CClinicalTrials.gg
Sign In
CompletedNCT03239496Updated Jul 21, 2023Results posted

A Study to Evaluate Immunogenicity of Intramuscular Full-Dose and Intradermal Fractional Dose of IPV

A Phase 3 interventional study of IPV and f-IPV in Poliomyelitis, sponsored by Fidec Corporation. Completed at 4 sites in 2 countries. Open to participants aged 5 Weeks to 7 Weeks, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-07-21.

Sponsored by Fidec Corporation · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
773
Allocation
Randomized
Ages
5 Weeks to 7 Weeks
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Poliomyelitis

Browse trials for

03

Who can participate

Ages eligible
5 Weeks to 7 Weeks
Sexes eligible
All
Accepts healthy volunteers
Yes

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

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).
04

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
773 participants (actual)

Study arms

  • Experimental
    Group A

    3 doses IPV IM at 10, 14 \& 36 weeks of age incl. blood sampling at 10, 14, 18 \& 40 weeks.

    Biological: IPV

  • Experimental
    Group B

    2 doses IPV IM at 14 \& 36 weeks of age incl. blood sampling at 14, 18, 36 \& 40 weeks.

    Biological: IPV

  • Experimental
    Group C

    3 doses f-IPV ID at 10, 14 \& 36 weeks of age incl. blood sampling at 10, 14, 18 \& 40 weeks.

    Biological: f-IPV

  • Experimental
    Group D

    2 doses f-IPV ID at 14 \& 36 weeks of age incl. blood sampling at 14, 18, 36 \& 40 weeks.

    Biological: f-IPV

Interventions

  • BiologicalIPV

    Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)

  • Biologicalf-IPV

    Comparison of different vaccination schedules with 2 different vaccines (IPV and f-IPV) and 2 different types of administration (IM and ID)

05

What researchers measure

Primary outcomes

  1. Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 2 Doses IPV IM

    To determine if the seroconversion rate of a 2-dose intradermally administered fractional-dose inactivated poliovirus vaccine (f-IPV) regimen administered at 14 and 36 weeks of age is non-inferior to that of a 2-dose intramuscularly administered inactivated poliovirus vaccine (IPV) regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

  2. Seroconversion Non-inferiority of 2 Doses IPV IM vs 3 Doses IPV IM

    To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

  3. Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 3 Doses f-IPV ID

    To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

Secondary outcomes

  1. Seroconversion Superiority of 2 Doses IPV IM at Different Schedules

    To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the second dose

  2. Seroconversion Superiority of 2 Dose f-IPV ID at Different Schedules

    To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose f-IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the second dose

  3. Seroconversion Non-inferiority of 2 Dose f-IPV ID vs 3 Dose IPV IM

    To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

  4. Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 3 Doses IPV IM

    To determine if the seroconversion rate of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen also administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

  5. Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 2 Doses IPV IM

    To determine if the seroconversion rate to a 3-dose regimen of f-IPV administered at 10, 14, and 36 weeks of age is non-inferior to that of a 2-dose IPV regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2.

    Time frame: To be assessed 4 weeks after the last dose

  6. Number of Participants Experiencing SAEs, IMEs and/or Severe Local Reactions

    To assess the safety of each vaccine (IPV and f-IPV) as measured by the number of subjects experiencing serious adverse events (SAEs), important medical events (IMEs) and/or severe local reactions. This assessments is done in the Total Vaccinated Population (744 subjects).

    Time frame: 9 months

06

Results

Posted Aug 18, 2020

Participant flow

Participant flow — Overall Study
MilestoneGroup A - 3 Doses IPV IMGroup B - 2 Doses IPV IMGroup C - 3 Doses f-IPVGroup D - 2 Doses f-IPV ID
Started200178178217
Completed186168166203
Not completed14101214

Outcome measures

PrimarySeroconversion Non-inferiority of 2 Doses f-IPV ID vs 2 Doses IPV IM

To determine if the seroconversion rate of a 2-dose intradermally administered fractional-dose inactivated poliovirus vaccine (f-IPV) regimen administered at 14 and 36 weeks of age is non-inferior to that of a 2-dose intramuscularly administered inactivated poliovirus vaccine (IPV) regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 2 Doses IPV IM
percentage of seroconversionGroup BGroup D
Serotype 198.1 (94.6 to 99.6)95.9 (92.1 to 98.2)
Serotype 298.7 (95.5 to 99.8)97.9 (94.8 to 99.4)
Statistical analysis
  • Group B vs Group D · t-test, 1 sided · p = 0.05
PrimarySeroconversion Non-inferiority of 2 Doses IPV IM vs 3 Doses IPV IM

