Clinical trial NCT02907216: Evaluation of Immunogenicity and Safety of the Diphtheria, Tetanus, Pertussis and Inactivated Poliovirus (DPT-IPV) Vaccine Squarekids Co-administered With GSK Biologicals' Human Rotavirus (HRV) Vaccine Rotarix (GSK444563) in Healthy Infants
Official title: Immunogenicity and Safety of the Diphtheria, Tetanus, Pertussis and Inactivated Poliovirus (DPT-IPV) Vaccine Squarekids Co-administered With GSK Biologicals' Human Rotavirus (HRV) Vaccine Rotarix (GSK444563) in Healthy Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Rotavirus
Keywords: Healthy Japanese infants
Safety
Diphtheria, Tetanus, Pertussis and Inactivated Poliovirus (DPT-IPV) vaccine
Vaccination
Oral HRV liquid vaccine
Immunogenicity
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-09-20
Enrollment: 292
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the immunogenicity and safety of the diphtheria, tetanus, pertussis and inactivated poliovirus (DPT-IPV) vaccine Squarekids administered with or without the GSK Biologicals' liquid Rotarix (HRV) vaccine, in healthy Japanese infants aged 6 - 12 weeks. GSK Biologicals' liquid HRV vaccine Rotarix is licensed in Japan since 2011. Although the concomitant administration of GSK Biologicals' DTP-IPV vaccine has been evaluated during the clinical development of the HRV vaccine, the vaccine differed in composition and route of administration from the DPT-IPV vaccine Squarekids manufactured in Japan. Hence, as requested by the Japanese regulatory authorities, this post-licensure study will evaluate the immunogenicity of the DPT-IPV vaccine manufactured in Japan when co-administered with the liquid HRV vaccine

Detailed description: This study is a phase IV, open-label, randomised, controlled, multi-centric, single-country study with two parallel groups. Subjects in the co-administration group will be administered the DPT-IPV vaccine according to a 3, 4, 6 month schedule and the liquid HRV vaccine according to a 2, 3 month schedule. Subjects in the staggered group will be administered the DPT-IPV vaccine according to a 3, 4.5, 6 month schedule and the liquid HRV vaccine according to a 2, 3.5 month schedule. The intended duration of the study, per subject, is 5 months.

A sub-cohort of subjects (HRV Immunogenicity sub-cohort) from both the study groups will include the first 73 subjects enrolled into the study to assess the serum anti-RV IgA seropositivity and Geometric Mean Concentrations (GMC).

Eligibility criteria: Inclusion Criteria:

* Subjects' parent(s)/ Legally Acceptable Representative(s) \[LAR(s)\] who, in the opinion of the investigator can and will comply with the requirements of the protocol.
* A male or female between, and including, 6 and 12 weeks of age at the time of the first dose of HRV vaccination.
* Written informed consent obtained from the parent(s)/LAR(s) of the subject prior to performing any study specific procedure.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Born full-term as per the delivery records.

Exclusion Criteria:

* Child in care.
* Use of any investigational or non-registered product other than the study vaccines within 30 days before the first dose of study vaccine, or planned use during the study period.
* Chronic administration of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, this will mean prednisone (≥ 0.5 mg/kg/day, or equivalent). Inhaled and topical steroids are allowed.
* Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
* Administration of long-acting immune-modifying drugs at any time during the study period.
* Planned administration/administration of a vaccine not fore-seen by the study protocol within the period starting 30 days before the first dose of HRV vaccine administration and ending at Visit 7, with the exception of other routinely administered vaccines like PCV, Hib, BCG, hepatitis B, meningococcal vaccine and inactivated influenza vaccines, which are allowed at any time during the study, if administered at sites different from the sites used to administer the DPT-IPV vaccine.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Uncorrected congenital malformation of the gastrointestinal tract that would predispose for Intussusception (IS).
* History of IS.
* Family history of congenital or hereditary immunodeficiency.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Major congenital defects or serious chronic illness.
* Previous vaccination against rotavirus, diphtheria, tetanus, pertussis and/ or poliovirus.
* Previous confirmed occurrence of RV GE, diphtheria, tetanus, pertussis, and/ or polio disease.
* GE within 7 days preceding the HRV vaccine administration.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the HRV or DPT-IPV vaccines.
* Hypersensitivity to latex.
* History of any neurological disorders or seizures.
* History of SCID.
* Acute disease and/or fever at the time of enrollment.

  * Fever is defined as temperature ≥ 37.5°C /99.5°F on oral, axillary or tympanic setting, or ≥ 38.0°C /100.4°F on rectal setting.
  * Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.

Primary outcomes:
measure: Percentage of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Greater Than or Equal to (≥) the Cut-off Value
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
measure: Percentage of Subjects With Anti-pertussis Toxoid (Anti-PT) and Anti-filamentous Haemagglutinin (Anti-FHA) Antibody Concentrations ≥ the Cut-off Value
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
measure: Percentage of Subjects With Anti-poliovirus Serotypes 1, 2 and 3 (Anti-polio 1, 2 and 3) Antibody Titers ≥ the Cut-off Value
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
Secondary outcomes:
measure: Percentage of Seropositive Subjects for Serum Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies in a Sub-cohort of Subjects
timeFrame: One month post second dose of liquid HRV vaccine (At Month 2 for the Co-administration Group and at Month 2.5 for the Staggered Group)
measure: Serum Anti-RV IgA Antibody Concentration to Evaluate Immunogenicity in a Sub-cohort of Subjects
timeFrame: One month post second dose of liquid HRV vaccine (At Month 2 for the Co-administration Group and at Month 2.5 for the Staggered Group)
measure: Anti-D and Anti-T Antibody Concentrations to Evaluate Immunogenicity
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
measure: Anti-polio 1, 2 and 3 Antibodies Titers to Evaluate Immunogenicity
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
measure: Anti-PT and Anti-FHA Antibody Concentrations to Evaluate Immunogenicity
timeFrame: One month post third dose of DTP-IPV vaccine (At Month 5)
measure: Number of Subjects With Any Solicited General Adverse Events (AEs) After Each Dose of Liquid HRV Vaccine
timeFrame: During the 8-day (Days 0-7) follow-up period after each dose of liquid HRV vaccine
measure: Number of Subjects With Any Solicited Local AEs After First Dose of DTP-IPV Vaccine
timeFrame: During the 8-day (Days 0-7) follow-up period after first dose of DTP-IPV vaccine
measure: Number of Subjects With Any Solicited General AEs After First Dose of DTP-IPV Vaccine
timeFrame: During the 8-day (Days 0-7) follow-up period after first dose of DTP-IPV vaccine
measure: Number of Subjects With Any Unsolicited AEs After Each Dose of Liquid HRV Vaccine
timeFrame: During the 31-day (Days 0-30) follow-up period after each dose of liquid HRV vaccine
measure: Number of Subjects With Any Unsolicited AE After First Dose of DTP-IPV Vaccine
timeFrame: During the 31-day (Days 0-30) follow-up period after first dose of DTP-IPV vaccine
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: During the entire study period (from Day 0 to Month 5)
Other outcomes:
Locations:
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Gillard P, Tamura T, Kuroki H, Morikawa Y, Moerman L, Parra J, Kitamura Y, Mihara K, Okamasa A. Immunogenicity and safety of the diphtheria, pertussis, tetanus and inactivated poliovirus vaccine when co-administered with the human rotavirus vaccine (Rotarix) in healthy Japanese infants: a phase IV randomized study. Hum Vaccin Immunother. 2019;15(4):800-808. doi: 10.1080/21645515.2018.1564441. Epub 2019 Feb 20.