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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Rotavirus

Intervention / Treatment
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* Biological: Squarekids
* Biological: Rotarix


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Co-administration Group<br>Subjects aged 6 to 12 weeks who receive the Squarekids vaccine (diphtheria, tetanus, pertussis and inactivated poliovirus [DPT-IPV] vaccine) according to a 3, 4, 6 month schedule and the liquid Rotarix vaccine (oral live attenuated human rotavirus [HRV] vaccine) according to a 2, 3 month schedule. The HRV vaccine is administered orally while the DTP-IPV vaccine is administered subcutaneously in the upper arm or upper thigh. | Biological: Squarekids<br>* Three doses administered subcutaneously in the upper arm or thigh<br>Biological: Rotarix<br>* Two doses administered orally<br>|
| Active Comparator: Staggered Group<br>Subjects aged 6 to 12 weeks who receive the Squarekids vaccine (diphtheria, tetanus, pertussis and inactivated poliovirus [DPT-IPV] vaccine) according to a 3, 4.5, 6 month schedule and the liquid Rotarix vaccine (oral live attenuated human rotavirus [HRV] vaccine) according to a 2, 3.5 month schedule. The HRV vaccine is administered orally while the DTP-IPV vaccine is administered subcutaneously in the upper arm or upper thigh. | Biological: Squarekids<br>* Three doses administered subcutaneously in the upper arm or thigh<br>Biological: Rotarix<br>* Two doses administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Anti-diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations Greater Than or Equal to (≥) the Cut-off Value | Percentage of subjects with anti-D and anti-T antibody concentrations ≥ 0.1 international units per milliliter (IU/mL). | One month post third dose of DTP-IPV vaccine (At Month 5) | 
| Percentage of Subjects With Anti-pertussis Toxoid (Anti-PT) and Anti-filamentous Haemagglutinin (Anti-FHA) Antibody Concentrations ≥ the Cut-off Value | Percentage of subjects with anti-PT and anti-FHA antibody concentrations ≥ 10 IU/mL. | One month post third dose of DTP-IPV vaccine (At Month 5) | 
| Percentage of Subjects With Anti-poliovirus Serotypes 1, 2 and 3 (Anti-polio 1, 2 and 3) Antibody Titers ≥ the Cut-off Value | Percentage of subjects with anti-polio 1, 2 and 3 antibody titers ≥ 8 estimated doses 50% (ED50). | One month post third dose of DTP-IPV vaccine (At Month 5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Seropositive Subjects for Serum Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies in a Sub-cohort of Subjects | A seropositive subject for serum anti-RV IgA antibodies was defined as a subject with anti-RV IgA antibody concentration ≥ the seropositivity cut-off value of 20 units per milliliter (U/mL). Immunogenicity of the liquid HRV vaccine in terms of serum anti-RV IgA antibody seropositivity was assessed in a sub-cohort of subjects (HRV immunogenicity sub-cohort) which included the first 73 subjects enrolled into each of the 2 study groups. | 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) | 
| Serum Anti-RV IgA Antibody Concentration to Evaluate Immunogenicity in a Sub-cohort of Subjects | Concentration of serum anti-RV IgA antibody was assessed by Enzyme Linked Immunosorbent Assay (ELISA) and expressed as geometric mean concentration (GMC) in U/mL. The assay cut-off was 20 U/mL. Immunogenicity of the liquid HRV vaccine in terms of serum anti-RV IgA antibody GMC was assessed in a sub-cohort of subjects (HRV immunogenicity sub-cohort) which included the first 73 subjects enrolled into each of the 2 study groups. | 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) | 
| Anti-D and Anti-T Antibody Concentrations to Evaluate Immunogenicity | Concentrations of anti-D and anti-T antibodies were assessed by ELISA, presented as GMCs and expressed in IU/mL. The assay cut-off for anti-D and anti-T antibody concentrations was 0.1 IU/mL. | One month post third dose of DTP-IPV vaccine (At Month 5) | 
| Anti-polio 1, 2 and 3 Antibodies Titers to Evaluate Immunogenicity | Titers of anti-polio 1, 2 and 3 were assessed by Neutralisation Assay (NEU) and presented as Geometric Mean Titers (GMTs). The assay cut-off was 8 ED50. | One month post third dose of DTP-IPV vaccine (At Month 5) | 
| Anti-PT and Anti-FHA Antibody Concentrations to Evaluate Immunogenicity | Concentrations of anti-PT and anti-FHA antibodies were assessed by ELISA, presented as GMCs and expressed in IU/mL. The assay cut-offs for anti-PT and anti-FHA antibody concentrations were 2.693 IU/mL and 2.046 IU/mL respectively. | One month post third dose of DTP-IPV vaccine (At Month 5) | 
| Number of Subjects With Any Solicited General Adverse Events (AEs) After Each Dose of Liquid HRV Vaccine | Assessed solicited general AEs were fever (defined as axillary temperature ≥ 37.5 degrees Celsius [°C]), irritability/fussiness, diarrhoea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥ 1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 8-day (Days 0-7) follow-up period after each dose of liquid HRV vaccine | 
| Number of Subjects With Any Solicited Local AEs After First Dose of DTP-IPV Vaccine | Assessed solicited local AEs were pain, redness and swelling at injection site. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 8-day (Days 0-7) follow-up period after first dose of DTP-IPV vaccine | 
| Number of Subjects With Any Solicited General AEs After First Dose of DTP-IPV Vaccine | Assessed solicited general AEs were drowsiness, fever (defined as axillary temperature ≥ 37.5 °C), irritability/fussiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 8-day (Days 0-7) follow-up period after first dose of DTP-IPV vaccine | 
| Number of Subjects With Any Unsolicited AEs After Each Dose of Liquid HRV Vaccine | Unsolicited AEs were defined as any AE reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) follow-up period after each dose of liquid HRV vaccine | 
| Number of Subjects With Any Unsolicited AE After First Dose of DTP-IPV Vaccine | Unsolicited AEs were defined as any AE reported in addition to those solicited during the clinical study and any solicited AE with onset outside the specified period of follow-up for solicited AEs. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the 31-day (Days 0-30) follow-up period after first dose of DTP-IPV vaccine | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | Assessed SAEs included any untoward medical occurrence that resulted in death, was life threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. | During the entire study period (from Day 0 to Month 5) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diphtheria, Tetanus, Pertussis and Inactivated Poliovirus (DPT-IPV) vaccine, Oral HRV liquid vaccine, Immunogenicity, Healthy Japanese infants, Safety, Vaccination