Clinical trial NCT02914184: Evaluation of Immunogenicity and Safety of Two Formulations of GSK Biologicals' Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks
Official title: Immunogenicity and Safety Study of Two Formulations of GlaxoSmithKline (GSK) Biologicals' Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Rotavirus
Rotavirus Vaccines
Keywords: Safety
Healthy infants
Immunogenicity
Human Rotavirus (HRV)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2016-09-26
Enrollment: 1612
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 clinical consistency of three production lots of the Porcine circovirus (PCV)-free liquid formulation of oral live attenuated human rotavirus (HRV) vaccine and to evaluate the PCV-free liquid formulation of HRV vaccine as compared to the currently licensed lyophilised formulation of the HRV vaccine in terms of immunogenicity, reactogenicity and safety when administered as a two-dose vaccination in healthy infants starting at age 6-12 weeks. No new subjects will be enrolled in the extension phase of the study.

Detailed description: * Experimental design: Phase IIIA, observer-blind, randomised (1:1:1:1), controlled, multi-centric, with four parallel groups and a staggered enrolment (Part A and Part B).
* Duration of the study: The intended duration of the study, per subject, will be approximately 7-8 months including the 6 months of extended safety follow-up period after the last dose of HRV vaccine.

  * Epoch 001: Primary starting at Visit 1 (Day 0) and ending at the safety follow-up contact (Month 7-8).
* Primary completion Date (PCD): Visit 3 (Month 2-4).
* End of Study (EoS): Last testing results released of samples collected at Visit 3 or Last Subject Last Visit (LSLV) (Follow up contact at month 7-8).
* Study Groups:

  * PCV-free HRV liquid formulation lot A (also referred to as Liq_A Group)
  * PCV-free HRV liquid formulation lot B (also referred to as Liq_B Group)
  * PCV-free HRV liquid formulation lot C (also referred to as Liq_C Group)
  * GSK Biologicals' currently licensed lyophilised HRV formulation (also referred to as Lyo Group)
* Control:active control-GSK Biologicals' currently licensed lyophilised HRV vaccine
* Vaccination schedule: Two doses of HRV vaccine to be administered according to a 0, 1-2 month schedule according to the immunisation schedule for RV vaccine.

Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by "Day n+1". Thus, the time frames (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.

Eligibility criteria: Inclusion Criteria:

* Subjects' parent(s)/LAR(s) who, in the opinion of the investigator can and will comply with the requirements of the protocol.
* Written informed consent obtained from the parent(s)/LAR(s) (Legally acceptable representatives) of the subject prior to performing any study specific procedure.
* A male or female infant between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first study vaccination.
* Born full-term (i.e., between a gestation period of 37 weeks 0 days and 41 weeks 6 days).
* Healthy subjects as established by medical history and clinical examination before entering into the study.

Exclusion Criteria:

* Child in care
* Use of any investigational or non-registered product other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day-29 to Day 0), 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 foreseen by the study protocol in the period starting 30 days before the first dose of vaccine administration and ending at Visit 3, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study and other licensed routine childhood vaccinations.
* 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 RV.
* Previous confirmed occurrence of RVGE.
* GE within 7 days preceding the study vaccine administration.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
* Hypersensitivity to latex.
* Acute disease and/or fever at the time of enrolment.

  * Fever is defined as temperature ≥38.0°C/100.4°F. The preferred location for measuring temperature in this study will be the oral cavity, the axilla and the rectum.
  * Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.

Primary outcomes:
measure: Anti-Rota Virus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations in the Human Rotavirus (HRV) Liquid Formulation Groups (Liq_A, Liq_B and Liq_C)
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to Cut-off Value in Porcine Circovirus (PCV) -Free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Control Group
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Percentage of Seroconverted Subjects With RV Antibody Concentrations Above or Equal to 20 U/mL in Porcine Circovirus (PCV)-Free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Pooled HRV Liquid Group) and Lyophilised Control Group
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Anti-RV IgA Antibody Concentrations in the PCV-free Liquid HRV Vaccine (Individual HRV Liquid Groups) and Lyophilised Control Group
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
Secondary outcomes:
measure: Percentage of Subjects With Anti-RV IgA Concentrations (Pooled HRV Liquid Group)
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Percentage of Subjects With Anti-RV IgA Concentrations (Individual HRV Liquid Groups)
timeFrame: At Month 2-4 (i.e. approximately 1-month or 2-months after second dose of HRV vaccine according to the immunisation schedule for RV vaccine administration in participating countries)
measure: Number of Subjects With Any Solicited General Adverse Events (AEs).
timeFrame: During the 8 days (Day 1 to Day 8) follow-up period after each dose of HRV vaccine
measure: Number of Subjects With Any Unsolicited AEs.
timeFrame: During the 31 day (Day 1 to Day 31) follow-up period after HRV vaccination across doses
measure: Number of Subjects With Any Serious Adverse Events (SAEs)
timeFrame: During the entire study period (Day 1 to Month 7-8)
Other outcomes:
Locations:
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city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
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city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Tauberbischofsheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Schoenau Am Koenigssee
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Frankenthal
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Bramsche
country: Germany
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
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city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
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city: Tokyo
country: Japan
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city: Tokyo
country: Japan
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city: Tokyo
country: Japan
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city: Gangwon-do
country: Korea, Republic of
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city: Gyeonggido
country: Korea, Republic of
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city: Incheon
country: Korea, Republic of
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city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
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country: Korea, Republic of
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city: Malaga
country: Spain
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state: Andalucia
city: Antequera/Málaga
country: Spain
facility: GSK Investigational Site
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country: Spain
facility: GSK Investigational Site
city: Castellón
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Marbella
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Hsinchu
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taichung
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taipei
country: Taiwan
facility: GSK Investigational Site
city: Taoyuan
country: Taiwan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Salamanca de la Cueva I, Pahud B, Huang LM, Leonardi M, Garcia-Sicilia J, Cespedes J, Abdelnour A, Tamura T, Kuroki H, Chiu NC, Virta M, Kokko S, Horn M, Panzer F, Kim JH, Jin L, Moerman L, Debacq C, Parra J, Ugarte A, Bi D; Rota-081 Study Group. Immunogenicity and safety of porcine circovirus-free human rotavirus vaccine in healthy infants: a phase III, randomized trial. J Infect Dis. 2020 May 4;225(12):2106-15. doi: 10.1093/infdis/jiaa210. Online ahead of print.