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Trial registered on ANZCTR


Registration number
ACTRN12623001320640p
Ethics application status
Submitted, not yet approved
Date submitted
23/06/2023
Date registered
15/12/2023
Date last updated
15/12/2023
Date data sharing statement initially provided
15/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Inactivated Poliovirus Vaccine (IPV) on Mucosal Immunity: A Randomized, Controlled Trial in Cuba
Scientific title
Impact of IPV on mucosal immunity: A randomized controlled trial comparing nasopharyngeal and intestinal poliovirus shedding after bOPV challenge in IPV recipients with those not receiving IPV
Secondary ID [1] 309969 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Poliomyelitis 330459 0
Condition category
Condition code
Infection 327310 327310 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a two-armed study with an interventional (A) and a control arm (B). The intervention arm A will receive one full dose of Inactivated Poliovirus Vaccine (IPV) administered via intramuscular injection.
- IPV contents: 40 D antigen units of Type 1, 8 D antigen units of Type 2, and 32 D antigen units of Type 3 poliovirus.
- IPV Dose: 0.5 mL (full dose)
- Who will administer: local medical clinic nurse
- Where: at the local medical clinic
- When: between 6-8 months of age

All participants will receive the usual polio vaccines administered via routine immunization and national immunization days in Cuba (i.e., fractional-dose IPV administered intradermally at 4 and 8 months, one dose of bivalent oral poliovirus vaccine (bOPV) in the national immunization days). However, as a result of this study, administration of the second dose of fIPV will be delayed by 1 month.
- fIPV contents: IPV contents: 40 D antigen units of Type 1, 8 D antigen units of Type 2, and 32 D antigen units of Type 3 poliovirus.
- fIPV Dose: 0.1 mL (fractional dose)
Intervention code [1] 326383 0
Treatment: Drugs
Comparator / control treatment
Control group receives no dose of inactivated poliovirus vaccine (IPV).

Participants in the control group will receive no intervention during the study. They will receive the usual polio vaccines administered via routine immunization and national immunization days in Cuba (i.e., fractional-dose IPV administered intradermally at 4 and 8 months, one dose of bOPV in the national immunization days). However, as a result of this study administration the second dose of fIPV will be delayed by 1 month.
- fIPV contents: IPV contents: 40 D antigen units of Type 1, 8 D antigen units of Type 2, and 32 D antigen units of Type 3 poliovirus.
- fIPV Dose: 0.1 mL (fractional dose)
Control group
Active

Outcomes
Primary outcome [1] 335171 0
Difference in proportion (expressed as percentage) of nasopharyngeal shedding of poliovirus serotypes 1 and 3 (as a composite outcome) between arms A (interventional: full dose IPV) and B (control: no IPV). This data is generated through a cotton nasal/oral swab and analyzed via PCR.
Timepoint [1] 335171 0
at 7- and 28-days post bOPV (1 month and 1 week post intervention, and 2 months post intervention).
Primary outcome [2] 335468 0
Difference in proportion (expressed as percentage) of mucosal shedding of poliovirus serotypes 1 and 3 (as a composite outcome) between arms A (interventional: full dose IPV) and B (control: no IPV). This data is generated through a stool sample and analyzed via viral isolation in cell cultures (L20B and RD).
Timepoint [2] 335468 0
at 7- and 28-days post bOPV (1 month and 1 week post intervention, and 2 months post intervention).
Secondary outcome [1] 423386 0
Seroconversion for all three serotypes (as a composite outcome) in Arm A (Internventional: full dose IPV) and Arm B (control: no IPV). Participant data is collected as blood sample.
Timepoint [1] 423386 0
4 and 8 weeks after interventional administration. 4 weeks after bOPV (2 months after intervention)
Secondary outcome [2] 423387 0
Seroprevalence at the final visit of all three serotypes (as a composite outcome) by study arm. Seropositivity defined as log2 antibody titres >3. Participant data is collected as blood sample.
Timepoint [2] 423387 0
8 weeks after enrollment (IPV administration in Arm A)
Secondary outcome [3] 423388 0
Median titers of all three serotypes by study arm (as a composite outcome). Participant data is collected as blood sample.
Timepoint [3] 423388 0
4 and 8 weeks after enrollment (Arm A IPV administration at enrollment, bOPV challenge 1 month after enrollment).

Eligibility
Key inclusion criteria
1. Healthy infants born June-August 2023 (i.e, 6-8 months of age at time of enrolment in February 2024) residing in Camaguey province of Cuba
2. Over the 3rd percentile for height and weight
3. Resident of the study locality for more than or at least 5 months, with no plans to move
4. Previously received one dose of fIPV in primary series at 4 months of age
5. Parent/guardian consent for participation in the study and for samples collection
Minimum age
6 Months
Maximum age
8 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Infant not fulfilling inclusion criteria
2. Contraindication for venepuncture
3. Having received bOPV or 2nd fIPV dose before enrolment
4. Acutely sick child or child requiring hospitalization. These children will be referred to the nearest medical facility equipped to handle the case at their own expense.
5. Diagnosis or suspicion in the subject or an immediate family member of congenital medical conditions (e.g., Down Syndrome); primary immunodeficiency disorder; chronic medical illness (e.g., renal, cardiac)
6. Infants of mothers below the legal age (<18 years) or with mental incapacity will not be eligible to participate.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
"Allocation is not concealed"
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomization of sizes 2, 4 and 6 will be applied to produce the random sequence. The random sequence with serial number will be handed to the principal investigator. The parent or the study investigator had no discretion to opt for a particular study arm. The randomly allocated sequence will be handed over to the vaccine administrator who will check the sequence and administer the study vaccine as mentioned in the sequence.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
This study is open-labeled because the participants and the study investigators are not masked to the vaccines administered. However, the laboratory investigators at the PKI, who will be the outcome assessors, will be masked to the study arm allocation.
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
8/01/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
400
Accrual to date
Final
Recruitment outside Australia
Country [1] 25606 0
Cuba
State/province [1] 25606 0
Camagüey Province

Funding & Sponsors
Funding source category [1] 314144 0
Government body
Name [1] 314144 0
World Health Organization
Country [1] 314144 0
Switzerland
Funding source category [2] 314146 0
Government body
Name [2] 314146 0
Ministry of Health, Cuba
Country [2] 314146 0
Cuba
Primary sponsor type
Government body
Name
World Health Organization
Address
WHO Headquarters
Avenue Appia 20
1211
Geneva 27
Country
Switzerland
Secondary sponsor category [1] 316063 0
Other Collaborative groups
Name [1] 316063 0
Pedro Kouri Institute
Address [1] 316063 0
Autopista Novia del Mediodía, KM 6 1/2, La Lisa, La Habana, 11400,
Country [1] 316063 0
Cuba

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313279 0
Research Ethics Review Committee (WHO ERC)
Ethics committee address [1] 313279 0
Av. Appia 20, 1202 Genève, Switzerland
Ethics committee country [1] 313279 0
Switzerland
Date submitted for ethics approval [1] 313279 0
12/05/2023
Approval date [1] 313279 0
Ethics approval number [1] 313279 0
Ethics committee name [2] 313281 0
CEI-IPK
Ethics committee address [2] 313281 0
2GPF+66V, La Habana, Cuba
Ethics committee country [2] 313281 0
Cuba
Date submitted for ethics approval [2] 313281 0
17/04/2023
Approval date [2] 313281 0
Ethics approval number [2] 313281 0

Summary
Brief summary
The current World Health Organization (WHO) outbreak response guidelines recommend use of oral poliovirus vaccines (OPVs) to interrupt transmission of poliovirus outbreaks due to their ability to induce intestinal mucosal immunity. However, countries that exclusively use inactivated poliovirus vaccine (IPV) in their immunization schedules may be reluctant to reintroduction of OPV as it poses hurdles in both regulatory aspects and carries risk of seeding of vaccine-derived polioviruses (VDPVs). Additionally, the use of exclusive IPV was able to eliminate wild poliovirus in settings with higher sanitation and hygiene levels where oral-oral transmission dominates, likely through the induction of nasopharyngeal immunity.