To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non-inferiority of 2 Doses IPV IM vs 3 Doses IPV IM
percentage of seroconversionGroup AGroup B
Serotype 1100 (97.9 to 100)98.1 (94.6 to 99.6)
Serotype 2100 (97.9 to 100)98.7 (95.5 to 99.8)
Statistical analysis
  • Group A vs Group B · t-test, 2 sided · p = 0.05
PrimarySeroconversion Non-inferiority of 2 Doses f-IPV ID vs 3 Doses f-IPV ID

To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non-inferiority of 2 Doses f-IPV ID vs 3 Doses f-IPV ID
percentage of seroconversionGroup CGroup D
Serotype 198.8 (95.6 to 98.8)95.9 (92.1 to 98.2)
Serotype 2100 (97.7 to 100)97.9 (94.8 to 99.4)
Statistical analysis
  • Group C vs Group D · t-test, 2 sided · p = 0.05
SecondarySeroconversion Superiority of 2 Doses IPV IM at Different Schedules

To determine if the seroconversion rate of a 2-dose IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the second dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Superiority of 2 Doses IPV IM at Different Schedules
percentage of seroconversionGroup AGroup B
Serotype 195.6 (94.6 to 99.6)98.1 (94.6 to 99.6)
Serotype 288.9 (83.4 to 93.1)98.7 (95.5 to 99.8)
Statistical analysis
  • Group A vs Group B · Fisher Exact · p = 0.0001
SecondarySeroconversion Superiority of 2 Dose f-IPV ID at Different Schedules

To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is superior to that of a 2-dose f-IPV regimen administered at 10 and 14 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the second dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Superiority of 2 Dose f-IPV ID at Different Schedules
percentage of seroconversionGroup CGroup D
Serotype 183.2 (76.5 to 88.6)95.9 (92.1 to 98.2)
Serotype 283.9 (77.2 to 89.2)97.9 (94.8 to 99.4)
Statistical analysis
  • Group C vs Group D · Fisher Exact · p = 0.0001
SecondarySeroconversion Non-inferiority of 2 Dose f-IPV ID vs 3 Dose IPV IM

To determine if the seroconversion rate of a 2-dose f-IPV regimen administered at 14 and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non-inferiority of 2 Dose f-IPV ID vs 3 Dose IPV IM
percentage of seroconversionGroup AGroup D
Serotype 1100 (97.9 to 100)95.9 (92.1 to 98.2)
Serotype 2100 (97.9 to 100)97.9 (94.8 to 99.4)
Statistical analysis
  • Group A vs Group D · t-test, 2 sided · p = 0.05
SecondarySeroconversion Non Inferiority of 3 Doses f-IPV ID vs 3 Doses IPV IM

To determine if the seroconversion rate of a 3-dose f-IPV regimen administered at 10, 14, and 36 weeks of age is non-inferior to that of a 3-dose IPV regimen also administered at 10, 14, and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 3 Doses IPV IM
percentage of seroconversionGroup AGroup C
Serotype 1100 (97.9 to 100)98.8 (95.6 to 99.8)
Serotype 2100 (97.9 to 100)100 (97.7 to 100)
Statistical analysis
  • Group A vs Group C · t-test, 2 sided · p = 0.05
SecondarySeroconversion Non Inferiority of 3 Doses f-IPV ID vs 2 Doses IPV IM

To determine if the seroconversion rate to a 3-dose regimen of f-IPV administered at 10, 14, and 36 weeks of age is non-inferior to that of a 2-dose IPV regimen administered at 14 and 36 weeks of age for poliovirus serotypes 1 and 2.

