Safety Study of 2 Formulations of GSK's Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks

A Phase III, Observer-blind, Randomized, Multi-country Study to Assess the Reactogenicity and Safety of the Porcine Circovirus (PCV) Free Liquid Formulation of GSK's Oral Live Attenuated Human Rotavirus (HRV) Vaccine as Compared to the Lyophilized Formulation of the GSK's HRV Vaccine, When Administered as a 2-dose Vaccination in Infants Starting at Age 6-12 Weeks

The purpose of this study is to complete the total safety database size for GlaxoSmithKline Biologicals' (GSK's) human rotavirus (HRV) vaccine across the Porcine circovirus (PCV)-free development plan.

This study used a purposely selected lot for PCV-free liquid HRV vaccine that is in the upper range of the usual release potencies. The PCV-free liquid HRV vaccine lots used were stored frozen in order to keep the titer stable until administration during the study.

As the liquid formulation of GSK's HRV vaccine is not licensed in the US, the lyophilized formulation of the vaccine was used as a control in all phase III studies as part of the PCV-free development plan.

Study Overview

• Status: Completed
• Conditions: Infections, Rotavirus
• Intervention / Treatment: Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine; Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine

• Study Type: Interventional
• Enrollment (Actual): 1351
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1V 4G2
    • GSK Investigational Site
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • GSK Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3S 2N6
      • GSK Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3K 6R8
      • GSK Investigational Site
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • GSK Investigational Site
    • London, Ontario, Canada, N5W 6A2
      • GSK Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • GSK Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • GSK Investigational Site
• Hong Kong
  • Pokfulam, Hong Kong
    • GSK Investigational Site
  • Shatin, Hong Kong
    • GSK Investigational Site
• Taiwan
  • Changhua, Taiwan, 500
    • GSK Investigational Site
  • Kaohsiung City, Taiwan, 83301
    • GSK Investigational Site
  • Taipei, Taiwan, 100
    • GSK Investigational Site
  • Taipei, Taiwan, 104
    • GSK Investigational Site
• Turkey
  • Eskisehir, Turkey, 26040
    • GSK Investigational Site
  • Izmir, Turkey, 35340
    • GSK Investigational Site
  • Kayseri, Turkey, 38030
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35235
      • GSK Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80922
      • GSK Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40291
      • GSK Investigational Site
  • Maryland
    • Frederick, Maryland, United States, 21702
      • GSK Investigational Site
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721-1735
      • GSK Investigational Site
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • GSK Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68516
      • GSK Investigational Site
    • Lincoln, Nebraska, United States, 68504
      • GSK Investigational Site
    • Lincoln, Nebraska, United States, 68522
      • GSK Investigational Site
  • New Jersey
    • East Orange, New Jersey, United States, 07108
      • GSK Investigational Site
  • New York
    • Syracuse, New York, United States, 13210
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • GSK Investigational Site
    • Fairfield, Ohio, United States, 45014
      • GSK Investigational Site
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • GSK Investigational Site
  • Utah
    • Draper, Utah, United States, 84020
      • GSK Investigational Site
    • Murray, Utah, United States, 84107
      • GSK Investigational Site
    • Orem, Utah, United States, 84057
      • GSK Investigational Site
    • South Jordan, Utah, United States, 84095
      • GSK Investigational Site
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All subjects must satisfy all the following criteria at study entry:

• Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.

Exclusion Criteria:

Medical conditions

• Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS).
• Very prematurely born infants (born ≤28 weeks of gestation).
• 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 (no laboratory testing required).
• Hypersensitivity to latex.
• Major congenital defects or serious chronic illness, as assessed by the investigator.
• Previous confirmed occurrence of Rotavirus Gastroenteritis (RV GE).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
• History of Severe combined immunodeficiency (SCID). Prior/Concomitant therapy
• Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 1), or planned use 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 and ending 30 days after the last dose of study vaccine administration, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, and other licensed routine childhood vaccinations.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Administration of immunoglobulins and/or any blood products from birth or planned administration during the study period.
• Chronic administration (defined as more than 14 days in total) 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.
• Previous vaccination against RV. Prior/Concurrent clinical study experience
• 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 (drug or medical device).

Other exclusions

• Child in care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRV PCV-free Liq Group; Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) porcine circovirus (PCV)-free vaccine in liquid formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used.	Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine; 2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.
Active Comparator: HRV Lyo group; Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries.	Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine; 2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination	Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (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 AE regardless of intensity grade or relation to study vaccination.	During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1)
Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination	Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (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 AE regardless of intensity grade or relation to study vaccination.	During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2)
Number of Subjects With Any Unsolicited AEs	An unsolicited AE is defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment, and 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 symptoms. Any = occurrence of AE regardless of intensity grade or relation to study vaccination.	During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2)
Number of Subjects With Any Serious Adverse Events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination.	Throughout the study period (from Day 1 up to Month 7 or Month 8)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Actual): November 30, 2020
• Study Completion (Actual): November 30, 2020

Study Registration Dates

• First Submitted: May 15, 2019
• First Submitted That Met QC Criteria: May 15, 2019
• First Posted (Actual): May 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: February 25, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: HRV; Healthy infants; Rotarix; Liquid formulation; Lyophilized formulation; Human rotavirus vaccine; PCV-free; Porcine circovirus-free
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 208236; 2018-001986-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No