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

• ClinicalTrials.gov Identifier: NCT03954743
• Recruitment Status: Completed
• First Posted: May 17, 2019
• Results First Posted: June 18, 2021
• Last Update Posted: March 10, 2022
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Infections, Rotavirus	Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine; Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1351 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Data were collected in an observer-blind manner. By observer-blind, it is meant that during the study period, the vaccine(s) recipient and those responsible for the evaluation of any study endpoint (e.g. safety and reactogenicity) were all unaware of which vaccine was administered.
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: July 19, 2019
• Actual Primary Completion Date: November 30, 2020
• Actual Study Completion Date: November 30, 2020

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination [ Time Frame: During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1) ]
   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.
2. Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination [ Time Frame: During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2) ]
   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.
3. Number of Subjects With Any Unsolicited AEs [ Time Frame: During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2) ]
   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.
4. Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: Throughout the study period (from Day 1 up to Month 7 or Month 8) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 6 Weeks to 12 Weeks (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

GSK Investigational Site

Birmingham, Alabama, United States, 35235

United States, Colorado

GSK Investigational Site

Colorado Springs, Colorado, United States, 80922

United States, Kentucky

GSK Investigational Site

Louisville, Kentucky, United States, 40291

United States, Maryland

GSK Investigational Site

Frederick, Maryland, United States, 21702

United States, Massachusetts

GSK Investigational Site

Fall River, Massachusetts, United States, 02721-1735

United States, Michigan

GSK Investigational Site

Bingham Farms, Michigan, United States, 48025

United States, Nebraska

GSK Investigational Site

Lincoln, Nebraska, United States, 68504

GSK Investigational Site

Lincoln, Nebraska, United States, 68516

GSK Investigational Site

Lincoln, Nebraska, United States, 68522

United States, New Jersey

GSK Investigational Site

East Orange, New Jersey, United States, 07108

United States, New York

GSK Investigational Site

Syracuse, New York, United States, 13210

United States, Ohio

GSK Investigational Site

Cincinnati, Ohio, United States, 45245

GSK Investigational Site

Fairfield, Ohio, United States, 45014

United States, Oregon

GSK Investigational Site

Corvallis, Oregon, United States, 97330

United States, Utah

GSK Investigational Site

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

United States, Virginia

GSK Investigational Site

Charlottesville, Virginia, United States, 22902

Canada, Alberta

GSK Investigational Site

Calgary, Alberta, Canada, T3B 6A8

Canada, British Columbia

GSK Investigational Site

Surrey, British Columbia, Canada, V3S 2N6

Canada, Nova Scotia

GSK Investigational Site

Halifax, Nova Scotia, Canada, B3K 6R8

GSK Investigational Site

Truro, Nova Scotia, Canada, B2N 1L2

Canada, Ontario

GSK Investigational Site

Brampton, Ontario, Canada, L6T 0G1

GSK Investigational Site

London, Ontario, Canada, N5W 6A2

GSK Investigational Site

Sarnia, Ontario, Canada, N7T 4X3

Canada, Quebec

GSK Investigational Site

Montreal, Quebec, Canada, H3T 1C5

Canada

GSK Investigational Site

Québec, Canada, G1V 4G2

Hong Kong

GSK Investigational Site

Pokfulam, Hong Kong

GSK Investigational Site

Shatin, Hong Kong

Taiwan

GSK Investigational Site

Changhua, Taiwan, 500

GSK Investigational Site

Kaohsiung City, Taiwan, 83301

GSK Investigational Site

Taipei, Taiwan, 100

GSK Investigational Site

Taipei, Taiwan, 104

Turkey

GSK Investigational Site

Eskisehir, Turkey, 26040

GSK Investigational Site

Izmir, Turkey, 35340

GSK Investigational Site

Kayseri, Turkey, 38030

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

  Study Documents (Full-Text)

Documents provided by GlaxoSmithKline:

Study Protocol  [PDF] March 30, 2020

Statistical Analysis Plan  [PDF] October 15, 2020

More Information

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT03954743
• Other Study ID Numbers: 208236; 2018-001986-18 ( EudraCT Number )
• First Posted: May 17, 2019
• Results First Posted: June 18, 2021
• Last Update Posted: March 10, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• 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
• 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.
• URL: https://clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:

HRV; Lyophilized formulation; Liquid formulation; Human rotavirus vaccine; Rotarix; Healthy infants; PCV-free; Porcine circovirus-free

Additional relevant MeSH terms:

Rotavirus Infections; Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs