Clinical trial NCT03025750: Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine in 2, 4, 6 Months of Age
Official title: Safety and Immunogenicity of Adjuvanted Reduced Dose Inactivated Polio Vaccine, IPV-Al SSI, in Comparison to Non-adjuvanted Full Dose IPV SSI, in Infants Vaccinated at 2, 4 and 6 Months of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Poliomyelitis
Lead sponsor: Statens Serum Institut
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
name: Larix A/S
name: Vaxtrials S.A.
name: AJ Vaccines A/S
First posted: 2017-01-19
Enrollment: 800
Sex: ALL
Minimum age (years): 54
Maximum age (years): 75
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The trial is a phase III, non-inferiority, observer-blind, randomised, active controlled, multicentre clinical trial with 2 parallel groups: IPV-Al SSI (investigational vaccine) and IPV SSI (comparator vaccine). The vaccines will be administered at 2, 4 and 6 months of age.

Detailed description: In addition to the trial vaccines (IPV-Al SSI or IPV SSI), the trial subjects will receive concomitant childhood vaccinations during the trial period. The trial vaccine (IPV-Al SSI or IPV SSI) is administered in the RIGHT thigh, whereas the other injectable childhood vaccines are administered in the opposite (LEFT) thigh.

At Visit 1 (inclusion, screening, blood sample, randomisation and 1st vaccination), written informed consent is obtained and the subject's eligibility is assessed according to the pre-specified in-/exclusion criteria. Information on medical history, demographics and concomitant medication are collected and a physical examination is performed and vital signs are measured. A prevaccination blood sample is taken for polio antibody determinations and the subject is randomly allocated into one of the two vaccination groups and vaccinated. A subset of 200 subjects are randomly chosen to have an extra blood sample taken at Visit 3. The subject is observed for immediate AEs 30 minutes after all vaccinations. An eDiary, thermometer and ruler are handed out to the parents for measurements of temperature and recording of injection site reactions and solicited systemic AEs. These activities are performed daily, starting on the day of the vaccination and the following 2 days and until resolved, and for recording of any other AEs as instructed by the trial staff. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary.

At Visit 2 (2nd vaccination), 2 months after Visit 1, the eDiary is collected and AEs and concomitant medications are recorded. Contraindications are reviewed, the 2nd vaccination is administered, immediate reactions are observed and the eDiary is returned to the partents for recordings of AEs and concomitant medications. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary.

At Visit 3 (3rd vaccination), 2 months after Visit 2, the eDiary is collected and AEs and concomitant medication are recorded. A blood sample from a subset of the subjects is taken for polio antibody determinations. Contraindications are reviewed, the 3rd vaccination is given, immediate reactions are observed and the eDiary is returned to the parents. A contact to the parents via telephone will be made after the vaccination visit to remind the parents to fill in the eDiary and to check if they have any questions regarding how use the eDiary.

At Visit 4 (blood sample and trial completion), 1 month after Visit 3, the eDiary is collected and AEs and concomitant medications are recorded and a blood sample for polio antibody determination is taken.

A safety follow-up telephone call will be conducted at 12 months of age.

Eligibility criteria: Inclusion Criteria:

* Infants 2 months of age (54-75 days of age) on date of first vaccination
* Healthy assessed from medical history and physical examination
* Parent(s)/guardian(s) have been properly informed about the trial and signed informed consent form
* Parent(s)/guardian(s)granted access to the infant's trial related medical records
* Parent(s)/guardian(s)are likely to comply with trial procedures

Exclusion Criteria:

* Vaccinated with any polio vaccine other than the trial vaccines, prior to inclusion or planned during the trial
* OPV vaccination or known exposure to poliovirus (wild or vaccine-derived) in household (living together) within 3 months prior to inclusion or planned during the trial
* Low birth weight (\< 2,500 g)
* Known or suspected immunodeficiency (e.g. leukaemia, lymphoma) or family history of congenital or hereditary immunodeficiency. HIV infection is not an exclusion criteria
* Severe uncontrolled chronic (e.g. neurologic, pulmonary, gastrointestinal, hepatic, renal or endocrine) disease
* Known or suspected allergy to vaccine constituents (e.g. hypersensitivity to formaldehyde, aluminium or 2-phenoxyethanol)
* Uncontrolled coagulopathy or blood disorder contraindicating intramuscular injections or blood sampling
* Treatment with a product which is likely to modify the immune response (e.g. systemic corticosteroids, blood products and immunoglobulins) prior to inclusion or planned during the trial period
* Participating in another clinical trial
* Not suitable for inclusion in the opinion of the investigator

Primary outcomes:
measure: Seroconversion for poliovirus type 1, 2 and 3 for IPV-Al compared to IPV SSI in infants
timeFrame: Change from baseline to one month after 3rd vaccination
Secondary outcomes:
measure: Adverse events following vaccinations (key secondary)
timeFrame: After primary injections at 2, 4 and 6 months of age
measure: Subjects with seroprotection against poliovirus types 1, 2 and 3
timeFrame: One months after 3rd vaccination
measure: Subjects with poliovirus types 1, 2 and 3 post-vaccination titres >= 4-fold above estimated titre of maternal antibody
timeFrame: One months after 3rd vaccination
measure: Geometric mean titres (GMTs) and median titers for poliovirus types 1, 2 and 3
timeFrame: One months after 3rd vaccination
measure: Reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3
timeFrame: From baseline and one months after 3rd vaccination
Other outcomes:
measure: Subject with seroconversion against poliovirus types 1, 2 and 3
timeFrame: Two months after 2nd vaccination
measure: Subjects with seroprotection against poliovirus types 1, 2 and 3
timeFrame: Two months after 2nd vaccination
measure: Subjects with poliovirus types 1, 2 and 3 post-vaccination titres ≥ 4-fold above estimated titre of maternal antibody
timeFrame: Two months after 2nd vaccination
measure: Geometric mean titres (GMTs) and median titers for poliovirus types 1, 2 and 3
timeFrame: Two months after 2nd vaccination
measure: Reverse cumulative titre distribution curves for poliovirus types 1, 2 and 3
timeFrame: From baseline and two months after 2nd vaccination
measure: Sensitivity analysis: subjects with ≥ 4-fold increases in poliovirus types 1, 2 and 3 titres
timeFrame: From baseline and one months after 3rd vaccination
measure: Sensitivity analysis: sub-groups of subjects with seroprotection (titre ≥ 8) and without seroprotection (titre < 8) at baseline
timeFrame: One months after 3rd vaccination
Locations:
city: Panama City
country: Panama
facility: Cevaxin
Study officials:
affiliation: Statens Serum Institut
name: Ingrid Kromann
role: STUDY_DIRECTOR
References:
citation: Saez-Llorens X, Thierry-Carstensen B, Stoey LS, Sorensen C, Wachmann H, Bandyopadhyay AS, Nielsen PI, Kusk MV. Immunogenicity and safety of an adjuvanted inactivated polio vaccine, IPV-Al, following vaccination in children at 2, 4, 6 and at 15-18 months. Vaccine. 2020 May 6;38(21):3780-3789. doi: 10.1016/j.vaccine.2020.02.066. Epub 2020 Apr 6.