There is a limited number of studies that analyse nasopharyngeal mucosal immunity related to IPV: 4 interventional studies and 1 observational study during an outbreak in the USA. Furthermore, the studies have many limitations including undetectable virus in nasopharyngeal washings, interference with natural exposure to poliovirus and small sample sizes. Following a literature review conducted on the impact of IPV on mucosal immunity, the SAGE Polio Working Group recommended that a clinical trial is conducted to generate evidence on the impact of IPV on nasopharyngeal shedding, which can inform policy on the use of IPV-only outbreak responses in settings where oral-oral transmission dominates.

Cuba provides a unique setting in which to evaluate the serological immunity because of the absence of wild polioviruses since 1962 and its unique strategy for administering OPV in annual campaigns. Poliomyelitis was eliminated from Cuba in the early 1960s. Since then, OPV has been administered to children through biannual NIDs. Each NID round lasts approximately one week during February and May, targeting all children aged greater than one month and less than 3 years with two doses of bOPV. OPV is not available at any other time of the year. In addition, previous studies in Cuba have shown that the attenuated Sabin virus contained in OPV disappears rapidly from the population after the second round of NIDs. For these reasons, the potential for “contamination” of the study arms by circulating OPV-like strains is minimized if not eliminated.

Cuba was selected as study country because it is the only country in the world that satisfies two conditions: 1) OPV is administered exclusively in annual campaigns (leaving approximately 7 months of OPV-free environment) and 2) IPV is administered at 14 weeks of age but may be delayed up to 4 months of age. This fits well with the design of the study which seeks to understand viral shedding after poliovirus exposure (through an OPV challenge dose) in IPV-vaccinated children. Cuba is using fractional IPV administered intradermally at 4 and 8 months of age in their routine immunisation (RI) program.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 127582 0
Prof Sonia Resik
Address 127582 0
Tropical Medicine Institute Pedro Kourí
2GPF+66V, La Habana, Cuba
Country 127582 0
Cuba
Phone 127582 0
+537 2553550
Fax 127582 0
Email 127582 0
[email protected]
Contact person for public queries
Name 127583 0
Prof Sonia Resik
Address 127583 0
Tropical Medicine Institute Pedro Kourí
2GPF+66V, La Habana, Cuba
Country 127583 0
Cuba
Phone 127583 0
+537 2553550
Fax 127583 0
Email 127583 0
[email protected]
Contact person for scientific queries
Name 127584 0
Prof Sonia Resik
Address 127584 0
Tropical Medicine Institute Pedro Kourí
2GPF+66V, La Habana, Cuba
Country 127584 0
Cuba
Phone 127584 0
+537 2553550
Fax 127584 0
Email 127584 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All the names and personal information regarding any individual will be kept confidential and data sets will be kept anonymous for analysis. Identifying data will not be used in any publications, reports, or media, in any manner which could identify an individual participant. Individual data of published results only can be made available upon request.
When will data be available (start and end dates)?
After last study follow-ups (estimated May 2024) study data will be available. Data will then be securely stored for 3 years at IPK (estimated end date May 2027) - only accessible by the Principal Investigator, Dr. Sonia Resik.
Available to whom?
individual data of published results only can be made publicly available upon request.
Available for what types of analyses?
Statistical analyses (meta-analyses, seroprevalence, percent shedding, median titres, statistical significance, risk analysis, sociodemographic variables, etc)
How or where can data be obtained?
Data can be made available upon request by emailing the principal investigator Dr. Sonia Resik ([email protected]).


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19527Study protocol  [email protected]
19528Informed consent form  [email protected]
19529Ethical approval  [email protected]
19530Data dictionary  [email protected]



Results publications and other study-related documents

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