intradermally (ID) or intramuscularly (IM) and allow a direct comparison of the two methods.

Healthy infants 6 weeks of age will be enrolled at two study clinics in Dhaka, Bangladesh, and randomized to one of seven study arms. Infants will be followed-up until 10 months of age through clinic visits. Blood specimens will be collected to test for immunological response.

• Study Type: Interventional
• Enrollment (Actual): 958
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • icddr,b study clinics (Mirpur and CTU Dhaka)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 month (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy infants 6 weeks of age
• Parents that consent for participation in the full length of the study.
• Parents that are able to understand and comply with planned study procedures.

Exclusion Criteria:

• Parents and infants who are unable to participate in the full length of the study.
• A diagnosis or suspicion of immunodeficiency disorder either in the infant or in an immediate family member.
• A diagnosis or suspicion of bleeding disorder that would contraindicate parenteral administration of IPV or collection of blood by venipuncture.
• Acute diarrhoea, infection or illness at the time of enrolment (6 weeks of age) that would require infant's admission to a hospital.
• Acute vomiting and intolerance to liquids within 24 hours before the enrolment visit (6 weeks of age).
• Evidence of a chronic medical condition identified by a study medical officer during physical exam.
• Receipt of any polio vaccine (OPV or IPV) before enrolment based upon documentation or parental recall.
• Known allergy/sensitivity or reaction to polio vaccine, or its contents.
• Infants from multiple births. Infants from multiple births will be excluded because the infant(s) who is/are not enrolled would likely receive OPV through routine immunization and transmit vaccine poliovirus to the enrolled infant. Even if all births from a multiple birth could be enrolled in the study, we will exclude multiple births as discontinuation of one may lead to discontinuation of multiple participants.
• Infants from premature births (<37 weeks of gestation).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: IPV at 14 weeks + 9 months; Participants in this arm will receive full doses (0.5 mL) of IPV at 14 weeks and 9 months of age.	Biological: IPV; Full dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.5 milliliter (mL) dose by intramuscular (IM) injection.
ACTIVE_COMPARATOR: IPV at 6 weeks + 9 months; Participants in this arm will receive full doses (0.5 mL) of IPV at 6 weeks and 9 months of age.	Biological: IPV; Full dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.5 milliliter (mL) dose by intramuscular (IM) injection.
ACTIVE_COMPARATOR: fIPV ID at 6 weeks + 14 weeks + 9 months; Participants in this arm will receive intradermal fractional doses (0.1 mL) of IPV at 6 weeks, 14 weeks, and 9 months of age.	Biological: fIPV (0.1 mL) ID; Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.1 milliliter (mL) dose (fractional) by intradermal (ID) injection in lieu of the full 0.5 mL dose.
ACTIVE_COMPARATOR: fIPV ID at 14 weeks + 9 months; Participants in this arm will receive intradermal fractional doses (0.1 mL) of IPV at 14 weeks and 9 months of age.	Biological: fIPV (0.1 mL) ID; Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.1 milliliter (mL) dose (fractional) by intradermal (ID) injection in lieu of the full 0.5 mL dose.
ACTIVE_COMPARATOR: fIPV IM at 6 weeks + 14 weeks + 9 months; Participants in this arm will receive intramuscular fractional doses (0.1 mL) of IPV at 6 weeks, 14 weeks, and 9 months of age.	Biological: fIPV (0.1mL) IM; Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.1 milliliter (mL) dose (fractional) by intramuscular (IM) injection in lieu of the full 0.5 mL dose.
ACTIVE_COMPARATOR: fIPV 0.1mL IM at 14 weeks + 9 months; Participants in this arm will receive intramuscular fractional doses (0.1 mL) of IPV at 14 weeks and 9 months of age.	Biological: fIPV (0.1mL) IM; Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.1 milliliter (mL) dose (fractional) by intramuscular (IM) injection in lieu of the full 0.5 mL dose.
ACTIVE_COMPARATOR: fIPV 0.2mL IM at 14 weeks + 9 months; Participants in this arm will receive intramuscular fractional doses (0.2 mL) of IPV at 14 weeks and 9 months of age.	Biological: fIPV (0.2mL) IM; Fractional dose of inactivated poliovirus vaccine that protects against types 1, 2, and 3 (all polio serotypes). Given as a 0.2 milliliter (mL) dose (fractional) by intramuscular (IM) injection in lieu of the full 0.5 mL dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vaccine response	Dichotomous (yes/no) variable defined as participants who are either seronegative (<1:8 titers) at baseline who become seropositive (≥1:8) after vaccination (seroconversion) or participants who demonstrate a four-fold rise in titers after vaccination between two specimens, e.g. a change from 1:8 to 1:32, after adjusting for expected decay in maternal antibodies. Antibody titers at 6 weeks of age will be the starting point for the expected decline in maternal antibodies, assuming at half-life of 28 days.	Measured four weeks after administration of study vaccine(s).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reciprocal antibody titers	Variable of the observed reciprocal antibody titer results.	Measured four weeks after administration of study vaccine(s).

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: International Centre for Diarrhoeal Disease Research, Bangladesh

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2019
• Primary Completion (ACTUAL): March 25, 2020
• Study Completion (ACTUAL): March 25, 2020

Study Registration Dates

• First Submitted: August 19, 2019
• First Submitted That Met QC Criteria: August 19, 2019
• First Posted (ACTUAL): August 21, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2022
• Last Update Submitted That Met QC Criteria: May 11, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: intramuscular; inactivated poliovirus vaccine; fractional inactivated poliovirus vaccine; intradermal
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Neuromuscular Diseases; Central Nervous System Infections; Enterovirus Infections; Picornaviridae Infections; Spinal Cord Diseases; Myelitis; Poliomyelitis
• Other Study ID Numbers: 19058

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No