Time frame:
To be assessed 4 weeks after the last dose
Reported as:
Mean · percentage of seroconversion
Seroconversion Non Inferiority of 3 Doses f-IPV ID vs 2 Doses IPV IM
percentage of seroconversionGroup BGroup C
Serotype 198.1 (94.6 to 99.6)98.8 (95.6 to 99.8)
Serotype 298.7 (95.5 to 99.8)100 (97.7 to 100)
Statistical analysis
  • Group B vs Group C · t-test, 2 sided · p = 0.05
SecondaryNumber of Participants Experiencing SAEs, IMEs and/or Severe Local Reactions

To assess the safety of each vaccine (IPV and f-IPV) as measured by the number of subjects experiencing serious adverse events (SAEs), important medical events (IMEs) and/or severe local reactions. This assessments is done in the Total Vaccinated Population (744 subjects).

Time frame:
9 months
Reported as:
Count of participants · Participants
Number of Participants Experiencing SAEs, IMEs and/or Severe Local Reactions
ParticipantsGroup AGroup BGroup CGroup D
SAE10679
IME4022
SLR0000

Adverse events

Collected over 9 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Group A1/195 (0.5%)12/195 (6.2%)7/195 (3.6%)
Group B0/172 (0%)7/172 (4.1%)0/172 (0%)
Group C0/170 (0%)9/170 (5.3%)4/170 (2.4%)
Group D0/207 (0%)9/207 (4.3%)2/207 (1%)
Most frequent serious events
Showing 10 of 21
Most frequent serious events
EventGroup AGroup BGroup CGroup D
PneumoniaInfections and infestations1/1953/1724/1702/207
Amoebic dysenteryInfections and infestations0/1950/1722/1701/207
BronchiolitisInfections and infestations2/1950/1720/1702/207
Urinary Tract InfectionInfections and infestations2/1950/1720/1700/207
HydrocephalusNervous system disorders0/1950/1721/1700/207
Intracranial pressure increasedNervous system disorders0/1950/1721/1700/207
UrticariaSkin and subcutaneous tissue disorders0/1950/1721/1700/207
GastroenteritisInfections and infestations1/1951/1720/1700/207
Abscess limbInfections and infestations0/1951/1720/1700/207
Glucose-6-Phosphate Dehydrogenase DeficiencyCongenital, familial and genetic disorders0/1951/1720/1700/207
Most frequent other events
Most frequent other events
EventGroup AGroup BGroup CGroup D
BronchiolitisInfections and infestations3/1950/1720/1702/207
Febrile convulsionInfections and infestations2/1950/1721/1700/207
PharyngotonsillitisInfections and infestations0/1950/1721/1700/207
Cow milk intoleranceMetabolism and nutrition disorders1/1950/1721/1700/207
DiarrheaGastrointestinal disorders0/1950/1721/1700/207
CryptorchismCongenital, familial and genetic disorders1/1950/1720/1700/207

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Group AGroup BGroup CGroup DTotal
<=18 years200178178217773
Between 18 and 65 years00000
>=65 years00000
Sex: Female, Male
Sex: Female, Male(Participants)Group AGroup BGroup CGroup DTotal
Female939282105372
Male1078696112401
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Group AGroup BGroup CGroup DTotal
Black or African American417315
Hispanic105108101132446
Latin American88696878303
White / Caucasian30249
Region of Enrollment
Region of Enrollment(participants)Group AGroup BGroup CGroup DTotal
Panama1128293100387
Dominican Republic889685117386
07

Study locations

4 sites
  • Hospital Universitario Nuestra Señora de la Alta Gracia
    Santo Domingo, Dominican Republic
  • Cevaxin Vaccination Center
    David, Panama
  • Cevaxin Vaccination Center
    La Chorrera, Panama
  • Cevaxin Vaccination Center
    Panama city, Panama
08

References and documents

Publications

  • 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. PubMed 33284114 ↗

Study documents

  • Protocol and statistical analysis plan · Apr 12, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Undecided

09

Registry details

Key details

Study ID
NCT03239496
Lead sponsor
Fidec Corporation
Collaborators
Bill and Melinda Gates Foundation
Responsible party
Sponsor
First posted
Aug 4, 2017
Start date
Oct 23, 2017
Primary completion
Nov 13, 2018
Completion
Nov 13, 2018
Results posted
Aug 18, 2020
Last update
Jul 21, 2023

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Jul 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Poliomyelitis→

Other studies from this sponsor

Fidec Corporation

Start the discussion